, a member of my family underwent treatment for breast cancer. As she navigated the rigors of her treatment with a modified radical mastectomy and adjuvant chemotherapy (administered then without the effective antiemetic regimens of today), I recall the toll exacted upon her. Two decades later, as a fellow in bone marrow/hematopoietic cell transplantation, I recalled her experience as we attempted to push the boundaries of dose intensity in an attempt to more effectively care for patients with advanced, relapsed, and persisting malignancies. The side effects of these ever more intensive regimens proved challenging to many patients, and the experience showed us that increasing therapeutic intensity was ultimately limited in its potential effectiveness and applicability.

The quest for more effective cancer treatments has inspired generations of basic science researchers, medical oncologists, surgeons, and radiation oncologists to seek more effective and less morbid ways of treating patients. The extraordinary iterative efforts of basic scientists, physician investigators, and the pharmaceutical industry have led us to identify novel approaches outside the traditional triad of surgery/chemotherapy/radiation therapy for more effective treatment of patients with cancer. It is in this spirit of discovery and innovation that immuno-oncology has arisen as an essential avenue toward the more effective treatment of patients affected by a broad array of cancers.

Investigators, in the early 1970s, had identified immune mediators as a potentially important set of tools for treating patients with cancers. During this period, Time magazine heralded the availability of these “magic bullets” as potential game-changing medications for patients affected by chemotherapy-refractory tumors, such as melanoma and renal cell cancer. The actual effectiveness of interleukin-2 and lymphokine-activated killer cells never quite fulfilled the promise of the Time cover story, but they did showcase the potential importance of the immune system in cancer treatment.

Flash forward 40 years, and a Google search of the term “immuno-oncology” yields more than 531,000 hits. The glimmer of promise demonstrated by early trials of immunomodulating drugs in the 1970s presaged the current era in which immuno-oncologic agents have been licensed by the FDA at an astonishing rate. The pace of innovation and the increasing breadth of immuno-therapeutic agents over the past 3 decades has accelerated beyond what any of us thought might be possible—the armamentarium has grown to include agents from an astonishingly wide variety of drug classes. These “magic bullets” now include the original set of therapeutic monoclonal antibodies, monoclonal antibody/drug conjugates, bispecific molecules, oncolytic viruses, cancer vaccines, chimeric antigen-receptor (CAR) T-cells, and the growing numbers of checkpoint inhibitors.

It would be difficult to overstate the impact of these new agents in the treatment of a wide variety of cancers. Therapeutic monoclonal antibodies like rituximab and trastuzumab play an indispensable role in the initial treatment of patients with CD20—expressing non-Hodgkin lymphomas and her-2-neu–expressing breast cancers, respectively, resulting in significant improvements in overall survival (OS).

 Monoclonal antibody/drug conjugates, such as brentuximab, have demonstrated the ability to produce remissionsin previously refractory patients with Hodgkin lymphoma and improve OS for high-risk patients following transplantation. Emerging agents in this drug class have demonstrated significant promise in the treatment of patients with relapsed acute lymphoblastic leukemia (ALL) and acute myelogenous leukemia.

 The bispecific molecule blinatumomab has been approved for the treatment of patients with refractory and persistent ALL and can serve as an effective “bridge to transplant” for previously untreatable patients.

Beyond the emerging wealth of antibody-based therapeutics, immuno-oncologic innovation now includes treatments based upon the use of oncolytic viruses (T VEC hsv-1 for treatment of melanoma),

 cancer vaccines (Sipuleucel-T for treatment of prostate cancer),

 The increasing promise of these agents for treating patients with diagnoses that are typically refractory to standard chemotherapeutic approaches demonstrates the extraordinary promise of these novel therapeutics.

 published by a research group at the City of Hope, in Duarte, California, demonstrates the potential role for innovative immuno-oncological agents in the treatment of patients for whom therapeutic choices remain limited and largely unsatisfactory.10 In this case report, a patient with recurrent multifocal glioblastoma received intraventricular and tumor cavity—directed injections of CAR T-cells targeted at the interleukin-13 receptor alpha 2—more commonly known as IL13Rα2&mdash;as a tumor-associated antigen. The patient achieved a complete response and the response has persisted through the time of publication of the report, 7.5 months after the initiation of CAR T-cell therapy.

These agents are merely the beginning of an immuno-oncological revolution. The emergence of the checkpoint inhibitor class of agents with activity directed at programmed death-1 and programmed death-ligand 1, promise an even more robust armamentarium of immuno-oncological agents in the near term.

