P-164: Safety of lenalidomide (LEN)-based therapy vs non–LEN-based therapy for transplant-ineligible newly diagnosed multiple myeloma (TNE NDMM): update from the post-authorization study MM-034

Abstract

<h3>Background</h3> LEN-based therapy (tx) until progression is a standard approach for treating TNE NDMM. Several phase 3 trials including FIRST and SWOG S0777 have shown the safety and efficacy of LEN-based tx in this setting. This updated analysis from the ongoing, non-interventional, post-authorization study MM-034 (NCT03106324) further assessed the safety of LEN-based tx (including LEN + dexamethasone [Rd] and Rd + bortezomib [RVd]) vs non–LEN-based tx (including bortezomib + melphalan/prednisone [VMP]) in patients (pts) with TNE NDMM. <h3>Methods</h3> Pts in MM-034 had TNE NDMM and were initiating first-line tx or had received <2 cycles of tx. Tx was determined before enrollment per routine clinical practice. Pts were observed while on tx for ≤3 y, with 5 y of total follow-up. Primary endpoint was incidence of cardiovascular events. Secondary endpoints included incidence of infections and second primary malignancies, and further safety characterization. <h3>Results</h3> As of data cutoff (May 19, 2021), 451 pts who received LEN (Rd, n=378; RVd, n=49) and 439 who received non-LEN (VMP, n=277) were enrolled. Median (range) follow-up was 15.7 mo (0.3–44.3) for LEN (Rd 15.7 mo [0.3–44.3], RVd 15.2 mo [1.0–43.3]) and 15.2 mo (0.2–48.6) for non-LEN (VMP 15.9 mo [0.8–39.4]). Median age was 79 y (LEN) and 76 y (non-LEN); 52% and 62% of pts were male. More pts remained on tx with LEN (45% [Rd 44%, RVd 45%]) than non-LEN (21% [VMP 22%]). Rates of discontinuation of LEN vs non-LEN due to adverse events (AEs; 18% [Rd 19%, RVd 16%] vs 14% [VMP 12%]) and disease progression (9% [Rd 9%, RVd 10%] vs 9% [VMP 10%]) were similar. Among pts with ≥2 y of follow-up, median tx duration was longer with LEN (23.0 mo [Rd 23.5 mo, RVd 19.8 mo]) vs non-LEN (10.4 mo [VMP 10.8 mo]). Similar proportions of pts had cardiac AEs in the LEN (13% [Rd 13%, RVd 10%]) and non-LEN (11% [VMP 10%]) cohorts, including atrial fibrillation (4% vs 4%) and cardiac failure (3% vs 2%). Grade 3/4 tx-emergent AEs (TEAEs) were reported in 52% of pts with LEN (Rd 52%, RVd 59%) and 45% with non-LEN (VMP 42%). The most frequent grade 3/4 hematologic TEAEs (LEN [Rd, RVd] vs non-LEN [VMP]) were neutropenia (10% [11%, 8%] vs 9% [10%]), anemia (6% [6%, 4%] vs 5% [4%]), and thrombocytopenia (5% [5%, 4%] vs 7% [8%]). Grade 3/4 infections occurred in 14% of pts with LEN (Rd 12%, RVd 20%) vs 10% of pts with non-LEN (VMP 8%), including pneumonia (3% vs 3%). Grade 3/4 thromboembolic events occurred in 1% (LEN) and 0% (non-LEN) of pts. Incidence of any-grade peripheral neuropathy was 4% with LEN (Rd 2%, RVd 18%) vs 6% with non-LEN (VMP 8%). <h3>Conclusions</h3> Updated results of this ongoing non-interventional study continue to show that the safety profile of LEN-based tx in pts with TNE NDMM is similar to those from randomized controlled trials. Duration of tx was twice as long in LEN than non-LEN cohorts, but incidences of grade 3/4 TEAEs were similar. No new safety signals for LEN-based tx, including Rd and RVd, were identified.