	For makers of cancer therapies, the regulatory environment in Europe is likely to become more like that of the United States, and the FDA may extend its reach to areas such as next generation sequencing.

	That’s what an industry expert told attendees gathered at a joint symposium of the American Society of Hematology (ASH) and the European Hematology Association, during the 56th Annual Meeting of ASH held at the Moscone Center in San Francisco.

	David R. Parkinson, MD, of New Enterprise Associates, Inc, in Menlo Park, California, offered an industry perspective on the current regulatory climate, while Ann T. Farrell, MD, spoke on behalf of the FDA. Both Farrell and Parkinson spent time discussing the growing challenges in the molecular diagnostics realm, an area where the FDA seeks increased oversight to ensure reliability.

the diagnostics industry has been rocked by uncertainty over reimbursement, which has resulted in lawsuits and the loss of some small companies. Plus, the FDA moved on July 31, 2014, to extend oversight to an estimated 11,000 laboratory developed tests, including highly complex tests to direct cancer treatment and other chronic illnesses.

	While this move was seen by some as essential to ensure patient safety, it is viewed by others as overregulation that will stifle creativity in genomic medicine. Others in the industry are taking a pragmatic view: if regulation must come, perhaps the FDA’s blessing will also mean the path to payer reimbursement will become clear. Dueling viewpoints were featured in the January 5, 2015, issue of 

, apublication of the Journal of the American Medical Association.

went to press, the FDA was holding a 2-day workshop, “Framework for Regulatory Oversight for Laboratory Developed Tests.”

	During the ASH session, Parkinson explained that payers began demanding evidence of clinical utility relatively recently, from an industry with “no tradition” of providing such studies. Most observers date the shift to around 2011, and say it emerged suddenly and snowballed, to the shock of the industry. Regulation of diagnostics industry, meanwhile, lacks the maturity seen on the therapeutic side, Parkinson said. And yet the need to match the right drugs to the right patients—and the increased focus on smaller groups of patients and therapeutic targets&mdash;makes molecular diagnostic testing increasingly important, which demands more regulatory stability and policy solutions, he said.

	Fifteen years ago, if one had suggested widespread investment by pharmaceutical companies in orphan disease, “You would have been laughed out of the room,” Parkinson said. But over time, the combination of incentives created by 1983 legislation and poor returns on other investments by the drugmakers have caused the industry to look to smaller groups of patients for whom the return on investment may not be huge, but at least more certain. Collaborations with academia and more unique financial arrangements with philanthropy to manage risk have changed the playing field.

	“If the field is to move forward, there needs to be investment,” he said. Without it, “treatment will not advance.”

	Before Parkinson spoke, Farrell discussed the factors that go into FDA decision making: essentially, regulators balance known benefits against known risks. The EMA has “exceptional circumstance,” and the FDA now has an “accelerated approval” process for therapies to treat life-threatening illnesses that are superior to available treatments. The FDA’s increased flexibility in the cancer area, in particular, has been praised. Post-marketing studies are typically needed. When it comes to orphan diseases, Farrell said the FDA aims for regular approval because the agency realizes how difficult it is to do a clinical trial in the first place.

	Despite the increased flexibility, the drug approval process in the United States is viewed worldwide as the most expensive and highly uncertain. Parkinson concluded the session with a call for Congress to act to give regulators and CMS new tools, or drug costs will continue to increase.

	“All regulatory agencies are data driven,” Farrell said. The data provided by drug makers must inform product labeling to ensure safety and efficacy “whether it’s a drug, a biologic, or a device.”

	With an accelerated approval, the FDA wants to see evidence in the published literature, which can be based on a surrogate endpoint. The FDA will also likely ask to see additional studies after approval is granted.

	The agency defines clinical benefit not only as improvement in survival, Farrell said, but in “how a patient feels, and how a patient functions.”

	In the diagnostic area, Farrell said there are 4 issues where the FDA envisions oversight in the development of companion diagnostic devices:

	• the identification of patients who are likely to benefit from a therapy

	• the identification of patients who are likely to be adversely affected by therapy

	• monitoring responses to treatment with therapy

	Some companion diagnostics were developed in tandem with therapies, but Farrell said that is not always possible, and FDA developed protocols that recognized it does not always make sense to withhold therapy just because the diagnostic is not yet available.

	When ponatinib appeared for chronic myeloid leukemia, for example, the FDA looked at prior approvals for imatinib, nilotinib, and dasatinib for guidance, Farrell said. “We decided to approve it without reference to the test,” she said, but, “We took our post marketing tests very seriously.” 

	1. Caffrey MK. When science outpaces the payers: reimbursement in molecular diagnostics. 

	2. Caffrey MK. Studies see value of prostate cancer diagnostic test, but will CMS pay for it? 

	3. Caffrey MK. FDA moves to regulate thousands of regulatory tests. 

	4. Sharfstein J. FDA regulation of laboratory-developed diagnostic tests: protect the public, advance the science [published online January 5, 2015]. 

	5. Evans JP, Watson MS. Genetic testing and FDA regulation: overregulation threatens the emergence of genomic medicine [published online January 5, 2015]. 

	6. Public workshop: framework for regulatory oversight of laboratory developed tests (LDTs), January 8-9, 2015. FDA website. http://www .fda.gov/MedicalDevices/NewsEvents/WorkshopsConferences/ucm423537.htm. Accessed January 8, 2015.

Articles

Evidence-Based Oncology

Bigger Regulatory Challenges in Diagnostics Than in Therapeutics, Industry Expert Says

	Results presented December 8, 2014, at the 56th Annual Meeting of the American Society of Hematology (ASH) show that 88% of patients with relapsed or refractory mantle cell lymphoma (MCL) responded to a combination of ibrutinib and rixtuxmab.

	The phase 2 trail, led by Michael Wang, MD, of the University of Texas MD Anderson Cancer Center in Houston, found responses in 40 of 46 patients, with a complete response (CR) in 40%.

 The trial also revealed an apparent marker for who will benefit most from the combination. Results found that in 34 evaluable patients with levels of less than 50% of the Ki-67 protein, the overall response rate (ORR) was 100%. Conversely, 10 patients who discontinued treatment when their MCL progressed had Ki-67 levels above 60%.

	Ibrutinib, being developed as Imbruvica by Pharmacyclics and Janssen Biotech,Inc, may offer an option in combination for patients whose MCL is especially difficult to treat, Wang said.

Previously, Wang and colleagues reported a 68% ORR in patients with relapsed/ refractory MCL when ibrutinib was used as a monotherapy.