It is in this context that we are pleased to bring you this issue of 

™ in which the authors address many important aspects of this brave new field. Experts from the Cardinal Health Specialty Care Solutions provide an overview of CAR T-cell technologies and review how these therapeutics can be successfully integrated into patient care. Jae Park, MD, a CAR T-cell researcher and innovator from Memorial Sloan Kettering Cancer Center, provides his perspective on the value of these therapeutics in answering unmet patient needs. Shawn M. Regis, PhD, a patient navigator with the Lung Cancer Screening Program at Lahey Hospital & Medical Center, describes the various options offered by the hospital via its navigation program and addresses some unique aspects of navigation as it pertains to immuno-oncology. An article from authors at McKesson Specialty Solutions provides insight on how alternative payment models can absorb the impact of innovation in oncology care.

Over the past decade we have seen extraordinary advances in cancer therapeutics that have moved us far beyond what was imaginable early in my career. The idea of harnessing the power of the immune system as a means of bringing more effective, better tolerated treatment solutions to patients in need is deeply inspiring. As we have heard the heightened rhetoric associated with the Cancer Moonshot initiative, the increasing availability of immuno-oncological agents provides concrete evidence that understanding and conquering cancer is achievable. The more prosaic challenge is that of ensuring that as the wealth of new immuno-oncological agents come to market, they are used in an economically sustainable, effective, and patient-centered way.Joseph Alvarnas, MD, is director, medical Quality and Quality, Risk and Regulatory Management, City of Hope. He is also the editor-in-chief of 

		Lotze MT, Matory YL, Rayner AA, et al. Clinical effects and toxicity of interleukin-2 in patients with cancer. 

		Topalian SL, Rosenberg SA. Therapy of cancer using the adoptive transfer of activated killer cells and interleukin-2. 

		Coiffier B, Lepage E, Briere J, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large B-cell lymphoma. 

. 2002;346(4):235-242. doi: 10.1056/NEJMoa011795.

		Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. 

. 2001;344(11):783-792. doi: 10.1056/NEJM200103153441101.

		Kantarjian HM, DeAngelo DJ, Stelljes M, et al. Inotuzumab ozogamicin versus standard therapy for acute lymphoblastic leukemia. 

. 2016;375(8):740-753. doi: 10.1056/NEJMoa1509277.

		Topp MS, Kufer P, Gökbuget N, et al. Targeted therapy with the T-cell-engaging antibody blinatumomab of chemotherapy-refractory minimal residual disease in B-lineage acute lymphoblastic leukemia patients results in high response rate and prolonged leukemia-free survival. 

. 2011;29(18):2493-2498. doi: 10.1200/JCO.2010.32.7270.

		Grigg C, Blake Z, Gartrell R, Sacher A, Taback B, Saenger Y. Talimogene laherparepvec (T-Vec) for the treatment of melanoma and other cancers. 

. 2016;43(6):638-646. doi: 10.1053/j. seminoncol.2016.10.005.

		Small EJ, Schellhammer PF, Higano CS, et al. Placebo-controlled phase III trial of immunologic therapy with sipuleucel-T (APC8015) in patients with metastatic, asymptomatic hormone refractory prostate cancer. 

. 2006;24(19):3089-3094. doi: 10.1200/JCO.2005.04.5252.

		Hay KA, Turtle CJ. Chimeric antigen receptor (CAR) T cells: lessons learned from targeting of CD19 in B-cell malignancies [published online January 21, 2017]. 

		Brown CE, Alizadeh D, Starr R, et al. Regression of glioblastoma after chimeric antigen receptor T-cell therapy. 

. 2016;375(26):2561-2569. doi: 10.1056/NEJMoa1610497.

Articles

Evidence-Based Oncology

Keeping Pace With the Immunotherapy Revolution

 is often the scariest news a patient will hear in his or her lifetime. In addition to the physical toll of the disease itself, there are numerous other factors associated with a cancer diagnosis that can be far too burdensome for a patient to handle alone. For this reason, care coordination for all oncology patients is critical in providing the best possible outcome. With disease treatment being the main focus, communication among primary care physicians, oncologists, and other specialists involved in patient care becomes very important. Patient comorbidities and treatment side effects often need to be addressed as well. This could require involvement of a range of subspecialty providers, including those in pulmonology, cardiology, dermatology, nutrition, and physical and occupational therapy (

	Beyond these physical concerns, there is a large psychosocial burden associated with a cancer diagnosis. We know that psychosocial issues affect oncology patients regardless of stage and that the patient’s emotional response to the diagnosis has an impact on both morbidity and mortality.

