Single-agent ibrutinib for rituximab-refractory waldenström macroglobulinemia: Final analysis of the substudy of the phase III innovateTM trial

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)5793-5800
Number of pages8
JournalClinical Cancer Research
Volume27
Issue number21
DOIs
StatePublished - Nov 15 2021

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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