Final analysis from RESONATE: Up to six years of follow‐up on ibrutinib in patients with previously treated chronic lymphocytic leukemia or small lymphocytic lymphoma

Ibrutinib, a once‐daily oral inhibitor of Bruton's tyrosine kinase, is approved in the United States and Europe for treatment of patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). The phase 3 RESONATE study showed improved efficacy of single‐agent ibrutinib ov...

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Bibliographic Details
Published in:American journal of hematology 2019-12, Vol.94 (12), p.1353-1363
Main Authors: Munir, Talha, Brown, Jennifer R., O'Brien, Susan, Barrientos, Jacqueline C., Barr, Paul M., Reddy, Nishitha M., Coutre, Steven, Tam, Constantine S., Mulligan, Stephen P., Jaeger, Ulrich, Kipps, Thomas J., Moreno, Carol, Montillo, Marco, Burger, Jan A., Byrd, John C., Hillmen, Peter, Dai, Sandra, Szoke, Anita, Dean, James P., Woyach, Jennifer A.
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal, Humanized - therapeutic use
Antineoplastic Agents, Immunological - therapeutic use
Bone marrow
Bruton's tyrosine kinase
Cardiovascular Diseases - chemically induced
Chronic lymphocytic leukemia
Enzyme inhibitors
Female
Fibrillation
Follow-Up Studies
Hematologic Diseases - chemically induced
Hematology
Humans
Infections - etiology
Kaplan-Meier Estimate
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy
Leukemia, Lymphocytic, Chronic, B-Cell - genetics
Lymphatic leukemia
Lymphoma
Male
Middle Aged
p53 Protein
Patients
Progression-Free Survival
Protein Kinase Inhibitors - adverse effects
Protein Kinase Inhibitors - therapeutic use
Protein-tyrosine kinase
Pyrazoles - adverse effects
Pyrazoles - therapeutic use
Pyrimidines - adverse effects
Pyrimidines - therapeutic use
Remission Induction
Risk
Salvage Therapy
Survival
Targeted cancer therapy
Treatment Outcome
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Summary:Ibrutinib, a once‐daily oral inhibitor of Bruton's tyrosine kinase, is approved in the United States and Europe for treatment of patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). The phase 3 RESONATE study showed improved efficacy of single‐agent ibrutinib over ofatumumab in patients with relapsed/refractory CLL/SLL, including those with high‐risk features. Here we report the final analysis from RESONATE with median follow‐up on study of 65.3 months (range, 0.3‐71.6) in the ibrutinib arm. Median progression‐free survival (PFS) remained significantly longer for patients randomized to ibrutinib vs ofatumumab (44.1 vs 8.1 months; hazard ratio [HR]: 0.148; 95% confidence interval [CI]: 0.113‐0.196; P˂.001). The PFS benefit with ibrutinib vs ofatumumab was preserved in the genomic high‐risk population with del(17p), TP53 mutation, del(11q), and/or unmutated IGHV status (median PFS 44.1 vs 8.0 months; HR: 0.110; 95% CI: 0.080‐0.152), which represented 82% of patients. Overall response rate with ibrutinib was 91% (complete response/complete response with incomplete bone marrow recovery, 11%). Overall survival, censored for crossover, was better with ibrutinib than ofatumumab (HR: 0.639; 95% CI: 0.418‐0.975). With up to 71 months (median 41 months) of ibrutinib therapy, the safety profile remained consistent with prior reports; cumulatively, all‐grade (grade ≥3) hypertension and atrial fibrillation occurred in 21% (9%) and 12% (6%) of patients, respectively. Only 16% discontinued ibrutinib because of adverse events (AEs). These long‐term results confirm the robust efficacy of ibrutinib in relapsed/refractory CLL/SLL irrespective of high‐risk clinical or genomic features, with no unexpected AEs. This trial is registered at www.clinicaltrials.gov (NCT01578707).
ISSN:0361-8609
1096-8652
DOI:10.1002/ajh.25638