 While many patients do eventually adjust effectively to their new circumstances without requiring intervention, more than one-third will experience significant distress requiring clinical support

; although many patients depend on family, friends, and religious leaders for support, others also need intervention in the form of a social worker or psychologist.

	Beyond the clinical needs, there are also financial and logistical considerations when coordinating cancer care. Fighting cancer can be an expensive battle, and assistance from a financial counselor (either personal or assigned by the hospital) can prove beneficial. Patients also need to coordinate transportation to and from their (often multiple) appointments to receive care while deciphering the logistics to take time away from work if necessary. All of these factors combined make managing a cancer diagnosis a daunting task for any patient, and assistance from a navigator can help ease the burden (

). This is true for all oncology patients, but there are some unique challenges pertaining to the rapidly developing field of immuno-oncology (I-O).

	The field of I-O has grown rapidly over the past 5 years, enough to now be considered the “fourth pillar” of oncology treatment,

 along with surgery, radiation, and chemotherapy. One of the side effects of being a relatively new modality is that knowledge of the field is somewhat limited among patients and even some providers. A needs assessment conducted by the Association of Community Cancer Centers, in 2014, showed that only 7% of community clinicians reported being “extremely familiar” with emerging I-O therapies, while 39% responded that they were either “not at all familiar” or only “slightly familiar” with these therapies.

 Thus, the very first piece of the puzzle in care coordination is to ensure providers are familiar with these treatments so they can discuss them with patients when appropriate. The patient must also be well informed to be effectively engaged in a shared decision-making process. However, with increasing demands on physicians’ time, they may not be able to devote as much time as preferred on patient education. Therefore, a patient navigator who is knowledgeable of the field can be a great asset in answering patient questions and marshaling available resources as needed.

	Often times, when patients think about the side effects of cancer treatment they jump to horror stories they have heard about the hair loss, nausea, and vomiting, historically attributed to cytotoxic chemotherapy. While it is true that I-O drugs do not have these same side effects, significant toxicities can still occur. Because the goal of I-O drugs is to ramp up the immune response against cancer, it can also trigger unwanted autoimmune or inflammatory responses.

 Common side effects associated with I-O are diarrhea, rash, and fatigue; additionally, I-O agents have been known to cause toxicity in the liver, thyroid, lung, and colon. Making patients aware of these adverse events should be a part of patient education, and patients should also have access to resources to help manage these side effects—access to dermatologists or gastrointestinal specialists who are familiar with the field of I-O. Coordinating appointments with these specialists, in addition to the regular treatments, is an important patient navigator function. 

	An argument could be made that a patient navigator can have the most impact in the care coordination of I-O patients by helping them navigate financial assistance. By 2020, the cost of cancer care in the United States is expected to reach $157 billion.

 This high cost could, in part, be attributed to I-O therapies, as the average cost for a course of this treatment in the United States is $120,000 to $150,000 per patient and could go higher if combination therapies are indicated.6 Of note, some predict the market size for I-O agents alone will be over $30 billion by 2022, equal to the cost of all anticancer drugs in the United States for 2016.

 With specialty tiers of insurance typically requiring patients to pay somewhere in the range of 20% to 25% of medication costs,

 patient co-pays could range anywhere from $35,000 to $40,000. This can often lead patients to either refuse I-O therapy due to the high cost, or choose between treatment and other necessities in their lives. Adding in the fact that many patients can’t work while undergoing treatment, and therefore may lose insurance, the problem becomes even more complex. 

	Data suggest that patients with cancer are roughly 2.5 times more likely to go bankrupt than those without cancer and that the severe financial distress caused by out-of-pocket expenses related to cancer treatment is associated with a 79% increased risk of death.

 With such high stakes, the costs for which the patient may be held responsible should be part of the shared decision-making process regarding cancer treatment, although often that is not the case. The conventional decision flow when it comes to cancer treatment selection is drug effectiveness, followed by drug toxicity, and finally cost.

 It is important for patients to be made aware of the expense they can expect to incur as a result of receiving I-O for cancer treatment, and what options are available for financial assistance. A patient navigator can play a huge role in this area.