	“The positive outcomes seen with Imbruvica in combination with rituximab reinforce our decision to pursue its full potential as a single agent and in combination with other therapies, and underscores the potential Imbruvica may offer to patients living with hematologic malignancies,” said Danelle James, MD, MS, vice president, clinical development, Pharmacyclics

ibrutinib for more than 2 years remained 

progression-free with no new or unexpected 

to results presented December 8, 2014, at 

ASH.4 This second phase 2 trial looked at 

ibrutinib’s safety and efficacy as a monotherapy 

original study, 47% were still alive at the 

	More than 30% of patients with relapsed 

once-daily ibrutinib in 120 patients with 

	Wang also presented a poster with results 

found that the ORR, which was the primary 

follow-up of 14.9 months, and 21% of the 

of response (DOR), progression-free survival 

(PFS), overall survival (OS), and safety. 

	The most frequently reported AEs of any grade were fatigue (43%) and diarrhea (43%). Diarrhea, when observed generally occurred early after initial treatment, but resolved quickly and was not treatment limiting. The majority of AEs were grade 1 and 2. The most common AEs ≥ grade 3 were neutropenia (21%), thrombocytopenia (13%), and pneumonia (13%). Atrial fibrillation was reported in 13 patients (11%); 6 patients (5%) experienced Grade 3 or 4 atrial fibrillation which resolved in 1 to 4 days. Five of these 6 patients had a history of atrial fibrillation.

	1. Wang M, Hagemeister F, Westin JR, et al. Ibrutinib and rituximab are an efficacious and safe combination in relapsed mantle cell lymphoma: prelimary results from a phase 2 clinical trial. 

	2. Imbruvica (ibrutinib) in combination with rituximab data shows positive benefit-risk profile in hematologic malignancy [press release]. San Francisco, CA: Pharmacyclics; December 8, 2014.

	3. Wang M, Rule S, Martin P, et al. Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma. 

	4. Imbruvica (ibrutinib) data demonstrates safety and durability of responses at 2-year follow-up in mantle cell lymphoma [press release]. San Francisco, CA: Pharmcyclics; December 8, 2014.

	5. Wang M, Goy A, Martin P, et al. Efficacy and safety of single-agent ibrutinib in patients with mantle cell lymphoma who progressed after bortezomib therapy. Blood. 2014;124(21):abstract 4471.

Data Show High Response Rate to Ibrutinib Combination for Patients With Hard-to-Treat MCL

	Research on platelets, on lenalidomide in myelodysplastic syndrome (MDS) and sorafenib in acute myeloid leukemia (AML), highlighted the plenary session held December 7, 2014, at the 56th Annual Meeting of the American Society of Hematology (ASH) in San Francisco. Presentations at the session were selected by the Program Committee from among the thousands of scientific abstracts that were accepted for the meeting.

	Renata Grozovsky, PhD, a research fellow at Brigham and Women’s Hospital, Boston, delineated an in vitro and in vivo mechanism, regulated by the JAK2-STAT3 signaling pathway, which regulates platelet production. Thrombopoietin (TPO) was discovered in 1958 but only identified as a ligand of the c-MPL receptor in 1994. While TPO is a well-studied regulator of platelet production, supporting the survival, proliferation, and differentiation of platelet precursors, and bone marrow megakaryocytes, mechanisms regulating circulating TPO levels have been a topic of debate, Grozovsky said. Through a collaboration with scientists across Brigham and the Department of Biotechnology, University of Rijeka, Croatia, Grozovsky provided evidence that platelets lacking sialic acid (desialylated platelets) are removed by the hepatic Ashwell-Morell receptor (AMR), thereby regulating platelet survival and hepatic TPO levels.

	“We hypothesized that clearance of desialylated platelets by AMR increases TPO in the liver,” said Grozovsky. Her research team found that preventing the expression of the asialoglycoprotein receptor (Asgr2) subunit of AMR in mice improved platelet survival compared to the control mice. In fact, Asgr2

 mice had lower liver TPO mRNA levels, as well as expressed platelets that were desialylated. Mice lacking the sialyltransferaseST3GalIV, on the other hand, had an increase in liver TPO mRNA. Desialylated platelets isolated from St3gal4

 mice infused into WT mice increased hepatic TPO mRNA levels, plasma TPO levels, and bone marrow megakaryocytes. However, desialylated platelets infused into Asgr2

 mice had no effect on TPO mRNA synthesis, TPO plasma levels, or bone marrow megakaryocyte numbers, researchers found.

	To identify the underlying signaling mechanism, Grozovsky described conducting biochemical evaluation of the mouse liver cells and human HepG2 cells: within a half hour of ingesting desialylated platelets, increased phosphorylation of the tyrosine kinase JAK2 was observed in St3gal4

 mice and a marked reduction in JAK2 phosphorylation in Asgr2

 mice. “When we treated the cells with the JAK1/2-specific inhibitor, AZD1480, we observed reduced STAT3 phosphorylation and nuclear translocation, and reduced expression of both the TPO mRNA and protein in HepG2 cells incubated with desialylated platelets.” The results were translated in vivo in mice; treating the control wildtype mice with AZD1480 blocked TPO mRNA induction by the desialylated platelets. Grozovsky concluded that clearance of aging desialylated platelets by AMR has a substantial clinical significance, considering that the JAK1/2 inhibitor often causes thrombocytopenia.

	All the presentations during the plenary session were delivered by senior research investigators, with the exception of the talk by Emma Fink, an MDPhD student in the laboratory of Benjamin L. Ebert, MD, PhD, Brigham and Women’s Hospital, Boston. Her talk was titled “Lenalidomide induced ubiquitination and degradation of CSNK1A1 in MDS with del(5q).”

	Lenalidomide is a highly effective treatment for multiple myeloma and MDS with deletion of chromosome 5q (del(5q)). Recent work from their laboratory and others demonstrated that lenalidomide activates the CRBN-CRL4 E3 ubiquitin ligase to ubiquitinate IKZF1 and IKZF3. Degradation of these lymphoid transcription factors explains lenalidomide’s growth inhibition of multiple myeloma cells and increased IL-2 release from T cells. “We hypothesized that ubiquitination of a distinct CRBN substrate in myeloid cells could explain the efficacy of lenalidomide in del(5q) MDS,” Fink stated.

	She went on to describe quantitative proteomic experiments in the myeloid KG-1 cells, which identified casein kinase 1A1 (CSNK1A1), a novel target that had increased ubiquitination and decreased protein abundance following lenalidomide treatment. Csnk1a1, being encoded in the del(5q) commonly deleted region, is a potential lenalidomide target in del(5q) MDS.

