As the cost of healthcare in the United States crosses $3 trillion and cancer care approaches $150 billion annually, there is a growing public discourse on strategies to mitigate healthcare expenditures.

 Commercial payers, government agencies, and in particular, HHS, have begun piloting value-based reimbursement strategies to see how these perturbations might encourage the evolution of clinical practice and care delivery towards a value-based, alternative payment model (APM). The Center for Medicare and Medicaid Innovation (CMMI) Oncology Care Model (OCM)—proposed, and now active, in 196 predominantly community oncology practices across the country&mdash;will be particularly important, both due to the large number of eligible participants, the complexity of the program design,

 and the wealth of data that will be generated and shared between the payer (CMS) and the participating practices. If this program is successful at reducing Medicare program expenditures, while preserving or improving the quality of cancer care for beneficiaries, it likely will have a profound impact on how cancer care is paid for in the future by both government and commercial payers. 

  APMs that incentivize reductions in the total cost of cancer care (like the OCM) will encourage providers to focus on 2 of the largest categories of spend: avoidable hospital admissions and variations in treatment protocols, with a particular focus on clinical pathways and drug costs. While no drugs are singled out in the OCM model, the rapid increase in the use of immuno-oncology (I-O) agents—programmed death-1 (PD-1) and now programmed death ligand-1 (PD-L1) inhibitors&mdash;in oncology suggests that the expanding use of these agents will provide specific challenges to practice success in this program, and will likely present both operational and moral challenges for physicians attempting to succeed in the OCM.

The Opportunity Offered by I-O in 2016 and Beyond

In recent years, a deeper understanding of how the immune system works, and how cancer disarms typical immune effector functions has led to advances in ways to improve the function of specialized immune cells, called T cells.

 While many strategies are under development, this review will focus on antibodies that bind chimeric T-lymphocyte associated  protein 4 (CTLA-4), PD-1, or PD-L1 in such a way that it interferes with the binding of these cell surface proteins with their natural ligands.

 Vaccines, chimeric antigen receptor (CAR)-T cells, and small molecules that interfere with or augment other immune functions will pose similar challenges in the future, but still require further development and will not be discussed further, except to emphasize that in toto the development of I-O agents, either alone or in combination strategies, will likely dominate therapeutic advances in oncology for the next 10 years.  

CTLA-4, PD-1, and PD-L1—Targeted Agents 

Antibodies that bind CTLA-4 (ipilimumab), PD-1 (nivolumab and pembrolizumab), and PD-L1 (atezolizumab) successfully reactivate an exhausted or deactivated immune response.

 Once reactivated, some tumors will demonstrate an expansion of activated immune cells within the tumor with rapid, cancer cell destruction. Single-arm and randomized studies in melanoma, lung cancer, renal cell carcinoma, head and neck cancer, bladder cancer, and Hodgkin’s disease have demonstrated clinical activity of many of these agents.

 While the activity in Hodgkin’s disease and melanoma has been dramatic, and in the case of melanoma, often very durable (measured in years), the findings in solid tumors have demonstrated a few key themes as reviewed in 

What is most intriguing is not the response rate associated with I-O, instead the tail of the survival curve (

). In essentially all the studies that used I-O agents, there is a subset of 10% to 20% of patients who demonstrate durable responses with marked clinical improvement persisting well more than a year after treatment. Some studies with longer follow-up have demonstrated multi-year responses.

 Durable responses are distinctly unusual in patients treated with standard chemotherapy or molecularly targeted agents that inhibit nonimmune targets.  

For patients with advanced cancers being treated with palliative (noncurative) intent, despite the wealth of data suggesting a very guarded prognosis, their primary question is “can my cancer be cured?” or as a compromise “can my cancer be treated so I can live a lot longer?” If I-O provides hope for multi-year and perhaps decade-plus remissions, even if that likelihood is low (say 10%), all patients will want a chance at winning on what has been described as “an I-O lottery.” Further, patient and physician preference for I-O is also influenced by the fact that, compared with many alternative therapies, I-O is less toxic for most patients than chemotherapy. Thus, PD-1 inhibitors gain a strong acceptance based on slightly superior response rates, the important “tail of the curve” comprised of the I-O lottery winners,” and decreased toxicity.   

I-O at the Center of the Clash of Innovation and Value

The management of cancer is complex and expensive. The use of sophisticated imaging, molecular diagnostic tests along with the frequent use of expensive therapeutic modalities including surgery, radiation, chemotherapy, biologics, and supportive drugs can easily lead to courses of therapy that exceed $100,000 in the first year of a cancer diagnosis. Similar or even greater expenses are often also seen in the last year of life for those patients who can’t be offered curative therapy. Cancer spending was estimated to be $130 billion in 2010 and is expected to be between $170 billion and $180 billion in 2020.

demonstrates the rough breakdown of annualized costs from patients with cancer.  As seen in the graph, a significant expense is the office-based drug costs. Cancer drugs (oral plus intravenous) and hospitalization make up almost two-thirds of the spend, thus, it will be hard to ignore these categories of expense as the provider community is challenged to participate and ultimately take risk in the quest to decelerate the increasing spend on cancer care. A special area of focus will be the PD-1 and PD-1—inhibitors, which have gone from investigational agents to one of the top 5 oncology drugs in terms of costs in the community, in the last 2 years, with year-over-year growth of 300%. With the recent approval of pembrolizumab in a subset of individuals with newly diagnosed metastatic lung cancer, the country’s most common lethal malignancy, it is likely even more patients will be getting this therapy with their time on therapy being potentially longer. In addition, it is likely that in 2017 we will see additional inhibitors of PD-1 and PD-L1 approved, and potentially the combination of these agents with ipilimumab or other CTLA-4–binding agents. By some estimates, I-O drugs already represent 18% of the drug spend. As the principal APM in cancer, the OCM is due to pilot through 2021, and it is likely that I-O drugs will represent the principal driver of cancer drug costs, which as a class may represent 50% of the oncology drug spend towards the end of the OCM pilot trial. 

I-O innovation arrives concurrently with the rapid roll-out of APMs. Both government and commercial payers are exploring novel, alternative payment strategies that will compel physicians to pay considerably more attention to the total cost of the cancer treatment and evaluation they prescribe. As the average age of cancer incidence is adults in their 60’s, Medicare is the single most dominant payer of cancer expenses in this country. Thus, it is instructive to consider the Medicare Access and CHIP Reauthorization Act (MACRA) and the OCM to illustrate how these programs will impact oncology care and the oncology practitioner.

