Selinexor Dose Reduction Improves The QoL Of RRMM Patients

The exploratory, post-hoc analysis demonstrated that lowering the dosage of selinexor was linked to enhanced quality of life (QoL) among patients (pts) dealing with relapsed/refractory multiple myeloma (RRMM). These results and the earlier findings indicate that decreasing the selinexor dosage improves tolerability and effectiveness in the BOSTON phase 3 trial. It emphasized that reducing the dose is important for maximizing the treatment approach for RRMM.

The FDA has approved the use of the oral XPO1 inhibitor selinexor in treating RRMM along with dexamethasone (Xd) or bortezomib and dexamethasone (XVd) in adults who have obtained at least one prior treatment. The recommended initial dose of selinexor in the XVd regimen is 100mg weekly. However, the BOSTON study showed that the median dose administered was 80mg per week (with a range of 30-137). Earlier analysis revealed that pts who encountered selinexor dose reduction experienced fewer adverse events and an enhanced progression-free survival rate.

During the BOSTON trial, pts with multiple myeloma (MM) were randomly assigned into two groups. The first group received selinexor once a week (100mg), subcutaneous bortezomib once a week (1.3mg/m²), and dexamethasone twice a week (20mg) (n=195). The second group followed the standard regimen of subcutaneous V (bortezomib) twice a week and dexamethasone. The patients’ QoL was evaluated at the baseline and on day-1 of each treatment cycle using the EORTC QLQ-C30 assessment tool, and a meaningful change was defined as a 10-point difference.

A totol of 126 pts underwent a reduction in selinexor dosage, with a median weekly selinexor dose of 71.3mg, while 69 did not (median=100mg/week; median age=66, median prior therapies=1 in both groups). Analyzing the EORTC QLQ-C30 Global Health Status/QoL scores, the selinexor dose reduction group displayed a mean of 10.0 points (STD=20.5) from baseline, as opposed to the non-reduction group, which showed a 4.0-point improvement (STD=20.9). 54 pts (45%) achieved an increase of 10 points or more from baseline. In contrast, the non-reduction group had 20 pts (33%) reaching this threshold. Following the first selinexor dose reduction, a mean of 4 points (STD=18.4) was observed during the subsequent assessment, increasing to 12.8 points (STD=20.7) for the best post-reduction score. Most pts in the dose reduction group (n=66, [72.5%]) attained their best post-baseline scores after the initial dose reduction, including cases where scores were tied for the best. The group in which the dosage was reduced displayed enhanced efficacy and fewer adverse events.

On average, patients experienced an enhancement in their Quality of Life (QoL) following the reduction of selinexor dosage. These findings are consistent with the previous report that showed that decreasing the amount of selinexor resulted in lower rates of adverse events and improved ability to tolerate the treatment with increased treatment efficacy. The results confirmed that reducing the dose is important for optimizing the treatment spectrum for patients with RRMM.

Source: https://ons.confex.com/ons/2023/meetingapp.cgi/Paper/12515

Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT03110562

Jagannath, S., Delimpasi, S., Grosicki, S., Auner, H., Špička, I., Dimopoulos, M.