TY - JOUR
T1 - Single-agent ibrutinib for rituximab-refractory waldenström macroglobulinemia
T2 - Final analysis of the substudy of the phase III innovateTM trial
AU - Trotman, Judith
AU - Buske, Christian
AU - Tedeschi, Alessandra
AU - Matous, Jeffrey V.
AU - MacDonald, David
AU - Tam, Constantine S.
AU - Tournilhac, Olivier
AU - Ma, Shuo
AU - Treon, Steven P.
AU - Oriol, Albert
AU - Ping, Jerry
AU - Briso, Eva M.
AU - Arango-Hisijara, Israel
AU - Dimopoulos, Meletios A.
N1 - Funding Information:
This study was funded by Pharmacyclics LLC, an AbbVie Company.
Funding Information:
This study was funded by Pharmacyclics LLC, an AbbVie Company. We thank all the patients who participated in this trial and their families and Cindi Hoover, PhD, of ApotheCom for medical writing supported by Pharmacyclics LLC, an AbbVie Company. We also thank Bernhard Hauns, MD, PhD, for his contributions to the study and analyses. Pharmacyclics LLC, an AbbVie Company, sponsored and designed the study. Study investigators and their research teams collected the data. The sponsor confirmed data accuracy and performed analysis of the data.
Publisher Copyright:
© 2021 The Authors; Published by the American Association for Cancer Research
PY - 2021/11/15
Y1 - 2021/11/15
N2 - 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.
AB - 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.
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U2 - 10.1158/1078-0432.CCR-21-1497
DO - 10.1158/1078-0432.CCR-21-1497
M3 - Article
C2 - 34380643
AN - SCOPUS:85118854780
SN - 1078-0432
VL - 27
SP - 5793
EP - 5800
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 21
ER -