Risk of Venous Thromboembolism in Multiple Myeloma Patients Undergoing Autologous Hematopoietic Cell Transplant

Introduction: Venous thromboembolism (VTE) is a common complication that could affect multiple myeloma (MM) patients. Previous studies suggested the incidence of VTE in MM patients not on VTE prophylaxis to be as high as 10.7% in the peri-transplant period. Usage of antiplatelet or anticoagulant VTE prophylaxis is often a challenging clinical decision especially in patients with profound thrombocytopenia. Here, we aimed to explore the incidence and risk factors for VTE in MM patients undergoing AHCT.

Methods: The electronic medical records of all MM patients who underwent AHCT at Cleveland Clinic between January 1^st, 2011 and January 15^th, 2021 were reviewed. We evaluated the incidence and type of venous thrombosis occurring in the immediate peri-transplant period, defined as extending from the start of stem cell apheresis up to 30 days post-AHCT. Baseline patient, demographic, disease, and transplant factors were evaluated to analyze risk factors for VTE occurrence within the studied period. Statistical Package for Social Sciences (SPSS) was used for statistical analysis.

Results: A total of 493 patients with available records were included in our study. The median age was 61.4 years (range 33.1-77.7 years) at the time of AHCT with a male preponderance of 59%. Symptomatic VTE was recorded in 23 events involving 17 patients (3.5%) within the defined peri-transplant period, of which 34.8% of the events occurred between the start of stem cell apheresis and the date of transplant (i.e. day 0). Around 34.8% of VTE events, involving 6 (35.3%), patients occurred during hospitalization for the transplant procedure. All VTEs were non-catheter related, and most were lower extremity deep venous thromboses (DVT) (52.2%), followed by pulmonary emboli (17.4%), DVT of upper extremities (13%), internal jugular thromboses (13%) and superficial vein thrombosis (4.4%). Of the 17 VTE patients, 41% had history of previous VTE prior to the defined peri-transplant period, 88.2% were recently on immunomodulatory drugs (IMiD), 76.5% were on either antiplatelet (41.2%) or anticoagulant (53%) therapy or both (17.7%), while 23.5% were on none. Most of the VTE patients were never smokers (70.6%), while the rest (29.4%) were ex-smokers. Of note, 35.3% of VTE patients had thrombocytopenia (Platelets <150 x10⁹/L) but median platelet count of 184 x10⁹/L.

Patients who developed VTE were of similar age (median 62.1 vs 61.4 years, P=0.9) but had a higher female preponderance (64.7 vs 40.1%, P=0.04) compared to those who did not. In addition, they had similar albumin levels at diagnosis (75 vs 71.7% ≥ 3.5 g/dL, P=0.8), similar cytogenetic risk categorization (high risk in 35.3 vs 25.8%, P=0.4), ISS stages (P=0.5), disease remission status prior to AHCT (P=0.3), mobilization regimens (G-CSF + Plerixafor in 88.2 vs 88.2%, P=0.1), and recent IMiD use (88.2 vs76.7, P=0.26) (Table 1). However, VTE patients were more likely to have IgG MM (70.6 vs 62%, P=0.06), Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) ≥1 (100 vs 81.1%, P=0.05), infection at AHCT (12.5 vs 3.2%, P=0.05), longer length of AHCT hospital stay (median 17 vs 14.9 days, P<0.0001), and had higher prevalence of prior history of VTE (41.2 vs 11.6%, P<0.0001) (Table 1). With regards to prophylaxis therapy, VTE patients were less likely to be on antiplatelets (41.2 vs 65.6%, P=0.039), were on similar prophylactic anticoagulation (11.8 vs 19.5%, P=0.42), but were more likely to be on therapeutic anticoagulation (41 vs 14%, P=0.002) compared to non-VTE pts, suggesting a higher impact of a history of prior VTE than therapeutic anticoagulation on recurrence of VTE during the studied time period. Among patients with no history of previous VTE, non-VTE patients were more likely to be on either antiplatelet or prophylactic anticoagulation (82.6 vs 50%, P=0.02). Interestingly, no difference was seen in the incidence of VTE with antiplatelet vs prophylactic anticoagulation in patients without history of previous VTE (1.86 vs 0%, P=0.9). Moreover, among those with a history of previous VTE, the addition of antiplatelets to therapeutic anticoagulation did not significantly lower the risk of VTE recurrence in the studied time period (9 vs 16%, P=0.9).

Conclusion: The use of VTE prophylaxis among MM patients undergoing AHCT may lower its incidence. The main risk factors for VTE are female sex, history of previous VTE, infections at AHCT, HCT-CI ≥1, and longer hospital stay.