	There are many options available to assist patients with the expenses associated with their oncology care. In addition to standard health insurance, these can include government programs, co-pay relief and patient assistance programs, assistance from volunteer organizations, and fundraising. However, it is not enough to simply notify a patient about these options; they also need guidance on whether they are eligible for this funding, and need to be informed of how to apply and obtain it. Patient navigators can connect with these different networks and help identify options that will generate the most benefit for the patient, and assist with the application process. 

	Because the cost of I-O therapies is high, and insurance companies often struggle to stay abreast and provide coverage for these rapidly emerging treatments,

 many pharmaceutical companies offer assistance programs that can help patients with the cost of treatments, both beyond what their insurance will cover as well as for potential off-label use that most insurers will not cover. To apply, patients typically need to supply personal financial documents, including the previous year’s tax returns, and/or a financial hardship statement attesting that even if they could “afford” the treatment, the burden of co-pays and other cost sharing would create a financial hardship. It is also important to note that while enrolling in such programs can lead to getting the treatment drug for free, the costs of the actual infusion (such as charges for supplies and intravenous catheter insertion) are still not covered. Navigators who are well educated in the field of I-O can be enormously beneficial when it comes to finding assistance programs like these.

Navigation Doesn’t End When Treatment Does

	As with all oncology care, the primary objective of coordinating care for patients receiving I-O therapy is to provide assistance throughout the care continuum. This includes survivorship, palliative, and hospice care, as applicable after treatment. Patients will continue to have follow-up visits, imaging, lab work, etc, and continue to require assistance in coordinating the care and costs. The benefits of survivorship programs have been well established, and there are often many questions and challenges associated with the transition to palliative and hospice care. Patient navigation should exist over this entire spectrum for oncology patients. Additionally, there are specific challenges associated with the rapidly evolving field of I-O that make having a patient navigator with extensive knowledge of the field a very valuable resource.&ensp;

Shawn M. Regis, PhD, is a patient navigator, Lung Cancer Screening Program, Lahey Hospital & Medical Center. 

		Gorman LM, Boyle DA. The psychosocial impact of cancer on the individual, family, and society. In: Psychosocial Nursing Care Along the Cancer Continuum. 2nd ed. Pittsburgh, PA: Oncology Nursing Society; 2010:1-23.

		Hutchison SD, Steginga SK, Dunn J. The tiered model of psychosocial intervention in cancer: a community based approach. 

. 2006;15(6):541-546. doi: 10.1002/pon.973.

		Advancing immuno-oncology in the community setting. Institute for Clinical Immuno-Oncology website. http://accc-iclio.org/wp-content/uploads/2016/01/ICLIO-White-Paper-Final.pdf. Accessed December 12, 2016.

		Seiden MV. Immuno-oncology 2016 and beyond: the opportunities, challenges, and risks. 

		Cancer prevalence and cost of care projections. National Cancer Institute website. http://costprojections.cancer.gov/. Accessed December 12, 2016.

		Marks A, Chapman MA. Improving patient access to immuno-oncology therapies. The Physician’s Perspective: A Health Policy Brief from the Institute for Patient Access. Institute for Patient Access website. http://1yh21u3cjptv3xjder1dco9mx5s.wpengine.netdna-cdn.com/wp-content/uploads/2015/10/Improving-Patient-Access-to-Immuno-Oncology-Therapies_Oct-20151.pdf. Published October 2015. Accessed December 12, 2016.

		Bankruptcy may portend greater mortality risk in patients with cancer. ASCO Annual Meeting website. https://am.asco.org/bankruptcy-may-portend-greater-mortality-risk-patients-cancer. Published May 31, 2015. Accessed December 12, 2016.

		Cost of cancer drugs should be part of treatment decisions. ASCO Annual Meeting website. https://am.asco.org/cost-cancer-drugs-should-be-part-treatment-decisions. Published May 31, 2015. Accessed December 12, 2016.

Patient navigation is immensely helpful in relieving some of the burden placed on cancer patients, and there are some particularly unique aspects of navigation as it pertains to immuno-oncology.

Patient Navigation in 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.

Analogous to ALL, other CD19-expressing hematologic malignancies have been targeted with CAR-T cells. While the CAR-T cells used in these studies target anti-CD19, they are not all identical. The methodology to develop the fusion protein that makes a CAR T is unique to each manufacturer and represents 1 variable that may be responsible for differing efficacy and toxicity outcomes. The U-Penn group reported an overall response rate (ORR) of 57% (complete response [CR], 29%) in a cohort of patients with R/R chronic lymphocytic leukemia (CLL).

