2017 ASCO Annual Meeting!
Session: Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia
Type: Oral Abstract Session
Time: Saturday June 3, 3:00 PM to 6:00 PM
A genetic risk-stratified, randomized phase 2 intergroup study of fludarabine/antibody combinations in symptomatic, untreated chronic lymphocytic leukemia (CLL): Results from Cancer and Leukemia Group B (CALGB) 10404 (Alliance).
Chronic Lymphocytic Leukemia (CLL)
Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia
2017 ASCO Annual Meeting
J Clin Oncol 35, 2017 (suppl; abstr 7503)
Author(s): Amy S. Ruppert, John C. Byrd, Nyla A. Heerema, Mitchell Reed Smith, John E. Godwin, Stephen Couban, Todd A. Fehniger, Michael Thirman, Alese E. Halvorson, Martin S. Tallman, Frederick R. Appelbaum, Richard M. Stone, Sue Robinson, Julie E. Chang, Sumithra J. Mandrekar, Richard A. Larson; The Ohio State University, Columbus, OH; The Ohio State University Comprehensive Cancer Center, Columbus, OH; Cleveland Clinic, Cleveland, OH; Providence Medical Group, Portland, OR; Queen Elizabeth II Health Sciences Centre, Halifax, NS, Canada; Washington University in St. Louis, St. Louis, MO; University of Chicago, Chicago, IL; Mayo Clinic, Rochester, MN; Department of Medicine, Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, NY; Fred Hutchinson Cancer Research Center, Seattle, WA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA; Wisconsin Institute for Medical Research, Madison, WI
Background: Prior to use of novel targeted agents for CLL, debate existed regarding the best chemoimmunotherapy regimen to build upon in patients (pts) with non-del(11q) disease. The role of lenalidomide (L) was also not defined. CALGB 10404 was a randomized phase 2 study addressing these questions. Methods: Pts with untreated CLL requiring therapy were randomized to treatment with fludarabine + rituximab (FR), FR + 6 monthly consolidative treatments of L (5 mg days 1-21/28 x 1 then 10 mg days 1-21/28 x 5) (FR+L), or FR + cyclophosphamide (FCR). Based on pretreatment central interphase cytogenetic screening, pts with del(11q22.3) in at least 20% of cells were excluded from the primary analysis, testing whether 2-year progression-free survival (PFS) rate was improved in non-del(11q) pts within each arm. A target accrual of 103 non-del(11q) pts per arm provided at least 84% power to detect an increase in 2-year PFS rate from 60% to 73%; the critical value was 69% using a single stage design and type I error rate of 4%. Results: A total of 342 non-del(11q) CLL pts were randomized to treatment with FR (n = 123), FR+L (n = 109), or FCR (n = 110). Baseline characteristics were similar across arms. Two-year PFS rates with exact 90% CIs were 64% (57-71%) (FR), 71% (63-78%) (FR+L), and 74% (66-80%) (FCR). Median PFS was significantly shorter with FR compared to FR+L (p = 0.03) and FCR (p < 0.01): 43 (95% CI: 33-50), 66 (95% CI: 45-not reached), and 78 (95% CI: 58-not reached) months respectively. Median overall survival (OS) has not been reached for any arm. OS at 1, 2, and 3 years was similar across arms, although there was a plateau in OS with no events beyond 41 months in the FR+L arm, different from FR/FCR where events continued to occur. The most common adverse events were cytopenias and infections. Conclusions: FR+L and FCR met the protocol defined primary endpoint. FR+L extended PFS relative to FR and a plateau in survival differentiated this arm from the FR/FCR arms. Future studies comparing FR+L to FCR or incorporating L into other novel treatment regimens are justified. Support: U10CA180821, U10CA180882, Celgene. Clinical trial information: NCT00602459
Meeting: 2017 ASCO Annual Meeting Abstract No: 7505 First Author: Matthew Steven Davids