In 2015, Congress repealed a long-standing CMS program called the Sustainable Growth Rate program and replaced it with MACRA, which includes a performance-based adjustment to a practice’s Medicare payment, under the acronym of MIPS (Merit-based Incentive Payment System). This program, which took effect in January 2017, requires the submission of quality data from the practices along with claims data (from CMS). Practices will be scored on clinical quality metrics, cost of care, and practice improvement. CMS will provide 0.5% annual increases in total payouts through 2019 and will then keep payouts flat (budget neutrality), but will rank practices based on the above metrics to pick winners and losers. Those who outperform their peers will receive bonus payments of up to 9% while those that significantly underperform will see their payments drop by 9%. Of note, a well-run oncology practice in the community might expect a margin of 12% to 18% of revenue; thus a 9% gain or loss will have extraordinary effects on the bottom line of the clinic, especially when one considers that overachieving on quality metrics might take incremental investments. Practices that invest wisely and over-perform can expect at least some financial reward. Those that lack efficiency, scale, or a focus on quality will likely face extreme challenges in the MACRA-MIPS environment. Data will be sent to CMS in 2017, with bonuses or penalties being delivered in 2019.

A practice can gain additional benefits and risks by entering an advanced APM such as the “2-sided risk” version of OCM, which includes some of the same quality metrics of MACRA and MIPS along with additional responsibilities in transforming the care delivered to the patient. Practices participating in the OCM are compared with their baseline performance prior to program initiation, along with a number of adjustments and trend factors. The trend factor, still poorly defined, is proposed to correct for inflation and take into account the realization that innovation will likely increase costs. Of note, the global baseline cancer spending calculated by CMS preceded the approval of all the PD-1 and PD-L1 checkpoint inhibitors.

In healthcare, value is often defined as quality divided by cost—increasing quality and/or decreasing costs offers the chance of increasing value. Indeed, in theory, one could still achieve an increase in value with higher costs if the quality of care improved dramatically. Economists often refer to value from the patient perspective. Measuring cost, the denominator of the value equation, is not as simple as it seems because it includes not just the direct cost of care, but also opportunity costs for the patient from lost time at work, or perhaps for the caregiver who left work to support the patient. Quality is an order of magnitude more challenging to convert into a number. From the patient’s perspective, quality could include several concerns:

Obviously, how an individual patient scores these issues, numerically, is a daunting proposition and likely is very individualized. One patient might emphasize that value centers predominantly around their ability to live independently, while another might ascribe value just to surviving to a key milestone such as a wedding or delivery of a grandchild. It should be apparent that these types of value determinations are qualitative and precise measurement is aspirational. As a poor substitute, organizations have proposed various statistical standards such as cost per quality-adjusted life-years that a certain therapy provides, or costs to prevent a single death.

Within the US Oncology Network—a national collection of 1400 cancer caregivers including over 800 medical and gynecologic oncologists&mdash;much of the decisions around drug use are guided by well-conducted and peer-reviewed clinical trials that are vetted by the National Comprehensive Cancer Network, and then further scrutinized by a Pathway Committee of the US Oncology Network. Selected drug regimens are defined by a combination of clinical efficacy and cost. Typically, costs are simply the drug costs since there is little data of costs of supportive care, in particular the likelihood that a specific regimen will require urgent care, emergency care, or hospitalization. Developing such databases personalized to an individual’s age, gender, comorbid disease, and performance status is an important goal for the future.

Ethical Issues of Society Versus the Individual and Models Around the Drug Value Proposition

The I-O agents, specifically, the PD-1 and PD-L1 inhibitors, pose a particular set of challenges. Although sweeping generalizations are hazardous, a high-level summary of the data around these agents is as follows:

		Compared with chemotherapy or other targeted agents, I-O agents are marginally more effective in many patients, and moderately to markedly more effective in a small minority of patients. 

		These agents are, in general, less toxic than most chemotherapy agents used in late- stage cancer. 

		I-O agents are moderately or markedly more expensive than standard chemotherapy.

		There is little guidance in the current literature on how long to continue these agents in patients with durable responses or how much emphasis to place on PD-L1 tumor expression. 

Thus the cost calculation of the value equation is high; however, since the toxicity is less (on average) than chemotherapy and the clinical outcome is improved, the quality (numerator) of the value equation is also higher. However, its impact on the overall value depends on how much an individual patient benefits, which of course is hard to predict a priori.

To make issues a bit more complicated, alternative payment models, in general, and the OCM in particular, doesn’t really reward value as described above. It does include quality metrics, but doesn’t include response, survival, or toxicity. The calculation of shared saving that would be delivered to the practice is equal to a quality score multiplied by cost saving score. Consider, as an example, a practice that doubled its quality score from 50 to 100 while its healthcare costs increased 10%. In this hypothetical case there was a marked improvement in quality and perhaps even survival, simultaneously with an increase in costs. While the improvement in quality would exceed the cost increase (and thus improved “value”), the cost-saving equation would yield no financial return for the practice (reward in the OCM = quality score x cost savings). In the event the practice made significant financial investment to transform clinical care through investment in information technology, staff, and processes, they could easily have overspent their monthly management fee. This highlights an important discordance with value and shared savings that dominates APMs.

In reality, while quality improvements are important, the dominant factor in the model is a reduction in costs. This puts the physician in a challenging position, especially in a society with direct-to-consumer marketing and the increasing awareness and hype around the potential of immunotherapy. For a patient with recurrent cancer of the lung, kidney, bladder, head and neck region, Merkel cell tumor, melanoma, or Hodgkin’s disease, there is a growing body of literature that supports considering I-O agents. There are currently hundreds of clinical trials evaluating PD-1 and PD-L1 agents alone or in combination with other I-O agents. It is almost certain that during the tenure of the OCM project, PD-1 and PD-L1 agents will gain approval in many additional malignancies, including in patients with locally advanced or newly diagnosed metastatic disease as was recently witnessed in melanoma, and a subset of non—small cell lung cancer patients.

 In an environment that is without fiscal restraints, patients were offered such therapies with risk falling to the payer (government, insurer, employer, and to a lesser extent the patient).

In the OCM world, such behavior adds risk to the participating practice. In addition, in the setting of higher patient co-payments, the patient now also bears more of the risk. Bearing risk in community oncology practices translates into risks to personal income and the practice’s vitality, challenging the physician to weigh personal interests against patient interests. While capitated contracts and risk-bearing contracts have existed in the past, particularly in healthcare systems and primary care practices, the scale of the OCM and the prices associated with these agents provide very broad risk corridors not typically seen in primary care or pediatrics practice. 