	“We validated that lenalidomide treatment decreased CSNK1A1 protein levels in multiple human cell lines in a dose-dependent manner without altering Csnk1a1 mRNA levels,” said Fink.Moreover, lenalidomide treatment increased ubiquitination of CSNK1A1 in cell lines. Previous work from Ebert’s laboratory had shown that CSNK1A1 was a negative regulator of p53 and β-catenin. So their research group worked on the hypothesis that lenalidomide would induce degradation of CSNK1A1, resulting in the specific apoptosis of haploinsufficient del(5q) cells.

	To tease out the mechanism, they conducted co-immunoprecipitation experiments, which pulled down CSNK1A1 with CRBN in the presence of lenalidomide, demonstrating a direct interaction of CSNK1A1 with the substrate adaptor for the ubiquitin ligase. Mixing CRBNCRL4 with CSNK1A1 demonstrated in vitro ubiquitination of CSK1A1. These results were further validated in a genetically defined CSNK1A1 conditional knockout mouse model. While murine cells were found resistant to the effects of IMiDs, murine Ba/F3 cells overexpressing human CRBN (hCRBN), but not murine CRBN, degraded CSNK1A1 in response to lenalidomide. “This could explain why thalidomide, which was found responsible for acute teratogenicity in humans, failed to show any toxicity in mouse experiments,” Fink explained. Finally, her group observed that CSK1A1 expression was sensitive to lenalidomide in del(5q) MDS patients. Fink concluded her talk by stating that lenalidomide provides the first example of an FDA-approved and clinically effective drug that derives its therapeutic window from specifically targeting a haploinsufficient gene.

	The final presentation during the plenary session provided results from a multi-collaborative trial, the SORAML Trial (NCT00893373), conducted in Germany, presented by Christoph Röllig, MD, from Universitätsklinikum in Dresden, Germany. The trial was designed to evaluate the kinase inhibitor sorafenib as add-on to standard chemotherapy-as-backbone induction and consolidation treatment in patients with acute myeloid leukemia (AML). The primary eligibility criteria for the trial, which enrolled 276 patients from 25 centers over a period of 2.5 years, were newly diagnosed AML, aged 18 to 60 years, and suitability for intensive therapy. “Our exclusion criteria included heart disease, anaplastic leukemia, hypertension, surgery, or open wounds,” said Röllig. Röllig presented the following treatment plan:

	Two cycles of induction with daunorubicin (DA) (DA 60 mg/m

: days 3 to 5, with cytarabine 100 mg/m2 as a continuous infusion: days 1 to 7), followed by 3 cycles of high-dose cytarabine consolidation (3 g/m2 once a day on days 1, 3, and 5). Nonresponders received a second induction with high-dose cytarabine and mitoxantrone (HAM) (cytarabine 3 g/m

 once a day on days 1 to 3, plus mitoxantrone 10 mg/m

: days 3 to 5). Allogeneic stem cell transplantation was scheduled for all intermediate-risk patients in first complete remission with a sibling donor and for all high-risk patients with a matched related or unrelated donor. At study inclusion, patients were randomized to receive either sorafenib (800 mg/day) or placebo as add-on to standard treatment in a double-blinded fashion. Study medication was administered on days 10 to 19 of DA I+II or HAM, from day 8 of each consolidation until 3 days before the start of the next consolidation, and as maintenance for 12 months after the end of consolidation.

	The patients were nearly evenly split between the study arm and the placebo arm, and the median cumulative dose of study medication was similar between the arms. At the end of the trial, analysis of the results found no difference in the complete remission (CR) rates between the sorafenib arm and the placebo-controlled arm, showed Röllig: CR was 59% with placebo and 60% with sorafenib (P = .764). However, he presented a significant difference in event-free survival (EFS) rates between the 2 arms: 22% versus 40% EFS for placebo and sorafenib, respectively. He pointed out that the relapse-free survival (RFS) rate was 38% in patients treated with placebo following standard treatment, while patients treated with sorafenib had a RFS of 56%. Patients in the sorafenib arm were at an increased risk for fever, infections, and bleeding events.

	Röllig concluded that in younger AML patients, the addition of sorafenib to standard chemotherapy in a sequential manner is feasible and associated with antileukemic efficacy. He emphasized, however, that confirmatory trials will be necessary to establish sorafenib as a new standard therapy for AML. 

Best of ASH Presentations: Platelets, Lenalidomide for MDS, and Sorafenib in AML

development of better drug delivery systems, 

down treatment costs are just a few of the strategies that can contribute to improved patient care, especially from a drug developer’s perspective. However, innovation can prove challenging for the pharmaceutical industry, especially with respect to reimbursement.

fall of 2014. Participants included Irwin 

W. Tischler, DO, national medical director, 

	Revolutionizing patient care, however, needs much more, as was revealed during conversations with payer representatives from leading managed care enterprises during the Oncology Stakeholders Summit: Insights discussion organized by 

MD, physician lead—cancer, Humana. Peter Salgo, MD, professor of medicine and anesthesiolog at Columbia University and associate director of surgical intensive care at NewYork-Presbyterian Hospital, interviewed the experts.

	Salgo began by asking the experts what were the most influential innovations in oncology over the previous decade. Tishcler considered personalized treatment and molecular diagnostics to individualize treatment as most important; he regarded these developments as a means to reduce side effects and provide care tailored to treat a specific genetic abnormality, and only sees the role of personalized therapy evolving and getting even more specific over time. Loy recognized the increasing openness among various groups about their cancer experiences. He thinks we have come a long way, with all stakeholders involved—patients, payers, providers, and policy experts&mdash;grabbing on to a common platform to discuss cost-effective ways of utilizing technology to improve patient care. “We wouldn’t have heard that 10 to 12 years ago,” he said.

	Loy acknowledged that molecular testing has had a huge impact on cancer treatment options. He sees even more opportunity in gathering stakeholders to make best of this tremendous scientific achievement. Citing Kentucky, his home state, as an example, Loy said that contextualizing risk is difficult for some patients. With the biomarker tests, however, results and disease risk can be assigned a definitive value to help bring things into perspective for the patient. The dialogue also highlights shared accountability among all involved.

	Rep Fred Upton (R-Michigan) and Rep Diana DeGette (D-Colorado) have launched the 21st Century Cures initiative to “bridge the gap between the science of cures and the way the therapies are regulated.” A dialogue has already begun between the committee and various stakeholders from the healthcare world.

 “Do you see this initiative impacting some of the regulatory barriers that currently impact the industry?” asked Salgo. Tischler said he expects this initiative, coupled with the influence of the current digital revolution, to improve patient access to novel therapies. He said the initiative is looking for suggestions and solutions to move the process without the oversight and regulation that have been a barrier to drug development thus far. Loy, too, acknowledged that the initiative is a healthy first step to hasten the drug development process so patients gain access to novel treatment options. Whether and how they exploit available treatments will vary, he said.

