P-180: Daratumumab (DARA) Plus Lenalidomide, Bortezomib, and Dexamethasone (RVd) in newly diagnosed Multiple Myeloma (NDMM): analysis of vascular thrombotic events (VTEs) in the GRIFFIN study

Abstract

<h3>Background</h3> DARA is approved across lines of therapy for multiple myeloma (MM). The phase 2 GRIFFIN study (NCT02874742) investigated DARA+RVd (D-RVd) in transplant-eligible NDMM; at the primary analysis, D-RVd improved efficacy, and safety was consistent with prior reports for DARA and RVd. We conducted a post-hoc analysis of GRIFFIN to evaluate anti-thrombosis prophylaxis use, in concordance with IMWG guidelines, and the incidence of VTEs, given a historical risk of VTEs with lenalidomide plus dexamethasone occurring in 10-25% of MM patients (pts). <h3>Methods</h3> Pts with NDMM eligible for autologous stem cell transplant (ASCT) were randomized 1:1 to receive 4 cycles of D-RVd/RVd induction, high-dose therapy, ASCT, 2 cycles of D-RVd/RVd consolidation, and maintenance with DARA-R/R for 24 months. During induction and consolidation (21-day cycles), pts received R (25 mg PO on Days 1-14); V (1.3 mg/m2 SC on Days 1, 4, 8, 11); and d (40 mg QW). DARA (16 mg/kg IV) was given on Days 1, 8, 15 of Cycles 1-4 and Day 1 of Cycles 5-6. During maintenance (Cycles 7-32; 28-day cycles), pts received R (10 mg PO on Days 1-21; if tolerated, 15 mg in Cycles 10+)±DARA (16 mg/kg IV Q8W or Q4W per protocol amendment 2). VTE prophylaxis was recommended for all pts (aspirin, ≥162 mg) with alternative prophylaxis for pts at increased VTE risk, based on medical history. VTEs were identified through standardized MedDRA queries, and treatment group comparisons were by descriptive analyses. <h3>Results</h3> VTEs occurred in 10% (10/99) of D-RVd pts and 15% (15/102) of RVd pts. Grade 3/4 VTEs occurred in 4% of D-RVd pts and 6% of RVd pts, with grade 3 pulmonary embolism in 1% of D-RVd pts and 4% of RVd pts. The median (range) time to VTE was 379 (6-810) and 232 (21-511) days in the D-RVd and RVd groups, respectively. Anti-thrombosis prophylaxis use was reported in 83% of D-RVd pts and 83% of RVd pts, including heparin derivates in 14% and 19% of pts, respectively (majority of pts on LMWH). Among pts who developed a VTE, 80% (8/10) of D-RVd pts and 93% (14/15) of RVd pts received anti-thrombosis medication, including LMWH in 30% and 27% of pts, respectively. However, only 60% (6/10) of D-RVd pts and 67% (10/15) of RVd pts were on anti-thrombosis prophylaxis at the time of the VTE, including aspirin in 40% and 60% of pts and LMWH in 10% and 7% of pts, respectively. One D-RVd pt received DOAC (rivaroxaban). Bone marrow involvement ≥60% plasma cells was seen in 50% of D-RVd pts and 60% of RVd pts developing VTEs, compared with 43% of all D-RVd pts and 41% of all RVd pts. <h3>Conclusion</h3> In this descriptive analysis, the use of daratumumab did not increase the VTE rate, and the median time to VTE was longer for D-RVd. Although no formal conclusion can be drawn, these observations indicate additional and larger investigations may be warranted to understand optimal VTE prophylaxis in NDMM pts, as current data show VTE prophylactic therapy adherence may be suboptimal.