Challenges in Delivering I-O Therapy Rationally

It is a physician’s obligation to deliver therapy that will benefit the patient, and the current data supporting I-O therapy provides compelling evidence that it should be part of the therapeutic armamentarium in a variety of malignancies. Unfortunately, we are missing several important pieces of data that might help physicians deliver these therapies rationally. 

 lists questions that might help moderate the costs of I-O. 

While there is an unprecedented number of I-O trials actively enrolling patients, essentially all these trials are looking for expanded use of PD-1, PD-L1, or CTLA-4—binding agents or novel I-O agents, either alone or with the approved agents. These trials, if positive, will only accelerate the rise of I-O use and costs in cancer care.

Ideally, a society should support an environment of innovation that improves the lives of its citizens, and simultaneously permits the astute use of its limited resources. Improving the value of the care we deliver to cancer patients is important. The shift to value-based care, concurrent with the innovations in immunology and the rapidly growing indications for I-O agents, will create significant challenges for the physicians and healthcare systems in the near term. Community-based oncologists will need to be particularly savvy in meeting the operational and financial demands of clinical transformation prescribed by value-based care, while maintaining the financial viability of their practices. Finally, manufacturers of I-O agents should share the responsibility of supporting value-based pricing. The market is becoming more crowded with duplicate I-O agents, and competitive pricing will lower the tension that these treatments inflict on the value equation.

	Michael V. Seiden, MD, PhD, is chief medical officer, McKesson Specialty Health and The US Oncology Network.

	Marcus Neubauer, MD, is medical director, McKesson Specialty Health.

	Diana Verrilli is vice president, Payer and Revenue Cycle Services, McKesson Specialty Health.

		Mariotto AB, Yabroff KR, Shao Y, Feuer EJ, Brown ML. Projections of the cost of cancer care in the United States: 2010-2020. 

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		Boussiotis VA. Molecular and biochemical aspects of the PD-1 checkpoint pathway. 

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		Postow MA, Chesney J, Pavlick AC, et al. Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. 

. 2015;372(21):2006-2017. doi: 10.1056/NEJMoa1414428.

		Garon EB, Rizvi NA, Hui R, et al ; KEYNOTE-001 Investigators. Pembrolizumab for the treatment of non-small-cell lung cancer. 

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Articles

Evidence-Based Oncology

The shift to value-based care, concurrent with innovations in immune-based care, will create challenges in oncology. What should be the physician and manufacturer responsibility during these changing times?

Advanced APMs and the Emerging Role of Immuno-Oncology Agents: Balancing Innovation and Value

Immunotherapy is one of the fastest growing areas of cancer research. The Cancer Moonshot 2020 Program calls for the creation of a Cancer Immunotherapy Translational Science Network to develop and implement immune-based approaches for preventing and treating adult and pediatric cancers.

 There are more than 500 open immunotherapy trials listed on ClinicalTrials.gov,

 and the list of immunotherapy drugs, as well as the cancers that are approved to treat, keeps growing.

Currently, not all cancer patients are aware that immunotherapy, either through a clinical trial or as a prescribed treatment, might be one of their options. Those who do, may not be fully aware of how immunotherapy works or of the short- and long-term side effects they may experience. Additionally, as with other oncology treatments, patients may not be aware of the total cost of these new treatments or the patient-assistance programs that can help to offset those costs.  

Methods Used to Gather Patient Insights on Immunotherapy

Quantitative data were obtained from an online survey and analysis of 367 evaluations of in-person immunotherapy workshops. Qualitative data and insights were gathered from a 2-day Immunotherapy Patient & Caregiver Summit.  

The Cancer Support Community (CSC) is the largest professionally led nonprofit network of cancer support worldwide, reaching more than a million people annually. CSC is dedicated to ensuring that all people impacted by cancer are empowered by knowledge, strengthened by action, and sustained by community. These aims are met through direct service delivery, research, and advocacy. CSC’s educational programs, which incorporate and reflect research and advocacy, are designed to help cancer patients make treatment decisions that align with their goals and values (

 (FSAC) series provides an in-depth coverage of topics relevant to those affected by cancer that are not otherwise available in a comprehensive format.

 The series—delivered through in-person workshops, print publications, online content, webinars, and a radio show&mdash;addresses topics such as cancer treatments and side effects and coping with the cost of care. Series topics are based on identified areas of need.  

An online survey that CSC conducted, in 2014, found that 34.8% of cancer survivors knew the term immuno-oncology and 64.9% had heard of immunotherapy. The survey also showed that 84% of respondents were interested in learning more about these topics. In response, CSC developed 

FSAC: Your Immune System and Cancer Treatment

 for cancer patients and their caregivers. Thus far, FSAC has developed educational content on immunotherapy as a cancer treatment and immunotherapy options by cancer type, which is accessible on the CSC website (www.CancerSupportCommunity.org/immunotherapy); 4 print/downloadable booklets; 3 webinars; 22 in-person workshops; and a 2-day immunotherapy patient and caregiver summit.   

 workshops provide an opportunity for patients and caregivers to obtain comprehensive information about immunotherapy, as well as learn how to communicate with their healthcare team about immunotherapy treatment options. In 2014-2015, local CSC/Gilda’s Clubs across the United States hosted 532 attendees at 11 in-person immunotherapy workshops. Of these 532 attendees, 367 completed evaluations that included personal demographics and self-reported pre- and postworkshop comparisons—72.5% of respondents were individuals with cancer, 20.5% were caregivers, and 5.8% were healthcare professionals. After the workshop, most respondents felt better equipped to discuss potential side effects (86.8%), have a conversation with their healthcare provider on treatment options (91.5%), and make treatment decisions in tandem with their doctors (87.9%). These findings were presented at the 2016 American Psychosocial Oncology Society Annual Conference.

Strikingly, even though many workshop attendees described themselves as “partners” with their healthcare team when making decisions, many had no idea whether immunotherapy was an option for them. These and other findings reaffirmed the need for cancer patients to receive clear, relevant, and comprehensive information about immunotherapy. The findings also underscored the importance of promoting proactive communication between patients and their healthcare team about whether or not immunotherapy is, or might soon be, a treatment option.  

