OA-52: Results From the Randomized, Open-Label Phase 3 CANOVA Study of Venetoclax-Dexamethasone Versus Pomalidomide-Dexamethasone in Patients With t(11;14)-Positive Relapsed/Refractory Multiple Myeloma

Introduction: Although multiple myeloma (MM) is characterized by well-defined genetic aberrations such as t(11;14), biomarker-directed therapies are lacking. Patients (pts) with t(11;14) MM have higher BCL-2 levels, and treatment with the potent BCL-2 inhibitor venetoclax has shown efficacy and safety in pts with t(11;14) relapsed/refractory MM (RRMM; Kumar, Blood. 2017;130:2401. Kumar, Lancet Oncol. 2020;21:1630). The randomized, multicenter, open-label Phase 3 CANOVA study (NCT03539744) is evaluating venetoclax and dexamethasone vs pomalidomide and dexamethasone in pts with t(11;14) RRMM. Here, we report patient aggregate characteristics, with randomized efficacy and safety forthcoming for presentation.

Methods: Eligible pts were aged ≥18 years and had t(11;14)-positive RRMM per centralized FISH with plasma cell enrichment, an ECOG performance status (ECOG PS) ≤2, received ≥2 prior lines of therapy (LOTs), progressed on or within 60 days after completing their last LOT, previously received a proteasome inhibitor (PI), and were refractory to or relapsed on lenalidomide. Pts were randomized 1:1 to venetoclax (800 mg PO QD, no dose ramp-up) or pomalidomide (4 mg PO Days 1–21) added to dexamethasone (40 mg QW) for each 28-day cycle, with stratification based on age at randomization ( < 65 vs ≥65 years), prior LOTs (2 to 3 vs ≥4), and International Staging System (ISS) stage at screening (I vs II vs III). The primary endpoint is progression-free survival per independent review committee (IRC) assessment. Key secondary endpoints include overall response rate per IRC, rate of very good partial response or better per IRC, overall survival, minimal residual disease negativity rate, and patient-reported outcomes.

Results: At a median 21.9 months of follow-up (March 16, 2023 cutoff), 260 pts were randomized and 254 were treated; 109 pts (42%) had discontinued the study. The median age was 66.5 years (range, 37–89), and 57% of pts were aged ≥65 years. 57% of pts were male. Patient-reported race included White (68%), Asian (30%), Black or African American (1%), and Native Hawaiian or Other Pacific Islander (0.4%), and 4% of pts reported Hispanic or Latino ethnicity. Most pts had an ECOG PS of 0 (48%) or 1 (44%). At screening, 74% of pts had received 2 to 3 prior LOTs and 26% had received ≥4 prior LOTs; 48%, 33%, and 19% of pts were ISS stage I, II, or III, respectively. Most pts were refractory to PIs (77%) and immunomodulatory drugs (97% [lenalidomide, 96%]), and more than a third refractory to anti-CD38 monoclonal antibodies (37%). Per IMWG consensus, 92% of evaluable pts were standard risk and 8% were high risk. Randomized results from the event-driven primary analysis will be presented at the meeting.

Conclusions: The CANOVA study is evaluating treatment with once-daily oral venetoclax added to dexamethasone, which represents the potential for the first biomarker-directed therapy for pts with t(11;14) RRMM. Primary analysis results from this randomized Phase 3 study will be presented at the meeting.