Thromboembolism in transplant-ineligible multiple myeloma patients on triplet/quadruplet therapy: a post-hoc analysis of BENEFIT.

Background: Venous thromboembolism event (VTE) remains a major concern for patients with newly diagnosed multiple myeloma (nMM) undergoing therapy.

Methods: This post hoc analysis of the randomized phase 3 BENEFIT trial (NCT04751877) evaluated the incidence and risk factors for VTE in 257 patients aged 65-79 years with transplant-ineligible (TI) nMM who received isatuximab/ bortezomib/lenalidomide/dexamethasone or isatuximab/lenalidomide/dexamethasone.

Results: In the whole cohort, the 6-month cumulative incidence of VTE was 4.8% (95% CI, 2.7-8.1%); 0.8% (95% CI, 0.1-5.6%) in patients receiving low-dose direct oral anticoagulants (DOACs) compared to 5.6% (95% CI, 1. 9-16.7%) in those who received prophylactic-dose heparin and 9.8% (95% CI, 3.9-24.75 in patients receiving aspirin. Only one VTE occurred beyond the 6-month period. The most frequently used thromboprophylaxis agents were DOACs (n=127, 55.2%), low molecular weight heparins (n=54, 23.5%), and aspirin (n=40, 17.4%). We noted that one-third of patients who experienced VTE had not received thromboprophylaxis. Among the different thromboprophylaxis regimens used, only a low-dose DOAC was associated with a significant reduction in the risk of VTE. In multivariate analysis, proteinuria ≥ 0.44g/L (HR 5.8; 95% CI, 1.7-26.8) and M-protein level ≥ 22g/L (HR 4.9; 95% CI, 1.3-31.9), were significantly associated with an increased risk of VTE while low-dose DOAC was associated with a decreased risk for VTE (HR 0.13; 95 %CI, 0.007-0.67).

Conclusions: In summary, the cumulative incidence of VTE remains high in patients with TI nMM. DOACs could be the most effective option for preventing VTE.