Insights From Patient and Caregiver Summit

In November 2016, CSC held a 2-day Immunotherapy Patient & Caregiver Summit specifically for cancer patients and caregivers who have received immunotherapy treatments. The summit provided a unique opportunity for immunotherapy patients to share their experiences and for CSC to identify specific needs and concerns of patients who are on these treatments. The summit was attended by 30 individuals—18 patients and 12 caregivers from throughout the United States who had been selected through an online application process. Eight of the patients had blood cancers, 10 had solid tumors.    Even after receiving treatment, patients and caregivers remain confused about what is immunotherapy and whether they have received immunotherapy or other novel therapies.

Tellingly, over half of the patients and caregivers who applied to participate in CSC’s immunotherapy summit did not understand that they were ineligible for the summit because they or their loved one had 

 been treated with an immunotherapy.    CSC gained insight into how cancer patients and caregivers perceive the challenges, and hope, unique to immunotherapy from summit participants by through focus groups, written comments, and discussions in workshops on topics such as side effects, self-advocacy, and storytelling. The insights gathered also helped to identify gaps in immunotherapy patient education. Before arriving at the summit, the 30 participants were asked to review several of CSC’s

 immunotherapy materials. Utilizing a focus group format, participants also provided specific feedback on these materials.    

Many of the participants had received or were receiving immunotherapy through clinical trials. Most knew very little, and some knew nothing, about immunotherapy before starting treatment. Discussions revealed that some patients and caregivers were not initially aware that immunotherapy differed from, and was not a type of, chemotherapy, while others didn’t know they would be receiving an infusion. For some, treatment also entailed learning to navigate the multiple campuses and buildings that comprise many large cancer centers. Patient experience was also complicated by the fact that many accessed these new treatments through clinical trials, which made it difficult for them to learn from other people’s experiences on treatments and side effects.   

Side effects alone posed a unique concern. Some participants feared that telling their healthcare team about the side effects they were experiencing would result in their having to withdraw from an immunotherapy trial that was their only treatment option. This concern appeared to be compounded by the fact that patients and caregivers expected immunotherapy to be easier to tolerate than chemotherapy and to result in fewer side effects. This left them unprepared for the severe flu-like symptoms, overwhelming exhaustion, diarrhea, sleep disturbances, and endocrine problems many experienced. It also left them concerned about what these more severe side effects might portend.  

After receiving immunotherapy, most patients and their caregivers understood the need for managing side effects quickly. Throughout the summit, patients and caregivers expressed a need for more detailed educational content on side effects and which symptoms they should immediately report to their healthcare team. Patients reported that the drug information they did receive was hard to understand and did not make a distinction between symptoms of their disease and symptoms that may be side effects of their treatment.  

Patients and caregivers reported high levels of distress associated with balancing their life, an advanced-stage disease, and treatment. Only a few patients and caregivers reported being offered psychosocial resources to mitigate their distress. Patients also reported anxiety about living with uncertainty, as well as some cognitive distress because they did not “look sick” on immunotherapy while they were often very fatigued and medically fragile.   

Another important theme that emerged from the summit was the need for patients and caregivers to have more clarity on how immunotherapy might impact other aspects of routine care from a primary care provider, another specialist, or in an emergency room setting. For example, it surprised patients that their other health providers might not know that they had to avoid live vaccines. To address this need, patient and provider educational materials and communication tools must be developed that guide patient and provider communication on what drugs, vaccines, or treatments can and cannot be used by cancer patients on immunotherapy.  

No discussion of immunotherapy would be complete without mentioning the total cost of new cancer treatments. The summit underscored the high degree of distress patients experience around the cost of cancer in general, and immunotherapy treatments, in particular, even within the context of a clinical trial. As many have previously noted, the total annual cost of care for immunotherapy and other novel treatments can exceed $100,000.

 The patient burden, through co-payments and co-insurance, can be tens of thousands of dollars. When patients do not have access to or do not know how to access patient assistance programs, these costs can quickly contribute to what is now widely referred to as the financial toxicity of cancer care.

CSC’s Support Services for Patients and Caregivers

Frankly Speaking About Cancer Clinical Trials

 program (www.CancerSupportCommunity.org/ClinicalTrials). This landmark education series aims to build awareness among patients and caregivers about the importance of clinical trials as a viable treatment option. This program will be especially important for patients as the number of new, experimental immunotherapy treatments increases.  

CSC provides services that can help patients and caregivers understand and manage their treatment, mitigate distress, and get help assessing and managing cancer costs. These include:

. Education Programs and Information Created for Cancer Patients and Caregivers (see PDF at the end of the article).

Analysis of survey data and immunotherapy workshop evaluations, along with insights from CSC’s Immunotherapy Summit demonstrate that patients, caregivers, and even primary care and emergency healthcare providers need education on immunotherapy treatment. This education needs to be bolstered with patient—provider communication support and tools to ensure that patients, caregivers, and all healthcare team members are working together to improve patient health. Finally, patients and caregivers need referrals to psychosocial support and educational resources, like those available from Cancer Support Community, to help them understand their disease and treatment, reduce distress, manage the total cost of care, and improve quality of life.    

Over the next few years, findings from clinical trials that are now underway will shed light on the increased impact of immunotherapy on cancer—from prevention through treatment. In preparation for potential advances as well as inevitable setbacks and disappointments, new content needs to be developed to help cancer patients and caregivers navigate immunotherapy treatments. CSC is very close to releasing immunotherapy content for 3 additional tumor types, material in Spanish, and video testimonials from patients and caregivers who have experienced immunotherapy treatment. Our quantitative data and qualitative insights reinforce the need for more content to be distributed to additional patients and caregivers, as well as the need for continued improvement of this content over time.  

CSC is also engaging in conversations with policy makers and other patient advocacy organizations on the impact of the total cost of these treatments on patients as our healthcare system braces for changes. This is a time in cancer care where high hopes meet unknowns. As we move forward, it will be critical to include the voices of cancer patients and caregivers in the development of new immunotherapy educational programs, as well as in finding solutions to the impact of systemic changes.

		Claire Saxton, MBA, is senior director, Education, Cancer Support Community.

		Joanne Buzaglo, PhD, is senior vice president, Research and Training, Cancer Support Community.

		Sue Rochman, MA, is contractor for Cancer Support Community as well as an independent health writer.

		Alexandra Zaleta, PhD, is director, Research, Cancer Support Community.

	E-mail: csaxton@CancerSupportCommunity.org

		The Cancer Moonshot Blue Ribbon Panel Report 2016. National Cancer Institute website. https://www.cancer.gov/research/key-initiatives/moonshot-cancer-initiative/blue-ribbon-panel/blue-ribbon-panel-report-2016.pdf. Published October 2016. Accessed December 28, 2016.

