Citations 1
Venetoclax-Dexamethasone Versus Pomalidomide-Dexamethasone in t(11;14)-Positive Relapsed/Refractory Multiple Myeloma: Primary Results of the Randomized, Phase III CANOVA Study
Popat, Rakesh , Beksaç, Meral , Gatt, Moshe E. , Gay, Francesca , Jo, Jae‐Cheol , Kapoor, Prashant , Katodritou, Eirini , Kortüm, K. Martin , Ling, Silvia , Nagarajan, Chandramouli , Suzuki, Kenshi , Qiu, Lugui , Onishi, Maika, Ku, Grace , Ross, Jeremy A. , Badawi, Mohamed , Fusco, Mary Jean, Dobkowska, Edyta, Arriola, Emma, Bueno, Orlando F. , Iida, Shinsuke , Valent, Jason , Mateos, María‐Victoria , Dimopoulos, Meletios A , Gatt, Moshe E , Gay, Francesca , Jo, Jae-Cheol , Kapoor, Prashant , Katodritou, Eirini , Kortüm, Martin , Ling, Silvia , Nagarajan, Chandramouli , Ku, Grace , Dail, Monique , Bahlis, Nizar Jacques , Iida, Shinsuke , Mateos, María-Victoria , Beksac, Meral , Popat, Rakesh , Dimopoulos, Meletios Α. , Dail, Monique , Mukherjee, Nabanita, Moreau, Philippe , Valent, Jason Neil
Journal of Clinical Oncology | December 10, 2025 | Volume: 44 | Issue: 3 | Pages: 164-175
PURPOSE Venetoclax, an oral BCL-2 inhibitor, has efficacy in t(11;14)-positive relapsed/refractory multiple myeloma (RRMM), which is enhanced by dexamethasone, which promotes BCL-2 dependency. METHODS The randomized, open-label, phase III CANOVA study (ClinicalTrials.gov identifier: NCT03539744 ) enrolled adults with t(11;14)-positive RRMM who had received ≥2 previous lines of therapy. Patients were randomly assigned (1:1) to venetoclax-dexamethasone or pomalidomide-dexamethasone until progression or intolerable toxicity. The primary end point was independent review committee assessed–progression-free survival (PFS) in the intention-to-treat population analyzed by stratified log-rank test (two-sided type I error rate, α = .05), with hazard ratio (HR) and 95% CI estimated by stratified Cox proportional hazard model. Secondary end points included response rates, overall survival (OS), minimal residual disease (MRD) negativity rate (<10 –5 ), and safety. RESULTS Overall, 263 patients were randomly assigned (venetoclax-dexamethasone, n = 133; pomalidomide-dexamethasone, n = 130). Median PFS was 9.9 months (95% CI, 6.9 to 12.6) with venetoclax-dexamethasone versus 5.8 months (95% CI, 3.8 to 9.2) with pomalidomide-dexamethasone (HR, 0.823 [95% CI, 0.596 to 1.136]; P = .24). Overall response and very good partial response or better rates were 62% and 39%, respectively, with venetoclax-dexamethasone versus 35% and 14% with pomalidomide-dexamethasone. MRD negativity rate was 8% with venetoclax-dexamethasone and 0% with pomalidomide-dexamethasone. Median OS was 32.4 months (95% CI, 26.4 to 40.7) with venetoclax-dexamethasone and 26.9 months (95% CI, 20.4 to 38.9) with pomalidomide-dexamethasone (HR, 0.856 [95% CI, 0.612 to 1.197]). Grade ≥3 treatment-emergent adverse event rates were 67% with venetoclax-dexamethasone versus 83% with pomalidomide-dexamethasone. There were 16 (12%) treatment-emergent deaths with venetoclax-dexamethasone versus 8 (6%) with pomalidomide-dexamethasone. CONCLUSION The primary end point of PFS was not met. PFS and OS were numerically longer with venetoclax-dexamethasone versus pomalidomide-dexamethasone in t(11;14)-positive RRMM. Consistent with previous studies, infections were associated with venetoclax-dexamethasone; no new safety signals were observed.