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CLINICAL NEWS Latest & Greatest FDA Issues Draft Guidance on MRD in Clinical Trials To make drug development and evalu- ation more efficient, the U.S. Food and Drug Administration (FDA) issued draft guidance on the use of minimal residual disease (MRD) in the regulatory evalua- tion of treatments for hematologic malig- nancies. The agency’s guidance is based on feedback from workshops with sponsors, researchers, and regulators, as well as an analysis of marketing applications that showed inconsistent quality of MRD data. “We’re focused on making the process of generating pre-clinical and clinical evidence required for making risk-based regulatory decisions more modern, more scientifically rigorous, and more efficient,” FDA Commissioner Scott Gottlieb, MD, said in a statement announcing the new draft guidance. “[This document will] provide drug developers greater clarity and direction as they pursue the next generation of therapies and treatments for patients.” The new guidance, which is open for public comment, advised sponsors to design trials that address two main questions: “Is MRD as assessed (sample, timing, threshold, etc.) a clinically valid biomarker for the context of use (disease, disease status, type of therapy, etc.)?” and “Is the MRD assay used (or to be used) in the clinical trial analytically valid for the range of results that are important to the trial?” The guidance document also includes disease-specific considerations for the use of MRD in treatment evaluations. For more information about the draft guid- ance, visit www.fda.gov/Drugs/Guidance ComplianceRegulatoryInformation. Source: FDA news release, October 15, 2018. CMS Finalizes Physician Fee Schedule for 2019 The Centers for Medicare and Medicaid Services (CMS) released its final changes to the Medicare Physician Fee Schedule and the Quality Payment Program for 2019, which include substantial updates to coverage of telehealth services. The final- ized rule also revises proposed changes to evaluation and management (E/M) documentation requirements, based on overwhelming negative responses to the initial proposals. ASHClinicalNews.org “Today’s rule finalizes dramatic improvements for clinicians and patients and reflects extensive input from the medical community,” said CMS Adminis- trator Seema Verma. “[It] offers immedi- ate relief from onerous requirements that contribute to burnout in the medical pro- fession and detract from patient care.” For example, the new rule elimi- nates the requirement to document the medical necessity of home visits, and physicians will no longer be required to re-record elements of history and physi- cal exam when there is evidence that the information has been reviewed and updated. CMS estimates that the new rule will save clinicians $87 million in reduced administrative costs in 2019 and $843 million over the next decade. The agency also plans to continue its controversial site-neutral billing policies, which are designed to encourage fair competition between medical services provided by hospitals and those provided by physicians. The agency also is making changes to the Merit-based Incentive Payment System, expanding the list of eligible clinicians and adjusting which quality measures it uses to rate partici- pating physicians. “Today’s rule finalizes dramatic improvements for clinicians and patients and reflects extensive input from the medical community.” —SEEMA VERMA, CMS Administrator CMS will not implement any payment changes until January 1, 2021, which will allow the agency to collect stakeholder input to further refine payment policies. Source: CMS press release, November 1, 2018; American Society of Hematology Practice Update, November 8, 2018. FDA Approves Elotuzumab-Based Triplet Regimen for Myeloma The FDA approved the combination of elotuzumab plus pomalidomide and dexamethasone for the treatment of adult patients with relapsed or refractory mul- tiple myeloma (MM) who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor. The agency’s decision was based on results from the randomized, phase II ELOQUENT-3 trial, which compared the elotuzumab combination with pomalido- mide and dexamethasone alone. After a median follow-up of 10.25 months (range not reported), the triplet therapy doubled both median progression-free survival (PFS; 10.25 months vs. 4.67 months; p=0.008) and overall response rate (53.3% vs. 26.3%; p=0.003). This included a higher rate of very good partial responses or better in the elotuzumab group (20% vs. 9%; p value not provided). Serious adverse events (AEs) were reported in 22 percent of patients treated with the triplet therapy and in 15 percent of patients in the control arm. AEs led to treatment discontinuation of any drug in 5 percent of patients in the elotuzumab arm and 1.8 percent in the pomalidomide- dexamethasone arm. Elotuzumab, an anti-SLAMF7 antibody, was previously approved in combination with lenalidomide and dexa- methasone for the treatment of patients with MM who have received one to three prior therapies. Source: Bristol-Myers Squibb press release, November 6, 2018; FDA approval letter, November 6, 2018. FDA Expands Brentuximab Vedotin’s Indication Brentuximab vedotin has been approved in combination with chemotherapy for the firstline treatment of adult patients with certain peripheral T-cell lymphomas (PTCLs). The FDA granted this application pri- ority review and breakthrough therapy designation, and this is the first approval for this indication. The agency issued its decision through an expedited review process for oncology products, the Real-Time Oncology Re- view (RTOR) program. “[This program] allows the FDA to access key data prior to the official submission of the application allowing the review team to begin their review earlier and communicate with the sponsor prior to the application’s actual submission,” explained Richard Pazdur, MD, director of the FDA’s Oncology Cen- ter of Excellence and acting director of the Office of Hematology and Oncology Products. “When the sponsor submits the completed application, the review team will already be familiar with the data and be able to conduct a more efficient, timely and thorough review. RTOR allowed the FDA to approve this indication within two weeks of the completed application’s submission.” “[The Real-Time Oncology Review program] allows the FDA to access key data prior to the official submission of the application.” —RICHARD PAZDUR, MD The decision was based on data from a clinical trial of 452 patients with certain PTCLs who received either brentuximab vedotin plus chemotherapy or chemo- therapy alone. Median PFS was signifi- cantly longer in the brentuximab vedotin group (48 months vs. 21 months [ranges not provided]; p=0.01). The most common AEs associated with brentuximab vedotin included peripheral neuropathy, nausea and vomiting, diarrhea, leukopenia, fatigue, mouth sores, constipation, hair loss, fever, and anemia. The prescribing informa- tion for brentuximab vedotin includes a boxed warning about the risk of a fatal or life-threatening progressive multifocal leukoencephalopathy. Brentuximab vedotin was previously approved for the treatment of adult pa- tients with previously untreated stage III or IV classical Hodgkin lymphoma. ● Source: FDA news release, November 16, 2018. ASH Clinical News 17