	Both Loy and Tischler agreed that the pharmaceutical industry faces tremendous risks during product development, but Tischler believes the initiative is working to overcome some of these barriers. “If we can adopt something along these lines that this bill is purporting to do, it may lower some of the costs and enable us to use some of the technologies that are available. And I think that if there is still a return on their investment dollar and their research dollars, they won’t be as adverse to it,” he said. Loy also believes in the potential of an adaptive clinical trial design, especially in the search for breakthrough therapies. According to Loy, the existence of guidelines alone would bring tremendous clarity to the drug development process, even if it does not have a direct influence on the pace of innovation.

PERSONALIZED MEDICINE AND THE CHALLENGE OF PHARMACOGENOMICS

	While personalized medicine presents a tremendous opportunity to improve treatment outcomes, the challenge lies in its high cost, analyzing the vast amount of data generated from the genomic tools, and making sense out of those tools. Tischler stated that pharmacogenomics applications are in preliminary stages and currently do not have any clinical utility, but that payers end up covering their expenses anyway. Loy agreed, saying that payers need to be convinced about the value of spending money on personalized treatment options while distinguishing between the clinical utility of a genomic test versus patient eligibility for a future trial.

	An important consideration that needs improvement is the lack of communication between all those involved in personalized testing, said Loy. This results in tests being conducted but results not being shared to allow for more-informed treatment decisions. This is especially important when decisions to not treat a patient are made based on a test. “You really need to make sure that if you are deciding not to treat, that you’re not living with regret later on because of your unknown risk tolerance and unknown understanding of probability,” Loy said.

MEDICARE REIMBURSEMENT POLICIES AND PHARMACEUTICAL INNOVATION

	Both Loy and Tischler pointed to several issues associated with Medicare, especially sequestration, which primarily harmed reimbursement rates for oncologists. And patients who stand to gain from the treatment have high cost sharing or high deductibles, which, in cancer care, has resulted in bankruptcies, said Loy. To help ease difficult decisions of choosing between treatment and affording a normal life, Loy’s solution is to hold multistakeholder conversations now, rather than later, and to center them around cost issues. He thinks these decisions must

	be made early on in the treatment process to help patients “fight their battle by making reasonable choices, rather than wait until a catastrophic situation arises.”

	One of the solutions that Tischler suggested was having 1 deductible and 1 co-payment that would cover the entire treatment, rather than individual co-pays per visit or per prescription. “We’re talking about it with some employer groups, with our national teams to see if by one deductible, one co-pay, it covers their entire treatment,” he said. 

Improved Cancer Care Through Innovation

	With the growing burden of the cost of cancer therapy, for both payers and society as a whole, cost-effectiveness discussions are on the rise among all stakeholders—payers, providers, and patients. Organizations like the American Society of Clinical Oncology have joined the discussion and are developing a framework that could help physicians and patients reach treatment decisions together. While the healthcare system in the United States is struggling to balance access to care with the cost of that care, comparative effectiveness research (CER) could lead to better-informed healthcare decisions.

	The value of CER was discussed by a group of payer representatives during the Peer Exchange convened by 

 in September 2014, Oncology Stakeholder Summit: Evidence-Based Decisions to Improve Quality and Regulate Costs. Participants included John L. Fox, MD, MHA, senior medical director and associate vice president of Medical Affairs at Priority Health; Ira M. Klein, MD, MBA, FACP, national medical director, Clinical Thought Leadership, Office of the Chief Medical Officer, Aetna Inc; Michael Kolodziej, MD, national medical director for Oncology Strategies, Aetna Inc; Bryan Loy, MD, physician lead—Cancer, Humana; and Irwin W. Tischler, DO, national medical director, Oncology, Cigna. The session was moderated by Peter Salgo, MD, professor of medicine and anesthesiology at Columbia University and associate director of surgical intensive care at NewYork- Presbyterian Hospital.

	Kolodziej began the discussion with a comparison between the European healthcare system and that of the United States. While CER guides policy decisions in Europe, especially by Britain’s National Institute for Health and Clinical Excellence (NICE), it has not found widespread acceptance in the United States, with critics equating CER with rationing of healthcare to save costs. The Patient-Centered Outcomes Research Institute (PCORI), a product of the Affordable Care Act, was considered by many as a solution to tackling CER, but was prevented from considering the cost of care in its research, Kolodziej said. “So I think that this is a fertile soil. I don’t think the payers are going to do it, but I think they’re dying to use it,” he added.

	He went on to cite a project that he is involved in, a project to identify the optimal drug sequence in breast cancer and renal cell cancer. Although this is a very challenging task, Kolodziej said that pointing out the worst sequence would be equally effective. Loy added that while CER has been used by pharmacies and pharmacy benefit managers for some time (as step therapy), it could have tremendous utility in the healthcare delivery model.

	When Salgo asked the payers about CER in a clinical trial setting, several of them agreed that it would be a huge advantage to trials. CER works as the phase 4 of a clinical trial for the FDA, said Klein, “a post trial real-world analysis” that would provide a much clearer picture of a drug’s performance than an actual clinical trial with its highly controlled environment would.

	When the discussion moved toward the importance of including quality-adjusted lifeyears (QALYs) in CER, Kolodziej emphasized the role of patient-reported outcomes in the QALY discussion. The real question, the panel agreed, is whether decisions should be made on a case-percase basis after evaluating a patient’s status and respecting patient opinion, or whether a general policy should be crafted after establishing cost-effectiveness of a therapy. As the discussion circled back to patient age and cost of care, Tischler suggested that in the case of

	an older patient, the treating physician should be obligated to discuss the cost of therapy with the patient and the family. “Like I used to say to my patients, I could add a lot of years to your life or some years to your life, but I’m not going to add a whole lot of life to your years, and what price are you willing to pay for that? I think that’s where the discussion should go,” he added. While these extremely important discussions on cost of care are in their preliminary stages, Tischler said he could foresee them being a part of mainstream healthcare decisions in the near future.

	Fox concurred, and emphasized the importance of communicating available options to the patients and family members, stating that the question of “rationing” care may not arise if the patient is well aware of the different ways to achieve the desired outcome. “In our experience in working with providers to do advanced care planning around patients who have terminal diseases, a lot of patients, once they fully understand the options, say, ‘You know, I don’t want more treatment. I want to be kept comfortable,’” added Fox.