		ClinicalTrials.gov. Search Immunotherapy and Cancer. https://clinicaltrials.gov/ct2/results?term=cancer+immunotherapy&recr=Open. Accessed December 28, 2016.

		Timeline of Progress. Cancer Research Institute website. http://www.cancerresearch.org/our-strategy-impact/timeline-of-progress/timeline-detail. Accessed December 28, 2016.

		Frankly speaking about cancer. Cancer Support Community website. http://www.cancersupportcommunity.org/frankly-speaking-about-cancer. Accessed January 11, 2017.

		Amsellem M, Suarez R, Wilson C. Informing and empowering cancer patients about immunotherapy: a psychoeducational workshop addressing needs in an emerging field. Presented at: 2016 American Psychosocial Oncology Society 13th Annual Conference, March 3-5, 2016, San Diego, CA. 

		Carroll J. New immunotherapies for cancer yield exciting results but high cost. Managed Care website. http://www.managedcaremag.com/archives/2013/10/new-immunotherapies-cancer-yield-exciting-results-high-cost. Published October 2013. Accessed January 11, 2017.

		Financial toxicity and cancer treatment (PDQ)-health professional version. National Cancer Institute website. https://www.cancer.gov/about-cancer/managing-care/financial-toxicity-hp-pdq. Updated December 14, 2016. Accessed December 28, 2016.

Patients, caregivers, and providers need education on immunotherapy treatment, support in patient-provider communications as well as support in mitigating the financial impact of immunotherapy treatment.

Helping Cancer Patients and Caregivers Navigate Immunotherapy Treatment

Jae Park, MD, is a hematologist-oncologist, at the Memorial Sloan Kettering Cancer Center (MSKCC) in New York, who is leading a clinical trial using chimeric antigen receptor (CAR)-T cells in the treatment of patients diagnosed with chronic lymphocytic leukemia (CLL). Park is also a part of trials investigating CAR T-cell treatment in patients with acute lymphoblastic leukemia (ALL).

™), Park described how the treatment manipulates the body’s immune system, reviewed some of the challenges that the field is currently faced with, and predicted what the future holds for CAR-T cells.

 Can you explain the leukapheresis process that is necessary for CAR T-cell treatment?

: CAR is an artificial T-cell receptor that is genetically engineered by combining a binding domain from a monoclonal antibody that is fused to a T-cell receptor. So the chimera binds like an antibody but acts like a T cell, and that’s where the name “chimeric antigen receptor” originates. It allows the T cell to recognize and bind a tumor, just like an antibody would. It then allows a universal applicability of this type of therapy; so once you create a CAR against a specific tumor antigen, you can modify the T cells—either the patient’s own T cells or donor T cells&mdash;to express the chimeric antigen receptor, which is now reeducated or reengineered to recognize a specific tumor antigen on a cancer cell better.

Once infused into the patient, these T cells traffick to the site of the tumor and they start eradicating the tumor cells. That’s the basic mechanism by which CAR-T cells function.

Leukapheresis, which is sometimes called apheresis, is the process of collecting white blood cells (WBCs). The process is very similar to that of platelet donation—the patient is hooked up to a machine with 2 catheters, 1 in each arm. The machine filters and collects only the WBCs while the rest of the blood components are returned to the other arm. The entire process can last between 2 and 4 hours, the rate-limiting steps being the rate of blood flow and the volume of blood that needs to be collected.

Autologous or patient-derived T cells are the most commonly used form of CAR-T cells, so the patients are the ones who undergo leukapheresis.

Cytokine-release syndrome, a typical reaction to CAR T-cell treatment, can drain a patient—both physically and emotionally. Can you explain why the patient’s immune system generates this massive response? How is it typically managed?

 Cytokine-release syndrome, or CRS as it is commonly called, is the body’s response to the T cells attacking the tumor cells. As the T cells are getting stimulated, and expand upon recognition of cancer cells, they release inflammatory proteins called cytokines—this is our body’s typical immune response to fight off infection. Just as a viral or bacterial infection results in fever or issues with breathing or blood pressure, where the T cells release pro-inflammatory cytokines as a way to alert or recruit the body’s endogenous immune cells to fight the infection.

Similarly, in this case, as the T cells are infused and are trafficked to the site of the tumor, they recognize the cancer cells, are activated, and they release pro-inflammatory cytokines. The body’s reaction to this is the patient gets a high fever, and experiences low blood pressure or breathing difficulties. If the reaction is very severe, the patient may need to be managed in an intensive care unit.

CRS is typically managed using anti-inflammatory agents—one very specific way of treating these patients is by using an IL-6 inhibitor called tocilizumab, which has been approved for the treatment of rheumatoid arthritis. IL-6 levels are elevated during CRS, so by blocking this specific cytokine, you can dramatically, and very quickly, reverse the patient’s symptoms. If this treatment is not sufficient, then we do use corticosteroids&mdash;a more general way to suppress the overall immune response. And these are mostly reversible. So a patient may get sick for a time with high fever and such, but once they receive the treatment, these symptoms reverse very quickly. However, CRS can be fatal so special attention is needed to prevent and effectively manage this unique side effect.

In your experience, are all patients equally susceptible to CRS following CAR-T treatment?

We do see a range in the severity of patient responses. We have developed a grading system—mild CRS or severe CRS&mdash;to document the severity of patient response. Sometimes, we can predict how severe CRS may be in a patient, which is dictated by the patient’s disease burden. A higher disease burden means more antigens for the T cells to interact with, they get activated faster and expand to a greater degree, and more severe the CRS. So it really depends on how much disease you have, what type of T cells, and what dose of T cells is infused&mdash;which matters as well.

So there’s a host of factors that can affect the degree of CRS.

Which types of cancers has this treatment been tried in, overall, and at MSKCC in particular?

At MSKCC, we have used CAR T-cell treatment in patients with ALL, CLL, and for non-Hodgkin’s lymphoma, including diffuse large B-cell lymphoma. We also have a trial for solid tumors, specifically for mesothelioma, which is a type of lung cancer, for breast cancer, and for ovarian cancer. So these trials treating these disease types are currently enrolling patients.

We also have a pediatric ALL trial that is treating younger patients with CAR-T cells.

CAR T-cell treatment is very expensive. When do you anticipate this treatment to be used in mainstream cancer care?

