TY - JOUR
TI - Single-Agent Ibrutinib for Rituximab-Refractory Waldenstrom
Macroglobulinemia: Final Analysis of the Substudy of the Phase III
Innovate (TM) Trial
AU - Trotman, Judith
AU - Buske, Christian
AU - Tedeschi, Alessandra and
AU - Matous, Jeffrey V.
AU - MacDonald, David
AU - Tam, Constantine S. and
AU - Tournilhac, Olivier
AU - Ma, Shuo
AU - Treon, Steven P.
AU - Oriol, Albert
AU - and Ping, Jerry
AU - Briso, Eva M.
AU - Arango-Hisijara, Israel and
AU - Dimopoulos, Meletios A.
JO - Clinical Cancer Research
PY - 2021
VL - 27
TODO - 21
SP - 5793-5800
PB - AMER ASSOC CANCER RESEARCH
SN - 1078-0432
TODO - 10.1158/1078-0432.CCR-21-1497
TODO - null
TODO - 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 Waldenstrom 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 MYD88(L265P)/CXCR4(WHIM) and
MYD88(L265P)/CXCR4(WT) 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 similar to 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 showsustained efficacy in patients with heavily pretreated,
rituximab-refractory Waldenstrom macroglobulinemia.
ER -