	While CMS is prohibited from considering CER to approve coverage for a particular treatment, Fox said that payers have a straightforward method of accounting for a very expensive drug: increased premium or co-pay. Klein added that these increases in patient cost-sharing lead to an informal rationing, with a steep decrease in adherence. “We’re creating a multi-tiered system in which rationing occurs by the financial burdens we put on people, and we put those burdens on people actuarially because we have decided not to fix the problem on the front end,” said Klein. 

Payers Look to CER for Improved Healthcare Decisions

	Payers in the United States would see a reduction in overall medical costs if patients switched to newer, novel oral anticoagulants, based on a study of 10 clinical trials involving dabigatran, rivaroxaban, and apixaban.

	Results of the study were presented December 6, 2014, at a poster session on health services and outcomes research during the 56th Annual Meeting of the American Society of Hematology (ASH), which took place at the Moscone Center in San Francisco, California.

	The study’s lead author, Alpesh N. Amin, MD, MBA, consults for Bristol- Myers Squibb (BMS) and for Pfizer, joint makers of apixaban. The authors sought to review recent clinical trials for new oral anticoagulants and compare event rates for patients taking these newer therapies for nonvalvular atrial fibrillation (NVAF) and venous thromboembolism (VTE) with those taking standard therapy or placebo.

	In this study, the authors started with treatment costs at the 2013 level and adjusted for inflation, with costs projected from 2014 through 2018. Projections were based on a hypothetical health plan of 1 million members, and prevalence of both conditions was derived from published literature. The authors assumed the same usage rate for all 3 newer therapies when making comparisons.

	For 2014, a hypothetical health plan of 1 million insured lives would see medical savings of $3 million by using dabigatran, $2.1 million by using rivaroxaban, and $7.3 million by using apixaban for its NVAF patients.

	For acute VTE, savings were $700,000 for dabigatran, $2.2 million for rivaroxaban, and $4.1 million for apixaban. Savings for the VTE patients for extended periods would be $6.3 million for dabigatran, $6.6 million for rivaroxaban, and for apixaban, $9.5 million for the 2.5-mg arm and $9.6 million for the 5-mg arm.

	In 2014, savings for the combined NVAF and VTE populations are projected to be $10 million with dabigatran, $10.9 million with rivaroxaban, and $21 million with apixaban. Savings from 2015 through 2018 were projected to steadily rise for all 3 therapies, although the greatest savings relative to standard care would come in the earliest years of treatment. The authors recommend confirming the results in real-world settings.

. Two presentations at the December 6, 2014, poster session concerned sickle cell disease (SCD), which received considerable attention at the 56th ASH Annual Meeting. The first examined patient and caregiver perspectives on adherence to iron chelation therapy (ICT), which is used to manage iron overload in patients with SCD and other anemias who have repeat transfusions. Interviews with 11 patients and 10 caregivers from 6 cities in the United States were coded through a consensus process. Children were not interviewed if they were younger than 9 years.

children got older. Several coping mechanisms were reported, such as efforts to mask the taste. The lead author and all but 1 coauthor are employed by Novartis.

	Respondents said reasons for adherence included perceived positive effects of ICT on health and longevity, support from caregivers and clinicians, and an established routine for taking treatment. Reasons for nonadherence included not liking the taste, or aftertaste, or texture of the therapy or its side effects, such as gastrointestinal symptoms. Mealtime restrictions were also an issue. Caregivers said children who had a better understanding of the benefits of treatment had better adherence and that adherence improved as 

	A study based at the University of Wisconsin examined the impact of blood transfusion therapy on the quality of life on children with SCD. A group of 196 children in the Multicenter Silent Infarct Transfusion Trial were divided into 2 groups: those who received at least 18 months or more of transfusion (effectively transfused) and those who received less than 18 months. Parents or guardians completed assessments using the Child Health Questionnaire at baseline, at study exit, or at a neurological event. The group was 43% female with a mean age of 9.55 years, and 92% were African American. The groups were equal by gender, disease severity, and rates of pain. At study exit, results showed that children in the effectively transfused group had higher scores in the following areas:

	• physical function (M = 12.68; SE = 3.52), t (174) = 3.61, P ≤.001;

	• bodily pain (M = 13.16, SE = 3.74), t (174) = 3.51, P ≤.001;

	• change in health (M = 0.39; SE = 0.14), t (166) = 2.71, P =.01.3

	The authors described these results as the first evidence that blood transfusion improves health-related quality of life for children with SCD. Mast Therapeutics provided research funding for the study. 

	1. Amin, AN, Bruno A, Trocio J, Lin J, Lingohr-Smith M. Comparison of medical costs avoided when new oral anticoagulants are used for the treatment of patients with atrial fibrillation and venous thromboembolism in the US. 

	2. Bal V, Cote I, Lasch K, Huang V. Patient and caregivers perspectives of factors associated with adherence to and satisfaction with iron chelation therapy. 

	3. Beverung LM, Strouse JJ, Hulbert ML, et al. Health-related quality of life in children with sickle cell disease: impact of blood transfusion therapy. 

Results Project Savings for Payers With Novel Oral Anticoagulants

	Results from a large phase 3 prospective randomized open-label trial comparing imatinib 400 mg daily with dasatinib 100 mg daily were presented by Stephen O’Brien, MD, professor of hematology, Newcastle University Medical School, Newcastle upon Tyne, England. He presented the results of SPIRIT 2, which compared the 2 drugs in patients with newly diagnosed chronic myelogenous leukemia, at the 56th Annual Meeting of the American Society of Hematology, held in San Francisco.

	According to O’Brien, the SPIRIT 2 trial design was similar to the DASISION trial. The trial recruited 814 patients at 172 hospitals across England and in Northern Ireland between August 2008 and March 2013. The primary end point of the trial was event-free survival at 5 years. Key secondary end points listed in the trial were the rate of achievement of a major molecular response (defined as BCR-ABL/ABL ratio of less than 0.1%), cytogenetic response, and toxicity. The trial had an even distribution of patients between the 2 arms.

(5 deaths while on treatment). Following discontinuation, an additional 11 patients from the imatinib arm and 15 from the dasatinib arm died. The research group is currently following 124 of the patients in the imatinib arm and 89 in the dasatinib arm.

	With a median follow-up of 37.4 months, O’Brien said 300 patients have discontinued the study medication: 170 in the imatinib arm (7 deaths while on treatment) and 130 in the dasatinib arm 

	While there were no unexpected side effects observed, O’Brien said that patients receiving imatinib experienced GI toxicity more often than patients receiving dasatinib; fatigue, rash, and headache were more common with dasatinib. Also, a higher rate of grade 3/4 thrombocytopenia was observed in the dasatinib arm, pleural effusions occurred in 78 of 406 (19.2%) patients on dasatinib, and 13 of 78 (16.7%) patients required drainage. No significant differences in cardiovascular adverse events were observed, he noted.

