Abstract
e20524 Background: The BELLINI trial investigated the efficacy and safety of venetoclax (ven)/bortezomib (bort)/dexamethasone (dex) vs placebo/bort/dex in patients with bort-sensitive, early relapsed myeloma. The median PFS favored the ven arm (22.4 vs 11.5 months); however, a higher death rate in the ven arm led to study discontinuation. A subgroup of patients with t(11;14) not only had improved PFS but a positive trend in OS with ven, suggesting biomarker-driven patient selection may mitigate the safety concern. BELLIINI results raised concern regarding the natural history of myeloma progressing on ven. We aimed to investigate the clinical outcomes of ven refractory myeloma patients. Methods: We identified 70 refractory myeloma patients at our institution prescribed ven alone or in combination between 03/2014 -11/2019. Our group has published the functional profiling of BCL2 family members to predict responses to ven (Matulis, S et al. Leukemia), and most patients had functional profiling available prior to starting ven. Demographic and outcomes data were obtained from our IRB approved myeloma database and responses were evaluated per IMWG criteria. Results: Patients received a median of 3 (1-13) lines of therapy (LOT), with 37% receiving ≥4prior LOT and 86% had t(11;14) by FISH/CTG. Most patients received ASCT (86%) and were refractory to len and bort (97%), dara (41.4%), car (43%), or pom (53%). The most common combinations with ven were dex (83%), PI and dex (8.5%), or dara and dex (8.5%). At a median follow up of 16.8 months, 38 patients progressed on ven. Median duration of therapy was 9.5 (1-63) months. Median PFS for the entire cohort was 13 (7.9-18.2) months. Use of ven as an early LOT provided PFS benefit ( < 3 vs > 3 LOT: 23.2 vs 10.4 months). Notably, patients who received > 6 LOT also had a PFS benefit of 7.23 (0-15.6) months, and ‘penta-refractory’ patients had a PFS of 7.2 (0-17.2) months. Among the 38 patients that progressed on ven, dara-based combinations (30%) and clinical trials (24%) were the most common subsequent LOT. At a median follow up of 15.4 months, the median OS for the cohort from the time of ven refractoriness was 31.4 months. Patients who received > 6 LOT had an OS of 15.1 (0-14.2) months and ‘penta-refractory’ patients at ven refractoriness had an OS of 13.7 (0-30.6) months. Conclusions: Patients with ven refractory myeloma can still experience good long term outcomes, and our experience does not support the hypothesis that ven resistance leads to a more refractory myeloma phenotype. These data support the early use of ven or ven combinations in the t(11;14) cohort of patients.
Published Version
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