Debate: What Is Optimal First-Line Therapy for Chronic Lymphocytic Leukemia?

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In the era of newer, highly effective targeted therapies for chronic lymphocytic leukemia (CLL), experts debated whether there is still a role for chemoimmunotherapy in the first-line setting for the treatment of this disease. In general, targeted therapies are preferred as first-line treatment for all patients, with the exception of low-risk patients [younger, fit patients with mutated IGHV who are candidates for fludarabine/cyclophosphamide/rituximab (FCR)]. About 37% of low-risk patients experience long-term durable remissions and remain stable after treatment with FCR for many years. Advantages of FCR over small molecule inhibitors include cost, fixed duration treatment, and long-term survival benefit. Disadvantages are an etimated 5% risk of developing myelodysplastic syndrome or acute myeloid leukemia. Advantages of small molecule inhibitors are improvements in progression-free and overall survival and quality of life when compared with chemoimmunotherapy. Disadvantages of small molecule inhibitors are high cost and the need for continuous treatment. However, studies are underway to develop fixed duration regimens with combinations of small molecule inhibitors that aim to deepen remissions.

Disclosures: Dr. Shadman has disclosed that he has received grant/research support from AbbVie, Inc., Acerta Pharma, AstraZeneca Pharmaceuticals LP, BeiGene, Celgene Corporation, for Genentech, Inc., Gilead Sciences, Inc., Merck & Co., Mustang Bio, Pharmacyclics, Sunesis Pharmaceuticals, Inc., and TG Therapeutics; is a scientific advisor for AstraZeneca, AbbVie, Inc., ADC Therapeutics, AstraZeneca Pharmaceuticals LP, Atara Biotherapeutics, Cellectar Biosciences, Genentech, Pharmacyclics, Sound Biologics, and Verastem. Dr. Stephens has disclosed that she has received grant/research support from Acerta Pharma, Gilead Sciences, Inc., Juno Therapeutics, Inc., mingSight, Arqule, and Karyopharm Therapeutics; and consulting fees from Janssen Pharmaceutical Products, Pharmacyclics, Karyopharm, and Innate. Dr. Chavez has disclosed that he has received grant/research support from Merck & Co.; and consulting fees from Bayer HealthCare, BMS/Celgene, Karyopharm Therapeutics, Kite Pharma, MorphoSys AG, and Novartis Pharmaceuticals; and is on the Product/Speakers Bureau for AstraZeneca Pharmaceuticals LP, BeiGene, and Genentech, Inc. Dr. Ma has disclosed that she has received grant/research support from AbbVie, Inc., AstraZeneca, BeiGene, Janssen Pharmaceutica Products, LP, Juno Therapeutics, Inc., Pharmacyclics, and TG Therapeutics; is a scientific advisor for AstraZeneca, Genentech, Inc. and Kite Pharma; and is on the Product/Speakers Bureau for AstraZeneca Pharmaceuticals LP, BeiGene, Janssen Pharmaceutica, and Pharmacyclics. Dr. Zelenetz has disclosed that he has received grant/research support from BeiGene, Gilead Sciences, Inc., MEI Pharma Inc., and Roche Laboratories, Inc.; and consulting fees from Adaptive Biotechnologies Corporation, Amgen Inc., Celgene Corporation, Genentech, Inc./Roche Laboratories, Inc., Gilead Sciences, Inc., Janssen Pharmaceutica Products, LP, Novartis Pharmaceuticals Corporation, and Verastem Oncology; and is a scientific advisor for AbbVie, Inc., AstraZeneca Pharmaceuticals LP, Genentech, Inc., Gilead Sciences, Inc., MorphoSys AG, and Pharmacyclics.

Correspondence: Mazyar Shadman, MD, MPH, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, D5-396, Seattle, WA 98109. Email: mshadman@fredhutch.org; and Deborah M. Stephens, DO, Huntsman Cancer Institute at the University of Utah, 9060 Flint Way, Park City, UT 84098. Email: deborah.stephens@hci.utah.edu
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