Single-Agent Ibrutinib for Rituximab-Refractory Waldenström Macroglobulinemia: Final Analysis of the Substudy of the Phase III InnovateTM Trial.

Abstract

PURPOSE:

The first report from the open-label substudy of the phase III iNNOVATE study (PCYC-1127; NCT02165397) demonstrated that single-agent ibrutinib was efficacious and well tolerated in patients with heavily pretreated, rituximab-refractory Waldenström macroglobulinemia. Results from the final analysis are now reported.

PATIENTS AND METHODS:

Ibrutinib 420 mg was administered once daily to patients (N = 31) who failed to achieve at least a minor response (MR) or who relapsed <12 months after their last rituximab-containing therapy. Endpoints included progression-free survival (PFS) and overall response rate (ORR; MR or better) per independent review committee, hemoglobin improvement, overall survival (OS), and safety; serum IgM was also assessed.

RESULTS:

After a median follow-up of 58 months (range: 9-61), median PFS was 39 months [95% confidence interval (CI): 25-not evaluable]; 60-month PFS rate was 40%. In MYD88L265P/CXCR4WHIM and MYD88L265P/CXCR4WT subtypes, median PFS was 18 months and not reached, respectively. In all patients, ORR was 87%; responses deepened over time with major response (≥ partial response) rates increasing from 61% at 6 months to 77% at 60 months. Median OS was not reached. Seventeen of 21 patients (81%) with baseline hemoglobin ≤11.0 g/dL had sustained hemoglobin improvement. Improvements in serum IgM levels were sustained, reaching a maximum median change of -37 g/L at 54 months. Ibrutinib maintained a manageable safety profile, with no new safety signals identified. There were no events of major hemorrhage or atrial fibrillation.

CONCLUSIONS:

In the final analysis from iNNOVATE, single-agent ibrutinib continued to show sustained efficacy in patients with heavily pretreated, rituximab-refractory Waldenström macroglobulinemia.

• Authors: Judith Trotman, Christian Buske, Alessandra Tedeschi, Jeffrey V Matous, David MacDonald, Constantine S Tam, Olivier Tournilhac, Shuo Ma, Steven P Treon, Albert Oriol, Jerry Ping, Eva M Briso, Israel Arango-Hisijara, Meletios A Dimopoulos
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 27 Issue 21 Pg. 5793-5800 (11 01 2021) ISSN: 1557-3265 [Electronic] United States
• PMID: 34380643 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: ©2021 The Authors; Published by the American Association for Cancer Research.

Chemical References

• Antineoplastic Agents, Immunological
• Piperidines
• ibrutinib
• Rituximab
• Adenine

Topics

• Adenine (analogs & derivatives, therapeutic use)
• Aged
• Aged, 80 and over
• Antineoplastic Agents, Immunological (therapeutic use)
• Humans
• Middle Aged
• Piperidines (therapeutic use)
• Rituximab (therapeutic use)
• Treatment Failure
• Waldenstrom Macroglobulinemia (drug therapy)