Right now, the treatment is expensive, but hopefully the cost of treatment with CAR-T cells will come down. Compared with a transplant or where you need repetitive treatments with a drug such as an oral targeted drug, the advantage with CAR T-cell treatment is that 1 infusion of the drug can induce a great degree of remission. So, although the upfront cost may be high, downstream costs associated with this treatment likely decrease over time.

This form of T-cell treatment could be considered an ‘N-of-1’ trial. Will the FDA evaluate this treatment differently, compared with the regular drug approval process?

I think the FDA is viewing this therapy quite favorably because they recognize that for some of the diseases that are being studied, there currently are no good alternatives for treatment. There are some regulatory processes involved, because this treatment is categorized as a gene therapy due to the use of a retroviral or lentiviral vector for modifying the genetically engineered T cells. But the treatment has already received a breakthrough treatment designation for ALL and is close to being approved, as long as its efficacy and safety are confirmed in the ongoing large phase II clinical trials. 

Are combination trials of CAR-T cells with immune checkpoint inhibitors being planned in the near future?

CAR T-cell therapy, especially in ALL, is very effective and patients can get into remission 80% to 90% of the time, which is why we are so excited about this treatment. But it’s not perfect, and not all patients benefit from it, and even after the initial respons, relapses do occur. So there’s more work needed to overcome some of these challenges, and combining CAR T-cell treatment with one of the immune checkpoint inhibitors might be one way. It could help prolong the immune response, prolong the persistence of the T cells, and hopefully prolong the duration of response. 

These treatments are being evaluated at some of the centers around the country. Currently, we do not have enough data to draw conclusions on whether the combination of CAR-T cells with immune checkpoint inhibitors will be effective or whether it would result in more side effects. There are some safety mechanisms and management guidelines with these type of trials, but it’s definitely a natural next step that we are currently exploring. 

Next-generation CAR-T cells are also being explored in clinical trials—these cells are made stronger even without the immune checkpoint inhibitors. 

What is your prediction about where the future lies for CAR-T cells in oncology care?

We are obviously very excited about the tremendous impact of immunotherapy in cancer care. Moving from chemotherapy, which is very nonspecific, to oral targeted treatments that target specific pathways—cancer cells do become resistant to these treatments. With immunotherapy, we are not targeting any particular signaling pathway; rather we are manipulating the body’s immune system to better recognize and kill cancer cells.

So, the future, I think, is very bright and we are very close to getting this therapy approved in patients with ALL, using CD19-targeted CAR T-cells. We do have a lot of unanswered questions, such as whether treatment efficacy will remain the same with solid tumors and if not, whether we can improve efficacy with next-generation CARs or by combining the treatment with immune checkpoint inhibitors or with oral-targeted therapy.

A lot of efforts are being invested to improve the safety and efficacy of CAR-T cells, so we do expect the emergence of better and safer therapies in the future, either in combination treatments or by further modification of CAR-T cells, to hopefully lead us to a “cure” for cancer. I believe CAR-T cells is one of the ways by which we can get there.

An oncologist provides insight on his experience with using CAR-T therapy in the clinic and his prediction for the future of this revolutionary treatment.

Q&A With Dr Jae Park on the Promise of CAR-T Cells in Cancer Care

Immunotherapy as a treatment modality for cancer has been studied for over 5 decades. However, with the recent surge in new treatment options, immunotherapy seems to have come of age. An increasing number of immunotherapy agents have been approved for multiple tumor types over the past few years, bringing the promise of a more effective and less toxic form of cancer treatment. However, as these agents are increasingly making their way from the bench to the clinic, we as community oncologists will have to learn how costly new immunotherapy agents will be incorporated into the changing reimbursement landscape.

The cost of cancer care in the United States is growing rapidly and currently represents 5% of total healthcare spending.

 Costs are estimated to grow from $158 billion to $173 billion by 2020, reflecting an increase of 27% to 39%. Drug costs are a key driver of oncology spending, including immunotherapy and targeted agents—the per patient per year spending on chemotherapy has increased from 15% to 20%. The response to rising costs by both Medicare and commercial payers has been to explore various payment models including clinical pathways, the oncology medical home model, bundled payments, and the Oncology Care Model. The overhanging question is how will these new and potentially beneficial therapies be incorporated into payment models that are designed to contain the cost of cancer care?

There is no question that those of us in community practice have seen some remarkable responses to immunotherapy. Pembrolizumab was first approved in 2015 for the treatment of metastatic melanoma based on improved overall survival (OS) and progression-free survival.

 Subsequently, nivolumab received approval for non—small cell lung cancer (NSCLC), and more recently, atezolizumab received approval for platinum-resistant metastatic bladder cancer, also based on significant survival benefit. The cost of pembrolizumab before discount is $12,500 per patient per month or approximately $150,000 per year. Similarly, both nivolumab and atezolizumab cost approximately $150,000 per year.

The Institute for Clinical and Economic Review (ICER) recently evaluated the cost effectiveness of all 3 approved immunotherapies targeting programmed death-1 (PD-1; nivolumab) or programmed death-ligand 1 (PD-L1; pembrolizumab and atezolizumab).

 The report, which analyzed the clinical benefit of each drug against cost and health-system affordability, found that that a “substantial minority” of patients had gained clinical benefit, but for those patients who did respond, there was a substantial improvement in OS. In terms of cost effectiveness, ICER estimated that atezolizumab cost $219,179 per quality-adjusted life year (QALY) gained, pembrolizumab cost $240,049, and nivolumab $415,950. The report placed a benchmark of $100,000 to $150,000 per QALY. To reach this benchmark, ICER estimated that atezolizumab would require a reduction in its wholesale acquisition price (WAC) of 31% to 53%. For pembrolizumab, the WAC would require a reduction of 39% to 61%, and nivolumab would require a reduction of 57% to 68%.  

How do we as community oncologists manage the financial burden of these costly medications in our current buy-and-bill model? The current unit cost for pembrolizumab is $4650, and for nivolumab it is $3000. As community practitioners, we need to be very diligent about obtaining preauthorization and documentation to ensure timely payment. As the indications for immunotherapies expand, the financial burden on practices is expected to substantially increase. The out-of-pocket costs associated with these treatments can also be prohibitive for many patients. Practices will need a robust financial assistance program to help with patient copayments, either through foundation programs or through the pharmaceutical companies themselves. 

Bristol-Myers Squibb started a direct-to-consumer marketing campaign for nivolumab, in 2015, that has cost approximately $125 million.

 The drug maker has stated that this aggressive direct-to-consumer approach is a way to facilitate discussions regarding immunotherapies between healthcare providers and patients.

