Sustained efficacy and detailed clinical follow-up of first-line ibrutinib treatment in older patients with chronic lymphocytic leukemia: extended phase 3 results from RESONATE-2

• Published in: Haematologica (Roma) Vol. 103; no. 9; pp. 1502 - 1510
• Main Authors: Barr, Paul M., Robak, Tadeusz, Owen, Carolyn, Tedeschi, Alessandra, Bairey, Osnat, Bartlett, Nancy L., Burger, Jan A., Hillmen, Peter, Coutre, Steven, Devereux, Stephen, Grosicki, Sebastian, McCarthy, Helen, Li, Jianyong, Simpson, David, Offner, Fritz, Moreno, Carol, Zhou, Cathy, Styles, Lori, James, Danelle, Kipps, Thomas J., Ghia, Paolo
• Format: Journal Article
• Language: English
• Published: Italy Ferrata Storti Foundation 01.09.2018
• Subjects: Aged; Aged, 80 and over; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biomarkers, Tumor; Female; Follow-Up Studies; Humans; Leukemia, Lymphocytic, Chronic, B-Cell - diagnosis; Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy; Leukemia, Lymphocytic, Chronic, B-Cell - genetics; Male; Molecular Targeted Therapy; Mutation; Neoplasm Staging; Prognosis; Protein Kinase Inhibitors - administration & dosage; Protein Kinase Inhibitors - adverse effects; Protein Kinase Inhibitors - therapeutic use; Pyrazoles - administration & dosage; Pyrazoles - adverse effects; Pyrazoles - therapeutic use; Pyrimidines - administration & dosage; Pyrimidines - adverse effects; Pyrimidines - therapeutic use; Treatment Outcome
• ISSN: 0390-6078; 1592-8721; 1592-8721
• DOI: 10.3324/haematol.2018.192328

Results of RESONATE-2 (PCYC-1115/1116) supported approval of ibrutinib for first-line treatment of chronic lymphocytic leukemia. Extended analysis of RESONATE-2 was conducted to determine long-term efficacy and safety of ibrutinib in older patients with chronic lymphocytic leukemia. A total of 269 patients aged ≥65 years with previously untreated chronic lymphocytic leukemia without del(17p) were randomized 1:1 to ibrutinib (n=136) or chlorambucil (n=133) on days 1 and 15 of a 28-day cycle for 12 cycles. Median ibrutinib treatment duration was 28.5 months. Ibrutinib significantly prolonged progression-free survival chlorambucil (median, not reached 15 months; hazard ratio, 0.12; 95% confidence interval, 0.07-0.20; <0.0001). The 24-month progression-free survival was 89% with ibrutinib (97% and 89% in patients with del[11q] and unmutated immunoglobulin heavy chain variable region gene, respectively). Progression-free survival rates at 24 months were also similar regardless of age (<75 years [88%], ≥75 years [89%]). Overall response rate was 92% (125/136). Rate of complete response increased substantially from 7% at 12 months to 18% with extended follow up. Greater quality of life improvements occurred with ibrutinib chlorambucil in Functional Assessment of Chronic Illness Therapy-Fatigue ( =0.0013). The most frequent grade ≥3 adverse events were neutropenia (12%), anemia (7%), and hypertension (5%). Rate of discontinuations due to adverse events was 12%. Results demonstrated that first-line ibrutinib for elderly patients with chronic lymphocytic leukemia provides sustained response and progression-free survival benefits over chemotherapy, with depth of response improving over time without new toxicity concerns. This trial was registered at and .