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Randomized phase 3 study of rituximab, cyclophosphamide, doxorubicin, and prednisone plus vincristine (R-CHOP) or bortezomib (VR-CAP) in newly diagnosed mantle cell lymphoma (MCL) patients (pts) ineligible for bone marrow transplantation (BMT).
Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).
Background: R-CHOP is standard therapy for newly diagnosed, BMT-ineligible MCL pts. Bortezomib (V) is approved in the US for relapsed MCL. This study evaluated whether replacing vincristine with V in R-CHOP improves outcomes in newly diagnosed, BMT-ineligible MCL pts (NCT00722137). Methods: Adults with treatment-naive, measurable stage II–IV MCL and ECOG PS 0–2 were randomized 1:1 (stratified by IPI score and disease stage) to 6–8 21-d cycles of rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, all IV d 1, and prednisone 100 mg/m2 PO d 1–5, plus V 1.3 mg/m2 IV d 1, 4, 8, 11 (VR-CAP) or vincristine 1.4 mg/m2(max 2 mg) IV d 1 (R-CHOP). Primary endpoint was PFS by independent radiology review (IRC); secondary endpoints included TTP, TTNT, OS, response by modified IWRC criteria, and safety. 486 pts were planned for 295 total PFS events, to provide 80% power (α=.05, 2-sided) to detect 40% PFS improvement with VR-CAP. Results: 487 pts were randomized (244 R-CHOP, 243 VR-CAP; median age 66 yrs, 74% male, 74% stage IV MCL, 54% IPI ≥3). Pts received a median of 6 cycles. After 40 mos’ median follow-up (298 PFS events), median PFS by IRC was 14.4 (R-CHOP) vs 24.7 mos (VR-CAP) (ITT analysis: HR=.63* [.50, .79], P<.001**). Secondary efficacy data are below. Rates of grade ≥3 AEs were 85% (R-CHOP) vs 93% (VR-CAP), serious AEs 30% vs 38%, discontinuations due to AEs 7% vs 9%, and on-treatment drug-related deaths 3% vs 2%. Conclusions: VR-CAP significantly prolonged PFS and consistently improved secondary efficacy endpoints vs R-CHOP in newly diagnosed, BMT-ineligible MCL pts, with additional but manageable toxicity. Clinical trial information: NCT00722137.
|Median outcomes, mos||R-CHOP||VR-CAP||HR*||P**|
|4-yr OS, %||54||64||–||–|
* Stratified Cox model (HR <1 favors VR-CAP). ** Stratified log-rank test. † Bone marrow and LDH verified. ‡ Stratified Mantel-Haenszel estimate (OR >1 favors VR-CAP). § Stratified Cochran-Mantel-Haenszel X2 test.