This approach by the company has received a fair amount of criticism from academic and community oncologists, as well as patient advocates. We have definitely noticed the effects of this marketing campaign in our practice. In our experience many patients have a misconception that these therapies represent a “miracle cure.” Marketing campaigns have certainly influenced patient opinions about immunotherapy. As a community oncologist, the onus is on us to temper patient expectations about these treatments and also to bring up cost-benefit discussions with patients. 

So where are we in this age of immunotherapy? I think we would all agree that this new treatment modality has the potential to revolutionize the practice of oncology. We are now seeing immunotherapies gaining wider use in the frontline setting in both metastatic melanoma and NSCLC. However, using these new therapies in the clinic has shown that they are far from a “miracle cure.” Many patients fail to respond to immunotherapy. 

Oncology as a whole must shift away from the one-size-fits-all treatment model. As newer therapies emerge, resources must be directed to identify those patients who would actually benefit from newer treatment modalities, allowing both patients and practitioners to make more informed treatment decisions. With the expansion of big data, we in the community should anticipate a shift in focus towards patient outcomes, because in the coming years, both payers and patients will demand treatments based on value. We in the community will be on the frontline of this changing landscape. In our current structuring of oncology care, immunotherapies will not remain an affordable treatment modality in the future. 

There are several important questions that we must ask ourselves going forward, a key one being ‘How will community oncologists be able to incorporate emerging therapies and maintain financial viability?’ As I have previously mentioned, mitigating patient expectations regarding immunotherapy and honest discussions regarding the cost of these agents compared with potential benefits are a must. We also need to advocate for more research into identifying markers that would predict benefit, allowing practitioners and patients to have an informed discussion about the treatment plan. 

	Sumeet Chandra, MD, is a medical oncologist at Medical Associates of Brevard in Melbourne, Florida.

	2290 West Eau Gallie Boulevard, Suite 202

Community oncologists will be at the forefront in this emerging age of immunotherapies and will need to be strong advocates for greater information and affordability of these new and potentially groundbreaking therapies.  

		Robert C, Schachter J, Long GV, et al. Pembrolizumab versus ipilimumab in advanced melanoma. 

. 2015;372(26):2521-2532. doi: 10.1056/NEJMoa1503093.

		Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus docetaxel in advanced nonsquamous non—small-cell lung cancer. 

. 2015;373(17):1627-1639. doi: 10.1056/NEJMoa1507643.

		Institute for Clinical and Economic Review. Treatment options for advanced non-small cell lung cancer: effectiveness, value and value-based price benchmarks. Institute for Clinical and Economic Review website. https://icer-review.org/wp-content/uploads/2016/08/MWCEPAC_NSCLC_Evidence_Report_Plus_Supplement_101716.pdf. Updated October 7, 2016. Supplement October 17, 2016. Accessed December 29, 2016. 

		McCaffrey K. DTC ads for Opdivo face further backlash. MM&M website. http://www.mmm-online.com/campaigns/dtc-ads-for-opdivo-face-further-backlash/article/516023/. Published August 15, 2016. Accessed January 9, 2017.

Community oncologists will be at the forefront of using immunotherapies and will need to be strong advocates for greater information and affordability of therapies.

From Bench to Community Oncology Clinic: The Promise of Immunotherapy

	The promise of immunotherapy is fraught with challenges—with an increase in indications for these immuno-oncology (I-O) agents, healthcare providers and patients are slowly realizing the balance they must strike with I-O. At the 5th annual Patient-Centered Oncology Care

) meeting, held November 17-18, 2016, in Baltimore, cancer research advocate Debra L. Madden discussed the importance of educating patients and caregivers on the variety of adverse events associated with I-O.

	Being a systemic treatment, I-O agents provide a significant boost to the patient’s immune system, and also impact its long-term memory and duration of response, Madden told the audience. While I-O agents have the potential to benefit patients across a variety of cancer types, managing patient and family expectations on these treatments is crucial. Debra emphasized that patients should understand the limitations of this treatment. “Those who have an autoimmune disorder, have undergone an organ transplant, or need to be on steroid treatment, for example, are not ideal candidates for immunotherapy,” she said.

	Despite all the necessary exclusions and precautions, translating trial results into the clinic often yields unexpected patient responses, which makes it imperative to consider each patient on a case-by-case basis. While patients with autoimmune disorders are excluded from receiving immunotherapy—due to concerns of a bigger flare-up (see 

 has raised some hope for these patients, Madden said. The study, conducted in Australia, found that patients with advanced melanoma who had preexisting autoimmune disorders or those who had a major immune-related adverse event (irAE) with the early next-generation immunotherapy, ipilimumab, could potentially be treated with a programmed death ligand-1 (PD-1) inhibitor, with manageable immune toxicities. 

	Madden heard the presentation from that study’s senior author, Alexander M. Menzies, PhD, at the 2016 annual meeting of the American Society of Clinical Oncology. “Dr Menzies said that the results of their study could be applied to other cancers, as well, that are now treated with I-O drugs,” she told the audience at PCOC

. This study has raised hopes of cancer clinicians who can now expand the population of patients that receive treatment with PD-1 inhibitors. Madden believes that a cautious approach, which includes considering the individual patient characteristics and an open discussion with the patient, can make immune-based treatments available to those patients who did not qualify to participate in the clinical trial.

	Madden also drew attention to the fact that patients may have a variable response (time to response, type of clinical response, etc) to I-O, and some may experience a phenomenon described as “pseudo-progression.” Pseudo-progression is the initial period following treatment initiation when a tumor might actually grow in size before it shrinks. “These variations in response led to the creation of new immune-related Response Criteria for I-O agents—the criteria require confirmation of suspected disease progression about 4 weeks following treatment initiation, with subsequent radiographic testing,” she added.

	Madden then walked the audience through some of the most commonly observed adverse effects with immunotherapy, emphasizing the importance of a thorough explanation of these for the patients and family members. “It is critical for healthcare providers to urge their patients to monitor for any side effects during and in the months following immunotherapy, and to report all symptoms no matter how subtle they may seem,” Madden added.

		Menzies AM, Johnson DB, Ramanujam S, et al. Anti-PD-1 therapy in patients with advanced melanoma and preexisting autoimmune disorders or major toxicity with ipilimumab [published online September 29, 2016]. 

Immunotherapy treatments are not without side effects. What do patients and their families need to know so they are more aware?

