Thrombosis in multiple myeloma: Risk estimation by induction regimen and association with overall survival

Abstract

Lenalidomide‐containing (R) triplet and quadruplet regimens are the standard of care for multiple myeloma (MM) and have been shown to increase the risk of thrombosis. The association between thromboembolism (TE) and survival in the novel multidrug era is not yet delineated. In this study, we evaluated the incidence of TE during the first year of MM diagnosis, its association with the type of induction regimen, and its impact on overall survival. We studied 672 newly diagnosed MM (NDMM) patients who received a triplet or quadruplet lenalidomide‐based induction at the Mayo Clinic, Rochester. TE was diagnosed in 83 patients (12.4%). Of these, 56 (8.3%) had a deep venous thrombosis (DVT), 23 (3.4%) had a pulmonary embolism (PE) with or without the DVT, and 4 (0.6%) patients had a stroke. Carfilzomib‐Rd (KRd) had the highest risk of TE (21.1%, 18/85), followed by quadruplets (11.1%, 5/45), bortezomib‐Rd (9.6%, 51/531), and 0/11 (0%), treated with other lenalidomide‐containing regimens. The difference in TE risk between KRd and the other regimens was statistically significant (OR = 2.6, p < .01). Nine patients developed a TE before being exposed to any treatment. Survival was significantly lower among patients that developed a TE (66 vs. 133 months, p < .01). The association of TE with reduced survival demonstrated in univariate analysis (HR = 2.2, 95% CI = 1.6–3.3) was maintained in the multivariable analysis adjusted for high‐risk interphase fluorescence in situ hybridization (FISH), sex, age, receipt of an upfront transplant, the response at induction, and the International Staging System (ISS) (HR = 2.61, CI = 1.74–3.9). We conclude that TE is an important aspect of MM management, and effective management is especially relevant in the novel treatment era.

Thromboembolic risk of carfilzomib or bortezomib in combination with lenalidomide and dexamethasone for newly diagnosed multiple myeloma: A comparative systematic review and meta‐analysis

“…The distinctive thrombogenicity of two induction regimens commonly used for NDMM — carfilzomib/Rd (KRd) and bortezomib/Rd (VRd) — has been a matter of debate, with the current literature revealing divergent findings. For instance, Piedra et al demonstrated an increased VTE incidence among KRd‐treated patients in comparison with VRd‐treated patients, whereas Gaballa et al found no significant difference in thrombosis rates between these triplets 11–16 . In view of the foregoing, we decided to perform a systematic review and meta‐analysis aimed at comparing the thromboembolic risk associated with KRD versus VRD as frontline therapy for NDMM.…”

“…For instance, Piedra et al demonstrated an increased VTE incidence among KRd-treated patients in comparison with VRd-treated patients, whereas Gaballa et al found no significant difference in thrombosis rates between these triplets. [11][12][13][14][15][16] In view of the foregoing, we decided to perform a systematic review and meta-analysis aimed at comparing the thromboembolic risk associated with KRD versus VRD as frontline therapy for NDMM.…”

Bleeding risk from anticoagulant thromboprophylaxis in patients with multiple myeloma: a MarketScan analysis

“…The combination of patient- (age and immobility) [ 2 ] and disease-specific (hypercoagulability, plasma viscosity, and endothelial inflammation) [ 3 ] risk factors and prothrombotic therapies (high dose dexamethasone and immunomodulatory drugs [IMiDs]) [ 4 ] increases thrombosis risk in a population perceived to be at high risk for bleeding. In the current era of novel triplet and quadruplet combinations and improved survival in MM, VTE still occurs in over 10% of patients, particularly in the first 6 months of treatment, and is associated with inferior survival [ 5 ].…”