The National Cancer Institute (NCI) reported on 15 patients: 9 with R/R diffuse large B-cell lymphoma (DLBCL), 2 with R/R indolent lymphoma, and 4 with R/R CLL.14 Of the entire NCI cohort of 15 patients, 8 achieved CRs; 4, partial remissions (PRs); and 1, stable disease. Investigators at the Fred Hutchinson Cancer Research Center (FHCRC) reported on 34 R/R non-Hodgkin lymphoma (NHL) patients, 18 of whom had DLBCL; 6, follicular lymphoma (FL); 6, CLL; and 4, mantle cell lymphoma (MCL).

CRs in studied subtypes were: 38% in DLBCL, 67% in FL, and 50% in CLL.

Another study by the U-Penn group included 38 R/R patients who had either FL (14), DLBCL (21), or MCL (3).

The median number of prior therapies was 4 (range: 1-10) and 32% of patients had prior autologous HSCT. ORR among 22 evaluable patients at 3 months was 54% in DLBCL, 100% in FL, and 50% in MCL. The 3-month ORR was 54% in DLBCL, 100% in FL, and 50% in MCL.

The ZUMA-1 study confirmed multi-center CAR-T treatment feasibility, with the following reported results on 51 relapsed/refractory DLBCL patients treated with KTE019; Orr was 76% with CR in 47%.

Finally, preliminary data also support activity in myeloma where studies are ongoing to explore how this strategy is best positioned among other recently approved novel antimyeloma agents.

A critical component of the CAR-T treatment is the preinfusion conditioning regimen to reduce the circulating and competing T-cell population. Conditioning regimens varied in published studies suggesting that the conditioning program could be another factor impacting differential efficacy and toxicity. It is becoming increasingly clear that the selection of the conditioning program will be essential to optimize clinical outcomes, especially SAEs. Some patients in the trials presented were treated with fludarabine plus cyclophosphamide conditioning, while others received cyclophosphamide monotherapy. In one study, the combination regimen resulted in a higher CR (42% versus 8%), positioning it as a benchmark, if not a standard, in this nascent field of research.

The rapidity with which CAR-T treatment has become the standard of care in pediatric R/R ALL, as well as expanded indications across R/R B-cell CD19—expressing malignancies—such as CLL, DLBCL, MCL, and others&mdash;may have more to do with managing SAEs than with efficacy. The SAE that has garnered the most attention is cytokine release syndrome (CRS) because it is the most dangerous toxicity, usually occurring shortly after infusion although it can be delayed up to 3 weeks after.

Cytokines are immune cell signaling proteins that we associate with flu-like symptoms, which, if released into the circulation rapidly and in large amounts (cytokine storm), can be physiologically overwhelming and lead to vascular collapse and possible death.

Grading of CRS toxicity has not been uniformly agreed upon. Severe CRS occurred in 7/16 (44%) patients in the Memorial Sloan Kettering Cancer Center (MSKCC) trial, 8/30 (27%) at U-Penn, 6/21 (29%) at the NCI, and 7/30 (23%) at FHCRC.

Deaths attributed to CRS have been suggested in only 2 out of 97 pediatric patients with R/R ALL (2%). The Juno Rocket trial has been held twice by the FDA due to SAE-related deaths, albeit not necessarily CRS-related. Observations that CRS may be mediated by IL-6 led to tocilizumab (Genentech anti—IL-6) and etanercept (anti–TNF) use.26 IL-6 rescue appears to be an intriguing strategy to manage CRS, but its standardization and overall impact on treatment remains to be determined as patients who do not have CRS are unlikely to respond. The strongest predicting factor to developing severe CRS is the leukemia burden.

Guidelines are being developed to manage CRS—most require that C-reactive protein (CRP) be monitored daily to identify patients becoming at risk, while tocilizumab and/or steroids are recommended for high-risk patients.

Fevers, hypotension, and a variety of neurological symptoms (confusion, obtundation, myoclonus, and aphasia) have been frequently reported, as have fatigue, diaphoresis, anorexia, and diarrhea. Neurotoxicity deserves special mention, as it is a potentially lethal toxicity and appears unrelated to CRS. Neurotoxicity, its prevention, and its relationship to tumor response are not well understood. Tumor response is clearly the basis for tumor lysis syndrome, which can occur even 3 weeks following infusion; it was noted as late as day 22 in a CLL patient in the first published CAR-T report.10 The research into predictability, prevention, and management of SAEs without abrogating the clinical benefit of CAR-T therapy will be a critical element to the success of this I-O intervention.