	While significant differences in major cytogenetic response and complete cytogenetic response were observed, with dasatinib presenting a better effect, O’Brien cautioned that a large amount of data was missing in this analysis. This could, in reality, render the difference insignificant.

	O’Brien concluded that dasatinib-treated patients have a higher rate of molecular response at 1 year, but, with a median follow-up of 37.4 months, there is no significant difference in rates of disease progression or overall survival. He suggested the need for additional follow-up to evaluate differences in event-free survival at 5 years, if any. 

SPIRIT 2: Dasatinib Superior to Imatinib in Newly Diagnosed CML

	Several research groups gathered at the 56th Annual Meeting of the American Society of Hematology in San Francisco discussed findings from trials conducted in patients suffering from chronic myelogenous leukemia (CML) to prevent disease progression to advanced stages. Their session, held December 7, 2014, was called “Chronic Myeloid Leukemia: Outcomes With TKI therapy.”

CA180-056),” he reported the results of the final 5-year analysis of DASISION. As has been published earlier, patients with newly diagnosed CML-CP were randomized to receive dasatinib 100 mg once daily (n = 259) or imatinib 400 mg once daily (n = 260). The primary end point was confirmed complete cytogenetic response (cCCyR) by 12 months. Long-term efficacy and safety data from patients with the predefined minimum 5 years of study treatment were presented.

	Jorge E. Cortes, MD, deputy department chair, Department of Leukemia, Division of Cancer Medicine, the University of Texas MD Anderson Canc Center, Houston, presented results from the DASISION trial. In his talk, “Final Study Results of the Phase 3 Dasatinib Versus Imatinib in Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase (CML-CP) Trial (DASISION, 

	Cortes reported that 61% of dasatinib-treated patients and 63% of imatinib-treated patients were still on their initial study therapy at the end of the period. Cytogenetic and molecular response rates continued to be higher for dasatinib compared with imatinib (intent-to-treat population). The rate of cCCyR by 5 years was particularly higher with dasatinib when compared with imatinib (83% vs 78%, P =.187), as were the rates of major molecular response (MMR; BCR-ABL ≤0.1%; 76% vs 64%; P=.002) and MR4.5 (BCR-ABL ≤0.0032% IS; 42% vs 33%; P = .025) by 5 years.

arm. Fewer CML-CP patients in the dasatinib cohort (4.6%) progressed to the accelerated phase (AP) and blast phase (BP) compared with imatinib (7.3%). However, 5-year progression-free survival (PFS) and overall survival (OS) rates were similar across treatment arms. Significantly greater number of patients on dasatinib achieved BCR-ABL ≤10% at 3 months (84%) compared with those on imatinib (64%). And among the patients who achieved BCRâ€‘ABL ≤10% versus >10% at 3 months, improved PFS, OS, and lower rates of transformation to AP/BP were maintained at 5 years for both drugs.

	Further, he showed data that confirmed the times to cCCyR (95% CI; HR = 1.46, P =.0001) and MMR (95% CI; HR = 1.54; P <.0001) in all randomized patients were faster with the dasatinib 

“While adverse events for both arms were as we expected, the total incidence of pleural effusion continued to increase each year in dasatinib-treated patients,” he said. Discontinuation of 

dasatinib due to pleural effusion occurred in only 15 patients. Arterial ischemic events were uncommon. However, cardiovascular (CV) ischemic events and transient ischemic attack were reported in 10 and 2 dasatinib-treated patients, respectively, while CV ischemic and peripheral arterial occlusive events were reported in 4 and 2 imatinib-treated patients, respectively.

	According to Cortes, although the number of mutations following 4 to 5 years of treatment increased slightly in dasatinib-treated patients, the spectrum of mutations remained the same. 

	Cortes concluded that at the end of 5 years, 100 mg of dasatinib once daily presented superior outcomes compared with 400 mg of imatinib once daily as initial therapy for CML. He based his conclusion on the faster time to cCCyR and MMR, with more patients achieving BCR-ABL ≤10% at 3 months, sustained higher cumulative rates of response, and a lower rate of disease progression. According to Cortes, “Dasatinib offers meaningful advantages for patients with newly diagnosed CML-CP and remains a standard of care in this setting.”

	Susanne Saussele, MD, University of Heidelberg, Mannheim, Germany, was also a participant in this session. She discussed therapy goals for MMR in CML, based on the CML-Study IV. “We sought to evaluate a failure time point for MMR using data of the CML-Study IV, a randomized 5-arm trial designed to optimize imatinib therapy, alone or in combination. We also evaluated the optimal time point to achieve an MMR,” said Saussele.

	In the current European LeukemiaNet (ELN) recommendations, the optimal time point to achieve MMR is defined at 12 months after diagnosis of CML.

 “Not achieving MMR is not recommended as failure by ELN,” said Saussele. “So there are uncertainties about when CML therapy can be altered in patients not reaching MMR after 12 months.”

remission levels (MR4 or deeper), monthly landmarks were defined between 1 and 5 years after diagnosis. A patient was considered to be in MR2, MMR, or MR4 from the first diagnosis of 

the corresponding remission level and could only change to a higher level of response. Patients were censored after a stem cell transplant. For the failure time point analysis, for each of the resulting 48 landmarks, a Cox model was used to define the time to progression with age and EUTOS score as additional prognostic factors.

	In the study, patients with valid molecular analysis on MR4 level were randomly divided into a learning sample (LS) and a validation sample (VS). For the LS, MR2, MMR, and deep molecular 

	Between 2002 and 2012, 1551 patients were randomized to LS or VS and 1358 had a valid molecular analysis on the MR4 level. Of the 1228 evaluable patients, two-thirds were randomly allocated to the LS (n = 818) and one-third to the VS (n = 410). Percentage of patients in the LS with MR2, MMR, and MR4 or deeper at 1 year were 28%, 29%, and 14%, respectively, and at 5 years were 5%, 21%, and 71%, respectively. Forty-four patients of the LS reached MMR on second-generation tyrosine kinase inhibitors. Saussele identified a significant PFS advantage for patients in MMR (P =.018). Eight years following treatment, the probability of PFS for patients in MMR was 90.8% compared with 80.5% of patients not in MMR.

	Saussele said that the results of their model show that an optimal time point to predict PFS in patients with MMR was defined at 2.25 years after diagnosis, which could be construed as being significant. Further, at any time point, patients in MMR had a lower risk of progression than patients not in MMR. “This model can help determine when MMR is a failure and when a change in therapy should be considered. However, we should be aware that the earlier MMR is achieved, the higher is the chance to achieve deep molecular response later during therapy,” concluded Saussele. 

