Phase III CANOVA Study: Biomarker Subgroup Analysis in Advanced Multiple Myeloma

By: Vanessa A. Carter, BS
Posted: Monday, August 5, 2024

Nizar J. Bahlis, MD, of Arnie Charbonneau Cancer Institute, University of Calgary, Alberta, Canada, and colleagues performed the phase III CANOVA study to evaluate the use of dexamethasone combined with either venetoclax or pomalidomide in patients with t(11;14)-positive relapsed or refractory multiple myeloma. Although the primary endpoint of median progression-free survival was not reached at the primary analysis, positive results from the correlative biomarker analysis were presented during the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 7510).

The global, open-label, phase III CANOVA study enrolled 263 patients with t(11;14)-positive relapsed or refractory multiple myeloma who received at least two prior lines of therapy. Participants were randomly assigned 1:1 to receive dexamethasone plus either venetoclax (n = 133) or pomalidomide (n = 130). Endpoints included median progression-free survival, objective response rate, median overall survival, undetectable measurable residual disease (MRD) status, and rates of at least a very good partial response. BCL2 expression was defined as either BCL2-high or BCL2-low, and chromosome 1q abnormalities were characterized as normal, gain, or amplified.

Progression-free survival and median overall survival were similar among patients given venetoclax plus dexamethasone regardless of BCL2 status. Rates of objective response, undetectable MRD status, and at least a very good partial response were numerically higher among patients in the BCL2-high subgroup. Of note, those in the BCL2-low subgroup who received pomalidomide had numerically longer progression-free survival and overall survival than did participants treated with venetoclax.

Chromosome 1q abnormalities were detected at similar rates across the BCL2-high and BCL2-low subgroups in the venetoclax arm (51% vs 45%) but not in the pomalidomide arm (59% vs 31%). Patients with normal chromosome 1q and gain(1q) genotypes experienced improved survival, response, and undetectable MRD status with venetoclax; those with amplification of 1q demonstrated poor outcomes regardless of treatment.

Disclosure: For full disclosures of the study authors, visit coi.asco.org.

2024 ASCO Annual Meeting

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