Fixed-duration ibrutinib plus venetoclax for first-line treatment of CLL: primary analysis of the CAPTIVATE FD cohort
Por:
Tam, CS, Allan, JN, Siddiqi, T, Kipps, TJ, Jacobs, R, Opat, S, Barr, PM, Tedeschi, A, Trentin, L, Bannerji, R, Jackson, S, Kuss, BJ, Moreno, C, Szafer-Glusman, E, Russell, K, Zhou, C, Ninomoto, J, Dean, JP, Wierda, WG, Ghia, P
Publicada:
2 jun 2022
Ahead of Print:
1 jun 2022
Resumen:
CAPTIVATE (NCT02910583) is an international phase 2 study in patients aged <= 70 years with previously untreated chronic lymphocytic leukemia (CLL). Results from the cohort investigating fixed-duration (FD) treatment with ibrutinib plus venetoclax are reported. Patients received 3 cycles of ibrutinib lead-in then 12 cycles of ibrutinib plus venetoclax (oral ibrutinib [420 mg/d]; oral venetoclax [5-week ramp-up to 400 mg/d]). The primary endpoint was complete response (CR) rate. Hypothesis testing was performed for patients without del(17p) with prespecified analyses in all treated patients. Secondary endpoints included undetectable minimal residual disease (uMRD) rates, progression-free survival (PFS), overall survival (OS), and safety. Of the 159 patients enrolled and treated, 136 were without del(17p). The median time on study was 27.9 months, and 92% of patients completed all planned treatment. The primary endpoint was met, with a CR rate of 56% (95% confidence interval [CI], 48-64) in patients without del(17p), significantly higher than the prespecified 37% minimum rate (P < .0001). In the all-treated population, CR rate was 55% (95% CI, 48-63); best uMRD rates were 77% (peripheral blood [PB]) and 60% (bone marrow [BM]); 24-month PFS and OS rates were 95% and 98%, respectively. At baseline, 21% of patients were in the high tumor burden category for tumor lysis syndrome (TLS) risk; after ibrutinib lead-in, only 1% remained in this category. The most common grade >= 3 adverse events (AEs) were neutropenia (33%) and hypertension (6%). First-line ibrutinib plus venetoclax represents the first all-oral, once-daily, chemotherapy-free FD regimen for patients with CLL. FD ibrutinib plus venetoclax achieved deep, durable responses and promising PFS, including in patients with high-risk features.
Filiaciones:
Tam, CS:
Peter MacCallum Canc Ctr, 305 Grattan St, Melbourne, Vic 3000, Australia
St Vincents Hosp, Melbourne, Vic, Australia
Univ Melbourne, Melbourne, Vic, Australia
Allan, JN:
Weill Cornell Med, New York, NY USA
Siddiqi, T:
City Hope Natl Med Ctr, 1500 E Duarte Rd, Duarte, CA 91010 USA
Kipps, TJ:
Univ Calif San Diego, Moores Canc Ctr, San Diego, CA 92103 USA
Jacobs, R:
Levine Canc Inst, Charlotte, NC USA
Opat, S:
Monash Univ, Clayton, Vic, Australia
Barr, PM:
Univ Rochester, Med Ctr, Wilmot Canc Inst, Rochester, NY 14642 USA
Tedeschi, A:
ASST Grande Osped Metropolitano Niguarda, Milan, Italy
Trentin, L:
Univ Padua, Padua, Italy
Bannerji, R:
Rutgers Canc Inst New Jersey, New Brunswick, NJ USA
Jackson, S:
Middlemore Hosp, Auckland, New Zealand
Kuss, BJ:
Flinders Univ & Med Ctr, Bedford Pk, SA, Australia
Moreno, C:
Autonomous Univ Barcelona, Hosp Santa Creu & St Pau, Barcelona, Spain
Szafer-Glusman, E:
Pharmacyclics LLC, Sunnyvale, CA USA
Russell, K:
Pharmacyclics LLC, Sunnyvale, CA USA
Zhou, C:
Pharmacyclics LLC, Sunnyvale, CA USA
Ninomoto, J:
Pharmacyclics LLC, Sunnyvale, CA USA
Dean, JP:
Pharmacyclics LLC, Sunnyvale, CA USA
Wierda, WG:
Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA
Ghia, P:
Univ Vita Salute San Raffaele, Milan, Italy
IRCCS Osped San Raffaele, Milan, Italy
hybrid, All Open Access; Hybrid Gold
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