Thromboembolic events in immunomodulatory drug (IMiD)–sparing regimens for patients with newly diagnosed multiple myeloma (NDMM).

Abstract

e19530 Background: Patients (pts) with NDMM treated with IMiD-based regimens have an increased risk of thromboembolic events (TE). In the MAIA study with transplant (ASCT) ineligible (TIE) NDMM pts, the cumulative rates of TE were 18% and 19% in the dara-containing and dara-free arms, respectively. Despite high rate of thromboprophylaxis (tpx) utilization (>80%) in the GRIFFIN study with ASCT eligible NDMM pts, the rates of venous TE (VTE) were 10.1% and 15.7%, in the dara-containing and dara-free arms, respectively. Both studies highlight concerningly elevated TE incidence in NDMM pts treated with IMiD-containing regimens. Rates of TE, however, in NDMM pts treated with non-IMiD-based regimens remains poorly understood. We conducted a post hoc analysis of the ALCYONE and LYRA trials to further examine this question. Methods: This retrospective study, carried out under the Yale University Open Data Access (YODA) Project #2024-0032 in collaboration with JANSSEN RESEARCH & DEVELOPMENT, L.L.C., looked at the ALCYONE trial where bortezomib, melphalan, and prednisone (VMP) ) (n=356) +/- daratumumab (DVMP) (n=350) were given in TIE NDMM, and the LYRA trial where daratumumab, cyclophosphamide, bortezomib, and dexamethasone (DVCd) were given in NDMM (N=86) or relapsed MM (N=14). TE, including venous and arterial events (V/ATE), were examined with VTE events including deep vein thrombosis, pulmonary embolism, and superficial thrombophlebitis. ATE included cerebrovascular accidents defined as hemorrhagic, ischemic, or vertebrobasilar strokes. The incidence and median time to event (mTTE) of V/ATE were calculated. Results: In the LYRA trial, 21% of all pts received thromboprophylaxis (tpx). Despite this, VTE occurred in 7% of pts. The mTTE was 3.8 (range 0.7-15.7) months (mos). In the ALCYONE trial (N=706), 40% of pts received tpx. All types of TE occurred in only 1.9% of pts. The mTTE was 5.1 (range 0.2-35.4) mos. In the DVMP cohort, all grade TE occurred in 2% of pts (VTE = 0.9%; ATE= 1.1%), while the TE rate in the VMP cohort was 1.9% (VTE = 1.7%; ATE 0.3%). The overall mTTE in the D-VMP and VMP arms were 14.5 (range 0.6-35.4) and 0.9 (range 0.2-6.7) mos, respectively. Analysis regarding specific tpx use and rates of TE based on tpx regimen are ongoing. Conclusions: In contrast to TE rates with IMiD containing regimens, and despite low utilization of tpx in this NDMM-predominant cohort from LYRA/ALCYONE, we observed a lower rate of TE in pts treated with non-IMiD containing regimens. Further research is needed to better guide tpx decision in pts with NDMM receiving non-IMiD containing regimens, particularly in those receiving DVCd. Study LYRA ALCYONE Treatment DCVd DVMP VMP TE 7% 2% 1.97% VTE 7% 0.86% 1.69% ATE 0% 1.14% 0.28% TE mTTE mos(range) 3.8(0.7-15.7) 14.4(0.6 -35.4) 0.9 (0.2-6.7) VTE - mTTE mos (range) 3.8(0.7-15.7) 5.9 (0.6-7.2) 1.8 (0.2-6.7) ATE - mTTE mos (range) - 23.6(14.4-35.4) 0.5(0.5-0.5)