Although the salvage therapy of B-cell malignancies may become the earliest FDA-approved indications for CAR-T therapy, long term commercial success will require broader disease indications and labeling for use at earlier stages of disease. Methodologically, chimeric fusion protein design against antigens other than CD19, is not a limitation, nor do such antigens need to be associated with blood cells. A review of the active and accruing clinical trials provides insight into this possibility. Of the 57,889 oncology trials listed on ClinicalTrials.gov, 777 matched for checkpoint inhibitors and 121 matched for CAR T. Of these 121 CAR-T trials, 58 are being conducted in China. Of the remaining 63 trials conducted in the United States and/or the European Union, 39 are phase 1, 14 are phase 1/2 hybrid, and 5 trials are phase 2; the phase is not identified for the remaining 5 (

). The phase 2 trials all focus on hematologic malignancies expressing CD19. Of the 40 trials with a projected completion date before 2019, the CAR-T platform is being tested in melanoma, sarcoma, ovarian cancer, and brain tumors based on targetable antigens other than CD19. Of particular note are 6 trials involving brain malignancy, specifically glioblastoma multiforme, a disease with limited therapeutic progress over the preceding 30 years and for which CAR-T success could lead to a fast-track FDA approval and a frontline indication.

The complexities of CAR-T synthesis and delivery make clinical benefit just one aspect of commercial viability. FDA approval of CAR-T treatment is just the first barrier to overcome in their incorporation into routine cancer therapeutics. Manufacturers need to prepare to scale these products and develop wrap-around services to ensure that their unique characteristics are not a barrier to adoption. Some of these characteristics include site of care, fragility of the patient, apheresis, cryogenic transport, and cost of the therapy. Today, CAR-T treatment is only available in clinical trials through a limited network of specialized centers. This limited network will likely be maintained upon approval since the manufacturers and FDA will want to ensure that the administering center is accredited in a similar fashion to the Foundation for the Accreditation of Cellular Therapy (FACT).

Travel and boarding for very sick patients and their caregivers should be an important consideration, along with referral to these sites from regional hematologists and oncologists. Educational platforms on the referral process, side effects, and relapse management are needed for all stakeholders. The delay between apheresis and the infusion of the CAR-T therapy also represents a possible barrier. Manufacturing cannot begin until the successful completion of an apheresis process, which some patients may not tolerate, while for others the manufacturing time may be clinically impractical. Allogeneic CAR-T alternatives that avoid the logistical complexities of apheresis and patient-specific manufacturing are under active investigation but appear years behind in clinical development. Finally, only a handful of vendors offer cryogenic transport.

Despite numerous uncertainties that can impact the commercial potential of CAR-T therapy, it is noteworthy that the leading compounds are supported by well-capitalized and committed companies. A conservative industry assessment of the commercial potential of this novel therapy puts the total market for CAR-T therapy in excess of $1.5 billion by 2020. Based on projected study completions and FDA filings, the first approved indication will likely be pediatric and young adult R/R ALL, followed by R/R DLBCL. Market models also expect commercially viable approvals for R/R MCL and R/R CLL, although some of these likely depend on the postapproval success of the initial indications.

The actual cost of therapy remains to be determined, but patient-specific manufacturing is costly and not easily scalable. In determining the cost, it is important to note that all steps in the CAR-T process require a Good Manufacturing Practice (GMP) facility or similar accredited environment. The highly trained physicians and nurses, the specialized facilities for manufacturing and administration, and the ongoing research and development will dictate that the cost of this therapy will be well north of 6 figures and likely benchmarked against allogeneic HSCT with which it will compete in many indications. The additional cost of transportation and boarding during the side-effect period and care between apheresis and infusion would challenge traditional payment and reimbursement models. Once CAR-T treatment is FDA-approved and used commercially, reimbursement strategies for institutions and physicians will be among the most significant questions to impact adoption. One possibility is a bundled payment approach, wherein a limited number of institutions will be allowed to administer therapy with payments based on predefined contractual agreements that include outpatient apheresis, inpatient hospitalization, and post discharge toxicity monitoring. There is precedent for such an approach as this is standard practice for HSCT reimbursement.