	1. Baccarani M, Deininger MW, Rosti G, et al. European LeukemiaNet recommendations for the management of chronic myeloid leukemia:2013. 

CML Updates: Defining MMR and Results of the DASISION Trial

	Results from a pair of phase 2 studies involving pomalidomide were reported December 8, 2014, during oral abstract sessions on treatments for multiple myeloma, as researchers continue to develop new combinations for patients who have stopped responding to earlier treatments.

	Pomalidomide, an immunomodulatory drug marketed as Pomalyst, received FDA approval in February 2013 for multiple myeloma patients whose disease is demonstrating progression despite having had at least 2 other therapies, including lenalidomide and bortezomib.

	Results presented featured 2 combinations. A phase 1/2 study found pomalidomide with bortezomib and dexamethasone to be highly effective, with confirmed responses over 80%.

 A second study determined that pomalidomide with cyclophosphamide and dexamethasone was superior to pomalidomide and dexamethasone only.

Pomalidomide, bortezomib, and dexamethasone.

	Martha Q. Lacy, MD, of the Mayo Clinic, presented results involving 50 patients who had previously been treated with 1 to 4 therapies (median 3) and were not responding to lenalidomide.

The median age of the patients was 66 years; 51% were female. The median time from diagnosis to the time of the study was 46 months, and 68% had received a stem cell transplant.

	Dosing was as follows: in phase 1, 9 patients started on 4 mg of pomalidomide on days 1 to 21, bortezomib 1 mg/m

 weekly, and 40 mg of dexamethasone weekly. For 6 patients, dosing of bortezomib was increased to 1.3 mg/m

, and this dose level was adopted for the larger group of patients in phase 2.

	At 9 months, 72% of the patients were progression free, 96% were alive, and 66% continued treatment. Common adverse events (AEs) were anemia, fatigue, leukopenia, and thrombocytopenia, with the majority grade 1/2. AEs grade 3 and higher and their total occurrences were neutropenia (29) leukopenia (15), lung infection (6), lymphopenia (8), dyspnea (3), and syncope (3). Pulmonary embolism occurred in 1 patient. Among the 42 patients who could be evaluated, confirmed responses were seen in 34, including 9 of 11 highrisk patients. Median progression-free survival (PFS) was 17.7 months.

TREATMENT WITH AND WITHOUT CYCLOPHOSPHAMIDE

	Previously reported results of pomalidomide with dexamethasone had an overall response rate (ORR) of 33% and median PFS of 4.2 months in patients who had previously been treated with bortezomib and lenalidomide. This phase 2 trial involving 70 randomly assigned patients compared 1 arm of patients receiving the pomalidomide-dexamethasone combination (median age, 63 years) with a second arm also receiving cyclophosphamide (median age, 64 years).

	Dosing of dexamethasone was adjusted by age, and patients not receiving cyclophosphamide were allowed to cross over to join that arm if their disease progressed. After a median follow up of 15 months, ORR (partial response or better) for the arm receiving pomalidomide and dexamethasone was 39%, while it was 65% for the arm also receiving cyclophosphamide. Clinical benefit (minimal response or better) was 64% for pomalidomide plus dexamethasone and 79% for the combo plus cyclophosphasmide. Median PFS was 4.4 months compared with 9.2 months for the 2 arms, respectively. Grade 3/4 AEs were more frequent in patients receiving cyclophosphamide, although the authors reported that these were not statistically significant.

12 who did. During the study, 13 patients crossed into the second arm. 

	While the study ended in March 2014, the authors reported that as of July 2014, 28 of the original 70 patients had died—16 who did not start out in the arm receiving cyclophosphamide and 

	1. Shilane J. Pomalyst: questions and answers about the FDA approval. The Myeloma Beacon. http://www.myelomabeacon.com/news/2013/02/13/pomalyst-pomalidomidequestions-and-answers-fda-approval/. Published February 13, 2013. Accessed December 9, 2014.

	2. Lacy MQ, LaPlant BR, Laumann KM, et al. Pomalidomide, bortezomib, and dexamethasone (PVD) for patients with relapsed lenalidomide refractory multiple myeloma (MM). 

	3. Baz R, Martin TG, Alsina M, et al. Pomalidomide, cyclophosphamide, and dexamethasone is superior to pomalidomide and dexamethasone in relapsed and refractory myeloma: results of a multicenter phase 2 study. 

Sessions Report Phase 2 Results of Pomalidomide Combinations

	In March 2014, Dana Farber Cancer Institute’s Kenneth C. Anderson, MD, raised expectations at the annual gathering of the National Comprehensive Cancer Network when he said it wouldn’t be long before patients and clinicians in multiple myeloma (MM) practice would have “a monoclonal antibody or 2,” the new class of therapy that trains the patient’s immune cells to attack the cancer.

	Based on the results presented at the 56th Annual Meeting of the American Society of Hematology (ASH) in San Francisco, Anderson’s prediction is right on schedule. On December 8, 2014, Anderson’s colleague at Dana Farber, Paul G. Richardson, MD, presented final results from a phase 1b/2 study of elotuzumab in combination with lenalidomide and dexamethasone for relapsed/refractory MM patients, including 73 who had already been treated with an average of 2 other therapies.

	Results show highly encouraging overall response rate (ORR) and progression-free survival (PFS), with the responses even better at the lower dose of 10 mg/kg of elotuzumab than the higher dose of 20 mg/kg. However, during the question-and-answer period Richardson warned, “We have to be careful how we interpret that.”

	Elotuzumab, given by intravenous infusion, is being developed by Bristol-Myers Squibb in collaboration with AbbVie. The therapy binds to signaling lymphocytic activation molecule F7 (SLAMF7), giving it a different mechanism of action from other monoclonal antibodies under study, daratumumab and SAR650984, which target the CD38 protein. These therapies were stars at ASH 2014, with studies spotlighted in a press conference and a major lecture at the conference. The FDA granted breakthrough therapy status to the combination of elotuzumab with lenalidomide and dexamethasone in May 2014, based on promising phase 1 results. Daratumumab gained breakthrough status in May 2013 as a single agent.

	The phase 2 study included patients who had 1 to 3 prior therapies, including those with at least 1 prior therapy from the phase 1 study; their median age was 63 years. Half the patients received 10 mg/kg of elotuzumab, while the other half received 20 mg/kg of the drug, and treatment was in 28-day cycles. Patients also received oral lenalidomide at 25 mg for days 1 through 21 and oral dexamethasone (28 mg, plus 8 mg on days when the elotuzumab was given). This pretreatment was designed to manage infusion reactions. Notably, ORR were 92% among patients in the 10-mg/kg group who responded to treatment compared with 76% for those in the 20-mg/kg group.Median PFS was 32 months for the 10-mg/ kg group and 25 months for the 20-mg/kg group.

