Randomized comparison of ibrutinib versus ofatumumab in relapsed or refractory (R/R) chronic lymphocytic leukemia/small lymphocytic lymphoma: Results from the phase III RESONATE trial.

Leukemia, Myelodysplasia, and Transplantation
Session Type and Session Title: 
Oral Abstract Session, Leukemia, Myelodysplasia, and Transplantation
Abstract Number: 
J Clin Oncol 32:5s, 2014 (suppl; abstr LBA7008)
John C. Byrd, Jennifer R. Brown, Susan Mary O'Brien, Jacqueline Claudia Barrientos, Neil E. Kay, Nishitha M. Reddy, Steven E. Coutre, Constantine Tam, Stephen P. Mulligan, Ulrich Jäger, Steve Devereux, Paul M. Barr, Richard R. Furman, Thomas J. Kipps, Florence Cymbalista, Maria Fardis, Jesse S. McGreivy, Fong Clow, Danelle Frances James, Peter Hillmen; The Ohio State University, Columbus, OH; Dana-Farber Cancer Institute, Boston, MA; The University of Texas MD Anderson Cancer Center, Houston, TX; Hofstra North Shore-LIJ School of Medicine, Hempstead, NY; Mayo Clinic, Rochester, MN; Vanderbilt University Medical Center, Nashville, TN; Stanford Cancer Center, Stanford University School of Medicine, Stanford, CA; Peter MacCallum Cancer Centre and St. Vincent's Hospital, Melbourne, Australia; Royal North Shore Hospital, Sydney, Australia; Medical University of Vienna, Vienna, Austria; College Hospital, NHS Foundation Trust Denmark Hill, London, United Kingdom; University of Rochester Cancer Center, Rochester, NY; Presbyterian Hospital/Cornell Medical Center, New York, NY; University of California, San Diego, School of Medicine, San Diego, CA; Hôpital Avicenne, Paris, France; Pharmacyclics, Inc., Sunnyvale, CA; Pharmacyclics, Sunnyvale, CA; Pharmacyclics, Inc, Sunnyvale, CA; The Leeds Teaching Hospitals, St. James Institute of Oncology, Leeds, United Kingdom

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Abstract Disclosures


Background: Treatment options for CLL/ SLL patients (pts) who fail chemoimmunotherapy are limited. We report interim results from a phase III randomized study of ibrutinib (ibr), a first in class covalent BTK inhibitor, vs ofatumumab (ofa) in R/R CLL/SLL. The Data Monitoring Committee recommended this analysis be considered final, based on meeting the primary and a key secondary endpoint. Methods: R/R CLL/SLL pts who failed ≥1 therapy received 420 mg oral ibr daily until progression or IV ofa 300/2000mg for 12 doses. Primary endpoint was progression-free survival (PFS) assessed by an independent review committee (IRC). Secondary endpoints included overall survival (OS), IRC assessed overall response rate (ORR) and safety. Results: Of 391 pts enrolled (median age 67 years; 40% ≥70 years; 57% Rai stage III/IV disease; 30% del 17p), 195 were randomized to ibr and 196 to ofa. Ibr pts had median 3 prior therapies vs 2 for ofa. Median follow-up was 9.4 months (m). Ibr significantly lengthened PFS (median not reached vs 8.1 m; HR 0.215, CI 0.146–0.317, p<0.0001; 78.5% risk reduction), and significantly improved OS (median not reached; HR 0.434, CI 0.238–0.789, p=0.0049) compared with ofa. ORR was 42.6 vs 4.1% (p<0.0001) and ORR+PR with lymphocytosis was 62.6 vs 4.1% for ibr vs ofa. Similar effects were seen in del17p and purine analog refractory subsets. In each arm 2 pts had confirmed Richter’s transformation. Most frequent adverse events (AE) for ibr vs ofa were diarrhea (47.7 vs 17.8%) fatigue (27.7 vs 29.8%), and nausea (26.2 vs 18.3%). Atrial fibrillation was more frequent with ibr (5.1 vs 0.5%). Major hemorrhages were reported in 1.0 vs 1.6% for ibr vs ofa. Drug discontinuation due to AE was 4.1 vs 3.6% for ibr vs ofa. 86% of ibr pts were continuing treatment. 57 pts randomized to ofa with confirmed PD had initiated ibr at cross-over. Conclusions: Compared with ofa, ibr significantly improved PFS, OS and ORR in pts with R/R CLL/SLL. The safety profile was comparable with that previously reported (Byrd NEJM 2013). These results support ibr as a beneficial therapy for R/R CLL patients irrespective of del 17p or purine analog refractory disease. Clinical trial information: NCT01578707.