Preliminary results from the Novartis Eliana global study, conducted in 25 centers across 8 countries, which were presented at the American Society of Hematology annual meeting in December 2016, illustrate the complexity, excitement and caution surrounding CAR T. The trial enrolled 87 pediatric and young adult patients with CD19-positive R/R B-ALL (average age, 12 years; range, 3-23 years). There were 5 manufacturing failures, 6 patients died before undergoing infusion, and 3 patients discontinued therapy before infusion because of AEs. A total of 62 patients underwent infusion. Efficacy data on the first 50 patients revealed that 41 patients (82%) achieved CR and were found to be negative for MRD at 3 months. AEs of grade 3 or 4, suspected to be product-related, were seen in 74% of patients in the first 8 weeks and in 10% of patients after 8 weeks. CRS was observed in 79% of patients (grade 3 in 27% and grade 4 in 27%), with average onset on day 3 (range, 1 to 22 days) and an average duration of 8 days (range, 1 to 36 days). More than half (59%) of the 49 patients who developed CRS were admitted to the intensive care unit, 20% underwent invasive ventilation, and 10% underwent dialysis. No treatment-related deaths were observed.

CAR-T treatment, specifically Novartis CTL-019, will likely get FDA approval for R/R ALL in the pediatric population. Label restrictions requiring failing blinotumumab are unlikely, as this treatment is not “curative” and both treatments may be a bridge to an allogeneic HSCT—a known curative treatment.

Label restrictions might also include site-of-care restrictions, (eg, FACT-accredited networks). Such site-of-care restrictions are unlikely to be a barrier in the pediatric ALL population as these patients are currently treated in academic institutions, most already FACT-accredited for HSCT; however, the majority of eligible adult patients with hematologic malignancies and solid tumors would require referrals to such centers, often from the community. Logistical, operational, and financial aspects of such referrals become significant in managing a population of fragile patients with advanced malignancy and the significant CAR-T production variables.

As with any new drug or medical device, there are a myriad, and mundane, issues related to launch. CAR-T treatment, being a complex process, complicates this considerably because the apheresis center, CAR-T manufacturing, preparatory chemotherapy for lymphocyte depletion, intensive care management post CAR-T reinfusion, and postprocedure surveillance all need to be considered in logistics and pricing. We suspect that akin to HSCT, payment bundling will be the method of choice; patients, providers, and treatment centers will need education and coordination in reimbursement from payers. Monitoring patients after completion of therapy for possible late complications will likely be part of a mandatory phase 4 research program required by the FDA given the likely fast-track status of first indications. Manufacturers might need help in disseminating information regarding “centers of excellence for CAR-T” to community oncologists so that eligible patients are identified and referred.

Although a number of the factors described will contribute to the commercial success of these compounds, including final label, pricing, and clinical data, the largest driver of market uptake may be timing to first approval and initial experience with a commercial product. Once approved, CAR-T therapy will likely continue the trend of I-O therapeutic success. On the heels of CTLA-4, PD-1, and PD-L1, activated cellular therapy in the form of CAR-T cells will further the transformation of systemic cancer care from a chemotherapy to an I-O platform. However, the expansion of I-O platforms across an increasing number of malignancies, their indication in earlier lines of treatment, the anticipated use of I-O in combination, and trial designs that treat until progression may quickly erode the enthusiasm over their clinical benefit as stakeholders become mired in the debate over their cost.&ensp;

Bruce A. Feinberg, DO, is vice president and chief medical officer, Cardinal Health Specialty Solutions, Cardinal Health.

Jennifer Fillman, MBA, is vice president and general manager, Specialty Services, Cardinal Health Specialy Solutions, Cardinal Health.

Justin Simoncini, MBA, MPH, is vice president for strategy, Cardinal Health Specialty Solutions, Cardinal Health.

Chadi Nabhan, MD, MBA, FACP, is vice president and chief medical officer, Cardinal Health Specialty Solutions, Cardinal Health.

E-mail: bruce.feinberg@cardinalhealth.com

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

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

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.  

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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

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.

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?

February 2017

Keeping Pace With the Immunotherapy Revolution

Patient Navigation in Immuno-Oncology

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

From Bench to Community Oncology Clinic: The Promise of Immunotherapy

Managing Patient Expectations With Immuno-Oncology

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

Medical World News, February 2017

AJMCtv® Interviews, February 2017