Managing Patient Expectations With Immuno-Oncology

)™ are dedicating the February issue to immuno-oncology (I-O), and Cardinal Health has been a part of the conversation in each of the 3 issues. We marvel at the fact that it is a mere 5 years since the FDA approval of the first I-O of the modern era, the cytotoxic T-lymphocyte associated protein 4 (CTLA-4) inhibitor ipilumumab

; 2 years since the approval of the first 2 programmed death-1 (PD-1) inhibitors (nivolumab and pembrolizumab)

; and just months since the approval of the first programmed death-ligand 1 (PD-L1) antagonist (atezolizumab).

 In such a relatively short time, these I-O therapies have:

• Garnered FDA approvals in 6 tumor types

• Received indications for adjuvant, first-line metastatic, and salvage disease

• And, are likely to receive 5 additional tumor type approvals in the proceeding 12 to 18 months.

Key opinion leaders and subject matter experts openly conjecture the end of the chemotherapy era while the silence around precision medicine is deafening. More than half of all actively accruing cancer therapeutic trials involve I-O across 52 different malignancies as single agents, dual I-O regimens, and I-O in combination with chemotherapy and targeted therapy.

™ article concluded with the statement: “Stakeholder adoption of I-O is no longer a question of ‘IF’ but a question of ‘WHEN.‘ Who will be treated, with ‘what’ types of cancer, in ‘which’ stage and for ‘how’ long remain unanswered questions.”

 A year later, many of these questions are already being answered as new ones emerge, as I-O is poised to become the backbone of modern cancer treatment. Chief among these questions is ‘What lies beyond CTLA-4, PD-1, and PD-L1 in the future of I-O therapeutics?’ Most I-O treatments do not directly attack the tumor, rather, they mobilize the immune system to recognize and destroy the tumor. This can be achieved using various approaches, including antibodies, peptides, proteins, small molecules, adjuvants, cytokines, oncolytic viruses, bispecific molecules, and cellular therapies.

We believe the next I-O frontier to move from the bench to the bedside is cellular therapy in the form of chimeric antigen receptor (CAR)-T cells. In the first published trial from the University of Pennsylvania (U-Penn), 27 of 30 (90%) relapsed and refractory (R/R) patients with acute lymphoblastic leukemia (ALL) experienced complete remission 1 month after CAR-T infusion—22 (73%) of them had no evidence of minimal residual disease (MRD).

 Rapid, complete, and durable responses in highly refractory patients make CAR T a potential game-changer for cancer therapy, but the issues impacting stakeholder adoption for ex-vivo activated cellular I-O are significantly more complex than anything we’ve seen before.

History and Development of CAR-T Technology 

First and foremost in the discussion is recognizing that CAR T does not represent a drug, but, rather, a complex therapeutic process. Whereas most of the previously commercialized I-O interventions—from interferons to interleukins to checkpoint inhibitors&mdash;are essentially drug therapies, CAR T is operationally more similar to hematopoietic stem cell transplantation (HSCT). In fact, the concept of CAR T has its origin in the allogeneic bone marrow transplantation (BMT) of ALL. More than a quarter century ago, observations of durable remissions in patients with ALL, post BMT, who suffered graft versus host disease (GVHD) led to the understanding that donor or grafted T-cell recognition of malignant host lymphoblasts could impart long-term disease control (graft versus leukemia effect).

 The hypothesis generated was: if autologous T cells could be conditioned/manipulated to recognize malignant cells, then tumor control could be achieved without the negative consequences of GVHD.

When mild, GVHD is a complex chronic disease in which the grafted immune system is at war with the host organs; however, GVHD is life-threatening when severe. It would be critical to solve the problem of GVHD should any immune cellular therapy be successful. One method developed to create tumor recognition without the complications of GVHD involved reprogramming autologous T cells to identify and eliminate malignant cells through tumor-specific antigen recognition. The reprogramming required harvesting T cells from the patient via apheresis, transporting the cells to a wet lab where they could be chemically modified, and then altering the cells by linking the extracellular antigen recognition domain from a monoclonal antibody fragment to the T cell’s intracellular signaling domains.

 This newly modified autologous T-cell antigen receptor complex would then be a fusion, or chimera, of 2 proteins, or CAR. While still in the lab, the newly created CAR-T cells could then be incubated, or more technically, activated, to expand their number. Once adequately expanded, the CAR-T cells could be re-infused into the patient, but only after the patient is primed with chemotherapy to deplete their own circulating lymphocytes, which might dilute the CAR-T cells’ effectiveness. T cells engineered to express such CARs engage an antigen on a tumor cell through the extracellular antibody domain, thereby activating the T cells in a major histocompatibility complex—independent manner.8 Stated less scientifically, CAR-T cells can stimulate potent cytotoxic immune responses without the negative consequences of GVHD.

, we have summarized selective data from completed or ongoing phase I/II CAR-T trials, which have been published and presented. This early research has focused on cancers in which the malignant cells express CD19—an antigen expressed only on malignant and normal B cells. CAR-T cells expressing anti-CD19 recognize and kill CD19-expressing malignant cells.

Among the CD19-expressing malignancies, pediatric R/R ALL has garnered the most attention. CAR-T treatment of pediatric R/R ALL has resulted in remarkable clinical benefit and fewer severe adverse events (SAEs) than adult R/R ALL treated with CAR-T cells, making pediatric ALL the leading candidate for the first FDA-approved indication.

Stakeholder adoption will likely be brisk for the same reasons, but the overall healthcare impact might be limited given the nature of this disease and the relatively small number of eligible patients; 2500 to 3500 new pediatric ALL in the United States are diagnosed annually, 80% of which are of B-cell lineage (CD19-positive); current 5-year survival is 85%, and treatment-related mortality is 1% to 3%.

While responses are attained with blinatumomab in the small number of R/R patients, they are rarely durable and less than one-third of pediatric patients with R/R ALL are cured with allogeneic HSCT.

An update on immunotherapies and the potential impact of chimeric antigen receptor (CAR)-T cells on oncology care.

February 2017

Advanced APMs and the Emerging Role of Immuno-Oncology Agents: Balancing Innovation and Value

Helping Cancer Patients and Caregivers Navigate Immunotherapy Treatment

Q&A With Dr Jae Park on the Promise of CAR-T Cells in Cancer Care

From Bench to Community Oncology Clinic: The Promise of Immunotherapy

Managing Patient Expectations With Immuno-Oncology

CAR-T Cells: The Next Era in Immuno-Oncology

Keeping Pace With the Immunotherapy Revolution

Patient Navigation in Immuno-Oncology

AJMCtv® Interviews, February 2017

Medical World News, February 2017