CANOVA: Vd vs Pd for t(11;14)-positive RRMM

Results from the randomized, open-label, phase III CANOVA trial (NCT03539744), comparing venetoclax + dexamethasone (Vd) with pomalidomide + dexamethasone (Pd) in patients with translocation (t) (11;14)-positive relapsed/refractory multiple myeloma (RRMM; N = 263), were recently published in the Journal of Clinical Oncology by Popat et al. The primary endpoint was independent review committee (IRC)-assessed progression-free survival (PFS). Secondary endpoints included response rates, overall survival (OS), measurable residual disease (MRD) negativity, and safety.

Key data: At a median follow-up of 24.9 months, IRC-assessed median PFS was 9.9 months (95% confidence interval [CI], 6.9–12.6) with Vd and 5.8 months (95% CI, 3.8–9.2) with Pd (hazard ratio [HR], 0.823; 95% CI, 0.596–1.136; p = 0.24). The primary endpoint was not met. IRC-assessed overall response rate (ORR) was higher with Vd (62%; 95% CI, 53–70) than with Pd (35%; 95% CI, 27–44). MRD negativity rate (× 10⁻⁵) with complete response (CR) or better (n = 19) was 8% (95% CI, 4–13) with Vd and 0% (95% CI, 0–3) with Pd. Median OS was numerically higher with Vd than Pd (32.4 months vs 26.9 months; HR, 0.856; 95% CI, 0.612–1.197). Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 67% and 83% of patients receiving Vd and Pd, respectively.

Key learning: The combination of Vd did not demonstrate superiority in PFS compared with Pd in patients with t(11;14)-positive RRMM. However, Vd demonstrated higher response rates and greater depth of response, with numerically longer survival outcomes and a safety profile consistent with the known profiles of each agent.