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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).
J Clin Oncol 32:5s, 2014 (suppl; abstr 8500)
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.