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Multiple myeloma (MM) patients with triple-and penta-refractory disease have a poor survival and limited treatment options. Selinexor, in combination with bortezomib and dexamethasone, demonstrated clinical activity in the STOMP study as well as in the BOSTON study in previously treated patients with disease refractory to a proteasome inhibitor (PI). Patients and Methods: Here, we report a real-world case series of 7 heavily pretreated MM patients who had been extensively pretreated with bortezomib and had disease refractory to PIs, including carfilzomib; who were administered a starting dose of 100 mg of selinexor, 20-40 mg dexamethasone and 1.3 mg/m 2 of bortezomib, each once weekly. The majority of these patients (6 patients, 86.0%) had penta-refractory disease, with 5 patients (71.4%) having disease refractory to bortezomib and carfilzomib, and all 7 patients having pomalidomide refractory disease. The median number of prior lines of therapy was 8 (range 4-12). Results: The seven patients in this case series received selinexor for a median of 5 cycles (range 1-10). Four patients (57.1%) had a dose reduction of selinexor. Five patients (71.4%) had a response, of which 2 (29.0%) had a very good partial response (VGPR) and 3 (43.0%) had a partial response (PR). One patient (14.3%) had stable disease (SD) and 1 (14.3%) had progressive disease (PD). There were no new safety signals. Conclusion:The selinexor, bortezomib, and dexamethasone triplet combination demonstrates activity in PI-resistant MM and patients with heavily pretreated MM with refractory disease and after multiple lines of therapy.

Lenalidomide (Revlimid®) combined with intermittent dexamethasone (the RD regimen) is one of the current standards for treatment of patients with relapsed/refractory multiple myeloma (MM). However, since the disease in the majority of patients will become resistant to RD, or treatment with RD needs to be discontinued due to side effects, we evaluated the combination lenalidomide, low-dose oral cyclophosphamide, with prednisone (REP) in patients with relapsed/refractory MM previously exposed to RD. For this purpose, we performed a single centre retrospective study of the efficacy of REP in 19 patients with relapsed/refractory MM. Overall response rate (partial response or better) with REP was 68% compared with 83% with RD, but with a shorter time to response with the triplet REP. Time to progression after REP was 6 months. Overall the REP regimen was better tolerated compared to RD. We conclude that the REP regimen is an effective treatment regimen for patients with relapsed/refractory MM with good tolerance, warranting further exploration in prospective randomized trials.

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