CHICAGO, IL—A regimen containing bortezomib significantly prolonged progression-free survival (PFS) compared with a vincristine-based regimen, a phase 3 study in patients with newly diagnosed mantle cell lymphoma (MCL) ineligible for bone marrow transplantation (BMT) reported at the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting has found.
The R-CHOP (rituximab, cyclophosphamide, doxorubicin, and prednisone plus vincristine) regimen is standard therapy for this patient population, while bortezomib is approved in the United States for relapsed MCL. In this study, Franco Cavalli, MD, of the Oncology Institute of Southern Switzerland, Bellinzona, Switzerland, and the LYM-3002 Investigators sought to determine whether replacing vincristine with bortezomib (VR-CAP) improved outcomes.
The study randomly assigned 487 patients with treatment-naïve, measurable stage II–IV MCL and Eastern Cooperative Oncology Group performance status 0 to 2, stratified by International Prognostic Index (IPI) score and disease stage, to six to eight 21-day cycles of intravenous rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, and doxorubicin 50 day 1, and oral prednisone 100 mg/m2 days 1 to 5, plus intravenous bortezomib 1.3 mg/m2 days 1, 4, 8, and 11 (VR-CAP; n=243), or intravenous vincristine 1.4 mg/m2(maximum 2 mg) day 1 (R-CHOP; n=244).
The primary endpoint was PFS as evaluated by independent radiology review. Secondary endpoints included time to and duration of response, duration of complete response (CR) and unconfirmed CR, time to progression (TTP), time to next treatment (TTNT), treatment-free interval, overall survival (OS), response by modified International Workshop Response Criteria, and safety.
To provide 80% power (α = 0.05, two-sided) to detect a 40% improvement in PFS with VR-CAP, 486 patients were planned for a total of 295 total PFS events.
Median age of the patients was 66 years in the R-CHOP arm and 65 years on the VR-CAP arm, 75%/73% were male, 74%/75% had stage IV MCL, and 55%/54% had an IPI score of 3 or higher. A median of six cycles was administered, and less than 20 patients in each arm discontinued treatment before the planned end of study. After 40 months of median follow-up (298 events), median PFS by independent radiology review was 14.4 months for the R-CHOP arm compared with 24.7 months for the VR-CAP arm (intent-to-treat analysis hazard ratio [HR], 0.63; 95% CI: 0.50-0.79]; P < 0.001). Median PFS by investigator review was 16.1 months for the R-CHOP arm versus 30.7 months for the VR-CAP arm (HR, 0.51; P < 0.001).