Selinexor, Bortezomib and Dexamethasone: An Effective Salvage Regimen for Heavily Pretreated Myeloma Patients

Abstract

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.

Selinexor: Targeting a novel pathway in multiple myeloma

“…In addition to the STOMP study (Table 3) [62], selinexor‐Vd has been investigated in two studies of heavily pretreated patients with RRMM (Table 4) [77, 78]. Reflecting the efficacy seen with selinexor‐dexamethasone in this later‐relapse setting, both studies showed notable response rates, with three of the 10 patients across the studies achieving ≥VGPR.…”

“…or standard-risk cytogenetics, the benefit of selinexor-Vd versus Vd was maintained in terms of ORR (high-risk 79% vs. 58%; standard-risk 75% vs. 65%) and PFS (high-risk: median 12.9 vs. 8.6 months, HR 0.73; standard-risk: median 16.6 vs. 9.5 months, HR 0.61), albeit that there was evidence of the poor prognostic impact of high-risk cytogenetics on outcomes in both arms [63] In addition to the STOMP study (Table 3) [62], selinexor-Vd has been investigated in two studies of heavily pretreated patients with RRMM (Table 4) [77,78]. Reflecting the efficacy seen with selinexordexamethasone in this later-relapse setting, both studies showed notable response rates, with three of the 10 patients across the studies achieving ≥VGPR.…”

Selinexor and Other Selective Inhibitors of Nuclear Export (SINEs)—A Novel Approach to Target Hematologic Malignancies and Solid Tumors

“…Management algorithms suggest considering selinexor in heavily pretreated MM patients as an alternative to BCL-2 inhibitor venetoclax, immunotherapy or CAR-T cell therapies [30]. In December 2020, selinexor was approved by the FDA in combination with bortezomib and dexamethasone for patients who have undergone one prior therapy only [31].…”

“…Selinexor is a promising agent already registered for the second or further line therapy of R/R MM [31] and in the third or further line therapy of DLBCL NOS [50]. The drug has already been and is still being assessed in numerous clinical and preclinical studies.…”