PF638 VENOUS AND ARTERIAL THROMBOTIC EVENTS IN MYELOMA PATIENTS TREATED WITH IXAZOMIB, LENALIDOMIDE AND DEXAMETHASONE (IRD) OR LENALIDOMIDE AND DEXAMETHASONE (RD)

Abstract

Background: Patients with multiple myeloma (MM) are at increased risk of venous thromboembolism (VTE). Immunomodulatory agents (IMiDs) are known to contribute to this increased VTE risk. Less is known about the risk of arterial thrombosis. Combining proteasome inhibitors (PI) or monoclonal antibodies to IMiDs improves clinical outcomes and is now a standard of care. Addition of the oral PI (Ixazomib) to Lenalidomide Dexamethasone (RD) significantly improves progression-free survival in patients with relapsed / refractory MM (RRMM), with no significant difference in VTE and arterial events with addition of Ixazomib to RD. Aims: To compare the incidence of VTE and arterial events in patients with RRMM treated with RD and IRD, with reference to previous VTE history, cardiovascular (CV) risk factors and use of thromboprophylaxis (TP). Methods: A retrospective review of patient records noting prior venous thrombosis and arterial risk factors in patients treated with RD or IRD. To avoid bias in patient selection, we reviewed RRMM patients treated with RD alone (July 2014 to February 2016) or after we routinely used Ixazomib with RD (IRD, February 2016 to July 2018). VTE and arterial events whilst receiving RD or IRD were noted. Results: Each group consisted of 88 patients (176 in total). Baseline patient characteristics were: median age 65 years in both groups (Range: 32–85 for IRD, 30–88 for RD); 54% male in both groups; median number of prior lines of therapy was 3 (range 1–5); median number cycles delivered 7 (range 1–32, IRD) and 7.5 (range 1–48, RD); 8 (9%) patients were still on treatment in the RD and 35 (40%) in IRD patients at the time of data collection. Prior VTEs were higher in the IRD group; 13 (15%) patients, compared to the RD group 8 (9%) patients. Potential arterial risk factors were higher in the RD group; 31 (35%) patients, compared to the IRD group, 20 (23%) patients. The commonest arterial risk factor was hypertension; 16 (52% of those with CV risk factors) on RD and 11 (55% of those with CV risk factors) on IRD patients. Four (5%) patients in each cohort had a prior CVA/TIA. Obesity (Body Mass Index ≥ 30) was higher in the RD group: 26 (30%) patients compared to the IRD group 18 (21%) patients. Aspirin VTE TP was given in 60 (62%) and 68 (77%) IRD and RD patients respectively. More DOAC prescriptions were noted in the IRD group (12 patients, 13%), vs RD (2 patients, 2%). In those patients receiving IRD; 5 (5.7%) VTEs (3 PE, 1 venous sinus thrombosis, 1 DVT). Four VTEs occurred on aspirin, the other on rivaroxaban TP. For RD there were 3 (3.4%) VTEs (1 PE and 2 DVT), all on aspirin TP. Two patients (2.3%) had arterial events whilst receiving IRD (TIA after 6 months with no risk factors; stroke after 3 months, hypertension only risk factor), 1 RD patient (1.1%) developed a stroke 11 months after starting RD (known hypertensive and diabetic). Summary/Conclusion: VTEs occur at a lower rate than reported; between 3 and 6%, compared to 8–11% in the Touramaline MM1 trial, however we note VTEs of potential clinical concern (PE or venous sinus thrombosis), 4 events in the IRD and 1 in the RD group. VTEs still occurred despite thromboprophylaxis. The IRD group had more previous VTEs, but a lower obesity rate. This requires further exploration. Arterial events occur at a similar rate to that reported (1–2%), and occur early in treatment, despite aspirin TP and in the absence of other risk factors. Strategies to prevent this are urgently needed.