	A stringent complete response or complete response was observed in 14% of patients, with a very good partial response seen in 43%; another 27% had a partial response. Richardson said researchers were struck by both the quality and durability of these responses. “It’s important to see, because many patients were on therapy for a number of years,” he noted. Common adverse events were diarrhea (66%), which Richardson described as manageable; fatigue (56%); muscle spasms (62%); constipation (51%); nausea (48%); and upper respiratory tract infections (47%). 

	1. Richardson PG, Jagannath S, Moreau P, et al. Final results for the 1703 Phase 1b/2 study of elotuzumab in combination with lenalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma. Blood. 2014;124 (21): abstract 302.

	2. Elotuzumab receives breakthrough therapy designation for multiple myeloma. http://www.myelomabeacon.com/news/2014/05/19/elotuzumab-breakthrough-therapy-designation-multiple-

	myeloma/. Published May 21, 2014. Accessed December 17, 2014.

Promising Results for Elotuzumab Presented in Session on Multiple Myeloma

revealing how to identify who should be treated early. Promising results are expected on monoclonal antibodies, said Jesus F. San Miguel, MD, PhD, of the Clinica Universidad de Navarra

	Those who treat patients with multiple myeloma have witnessed a sea change in the past 15 years. Yet another revolution appears right around the corner, with research on risk stratification 

	On December 6, 2014, San Miguel delivered the Han-Wasserman Lecture, “Multiple Myeloma: A Modern Model for Scientific and Clinical Progress,” at the 56th Annual Meeting of the American Society of Hematology (ASH), which convened at the Moscone Center in San Francisco, California.

	During his lecture, San Miguel previewed results that came later in the meeting on daratumumab, which targets CD38. Daratumumab, which received FDA breakthrough status in May 2013, and elotuzumab, which gained the status in 2014, have been highly anticipated by multiple myeloma patients and the clinicians who treat them. One of San Miguel’s slides said results showed improved survival of 30% to 35% for daratumumab as a single agent, and 64% to 75% of patients in combination with lenalidomide and dexamethasone.

	San Miguel said it has become clear that the disease “should not be considered a single entity, but different entities,” and thus, multiple treatment options will exist. For example, he said, many thought there would be no role for melphalan after the 2013 ASH meeting in New Orleans, which saw the paradigm-shifting results from Thierry Facon, MD, on lenalidomide and low dose dexamethasone. But San Miguel said that despite those results, melphalan remains a viable treatment option.

	The talk opened with an overview of the increased understanding of the genetics behind myeloma, which is building awareness that treatments must be tailored to the individual. Identifying and measuring key “drivers” of the disease holds great promise, San Miguel said, as this will give clinicians the information to create combination therapies for more patients. While survival has increased from the abysmal rates of 1 to 3 years of years past to 5 to 7 years today, more can be done, he said.

	San Miguel spent considerable time on an area where his group, the Spanish Myeloma Group, made a major contribution in 2013: risk-stratification of those precancerous patients who show signs of “smoldering” myeloma, and identifying for early treatment those at highest risk of developing the disease.

	He was the senior investigator of the phase 3 trial published in the 

 in which patients were randomized to be treated with lenalidomide and dexamethasone or observation, the latter being the usual standard of care for patients who have an increase of plasma cells in the bone marrow that produce the monoclonal immunoglobulin, but do not have any symptoms. San Miguel outlined the prognostic factors that allowed the research team to segment out the high-risk group. “You want to give the patient what is needed, and nothing more than is needed,” he said.

especially his wife for many sacrifices. A final slide was a photo of a popular Spanish football team, with faces of his colleagues replacing those of the star players. He thanked the patients, and their families, and the pharmaceutical leaders who have contributed to the revolution in treating multiple myeloma. “This is why we become doctors; this is the reason why we are hematologists,” he concluded. 

	These results produced improved 3-year survival rates among the high-risk patients identified and treated by the Spanish team: 94% of the treated group was still alive at 5 years, compared with 78% in the untreated group.

While most of his talk involved cutting-edge science, San Miguel ended on a highly personal note. He thanked his research team in Spain, his family, and 

	1. Spanish Myeloma Group study a treatment milestone. CenterWatch Newsline. http://www.centerwatch.com/newsâ€online/article/5124/spanishâ€myelomaâ€groupstudyâ€ aâ€treatment milestone#sthash.bo7URvWm.dpbs. Published August 5, 2013. Accessed December 5, 2014.

Early Treatment, Monoclonal Antibodies Discussed in Multiple Myeloma

	Hematologists received recommendations about how long to use anticoagulants, when to transfuse sickle cell patients, and when to perform surveillance scans in patients with early stage chronic lymphocytic leukemia (CLL), as the American Society of Hematology (ASH) issued its second list of tests and treatments to question under the 

	This year’s list was announced at the start of the 2014 Annual Meeting of ASH that convened at the Moscone Center in San Francisco. The first round of recommendations, numbers 1 through 5, were announced December 4, 2013, at the last ASH meeting in New Orleans. Details of recommendations 6 through 10 were presented at a session December 8, 2014.

The American Society of Hematology Annual Meeting, 2014

Bigger Regulatory Challenges in Diagnostics Than in Therapeutics, Industry Expert Says

Data Show High Response Rate to Ibrutinib Combination for Patients With Hard-to-Treat MCL

Best of ASH Presentations: Platelets, Lenalidomide for MDS, and Sorafenib in AML

Improved Cancer Care Through Innovation

Payers Look to CER for Improved Healthcare Decisions

Results Project Savings for Payers With Novel Oral Anticoagulants

SPIRIT 2: Dasatinib Superior to Imatinib in Newly Diagnosed CML

CML Updates: Defining MMR and Results of the DASISION Trial

Sessions Report Phase 2 Results of Pomalidomide Combinations

Promising Results for Elotuzumab Presented in Session on Multiple Myeloma

Early Treatment, Monoclonal Antibodies Discussed in Multiple Myeloma

ASH Presents Second Round of Tests, Treatments to Question Under Choosing Wisely Initiative

Care Plans to Reduce Healthcare Utilization in Sickle Cell Disease

Poster Presentations Cover Therapeutic Options in CML

Healthcare Costs in Need of Solutions: Experts at ASH Agree

Session on Survivorship Outlines Surveillance Strategies in Non-Hodgkin Lymphoma

Ibrutinib Demonstrates Significant Responses for Patients With Hard-to-Treat CLL/SLL, Phase 2 Data Show

Study Suggests Method of Reducing Blood Clots Without Risking Bleeding