Dose Adjustment of Selinexor Boosts Survival, Response Rates, and QOL in MM


The BOSTON study delivered promising findings among patients with multiple myeloma treated with selinexor, bortezomib, and dexamethasone vs bortezomib and dexamethasone.

Multiple Myeloma: © David A Litman -

Multiple Myeloma: © David A Litman -

The BOSTON trial (NCT03110562) evaluating selinexor (Xpovio) in patients with multiple myeloma (MM) found that adapting the starting dose based on initial adverse effects (AEs) yielded promising results, including improved efficacy, reduced AE rates, and a better quality-of-life.1

Among the 126 patients (65%) in the BOSTON study who had a selinexor dose reduction (median dose, 71.4 mg/week), the median progression-free survival (PFS) was 16.6 months (95% CI, 12.9-not evaluable [NE]) vs 9.2 months (95% CI, 6.8-15.5) for those who did not have a dose reduction. The overall response rates (ORR) for those who had a dose reduction vs those who did not were 81.7% (95% CI, 73.9%-88.1%) vs 66.7% (95% CI, 54.3%-77.6%), with very good partial response rates of 51.6% (95% CI, 42.5%-60.6%) compared with 31.9% (95% CI, 21.2%-44.2%).

Further, the median duration of response (DOR) was not reached (95% CI, 13.8-NE) among patients who had a dose reduction vs 12.0 months (95% CI, 8.3-NE) among those who did, and time to next treatment (TTNT) was 22.6 months (95% CI 14.6-NE) compared with 10.5 months (95% CI 6.3-18.2).

Sundar Jagannath, M.D., FASCO

Sundar Jagannath, MD, FASCO

"Starting with once weekly dosing of selinexor at 100 mg, dose can be adjusted for adverse events to improve tolerance. A starting dose of 100 mg once weekly, followed by reductions to 80 mg once weekly, 60 mg once weekly, and 40 mg once weekly. The most common adverse events of any grade were thrombocytopenia, nausea, and fatigue. These were lower after dose reduction of selinexor compared to the rates on or before dose reduction for thrombocytopenia (62.5% vs 47.6%), nausea (31.6% vs 7.3%), fatigue (28.1% vs 9.9%), decreased appetite (21.5% vs 6.4%), anemia (17.9% vs 10.3%), and diarrhea (12.9% vs 5.2%)," Sundar Jagannath, MD, FASCO, director of the Center of Excellence for Multiple Myeloma and professor of medicine at The Tisch Cancer Institute, told Targeted OncologyTM.

"Appropriate dose reductions of the 100 mg selinexor starting dose in the BOSTON study were associated with potentially longer progression-free survival, duration of response, time to next anti-myeloma treatment, reduced adverse event rates and improved quality-of-life," added Jagannath.

Selinexor has received 2 approvals from the FDA in MM based on findings from the STORM study (NCT02336815), as well as the phase 3 BOSTON study.

BOSTON was a randomized, phase 3 study which compared the efficacy and safety of once-weekly oral selinexor given at a dose of 100 mg in combination with once-weekly subcutaneous bortezomib (Velcade) and low-dose dexamethasone (XVd) with standard twice-weekly bortezomib and low-dose dexamethasone (Vd).1,2

The study evaluated efficacy, safety, and quality-of-life of the combination in 195 patients with relapsed/refractory MM, and findings were compared between patients with dose reductions and those without.1 The primary end point was PFS, and secondary end points included ORR, OS, DOR, and TTNT.

Of the 195 patients enrolled in the BOSTON study and treated with XVd, 126 (65%) had selinexor dose reduction. The median age across arms was 66.0 years, with similar age ranges observed between arms. Among patients who had a selinexor dose reduction and those who did not, 67 (53.2%) and 48 (69.6%) were male, 74 (58.7%) and 43 (62.3%) had a revised international staging system score at baseline of II, and 93 (73.8%) and 55 (79.7%) had received a prior proteasome inhibitor. The median number of prior therapies received in both arms was 1 (range, 1-3).

The median selinexor dose intensity over the course of therapy was 71.4 mg a week (range, 29.7-101.4 mg/week) in the dose-reduction group vs 100 mg a week (range, 33.3-136.7 mg/week) in the group that did not have a dose reduction. The median time to dose reduction was 68 days (range, 8-561 days), and for patients with a dose reduction, the median duration of study treatment was 34.5 weeks (range 3-120 weeks) vs 20.0 weeks (range 1-118 weeks) for those who did not.

Additional findings showed that the mean best change from baseline on the EORTC QLQ-C30 Global Health Status/QoL scale was 10.0 ± 20.5 (95% CI, 6.3-13.7) in the selinexor dose reduction group compared with 4.0 ± 20.9 (95% CI, −1.4-9.3) in the group without dose reductions. Fifty-four of 121 patients in the dose reduction group (44.6%; 95% CI, 35.6%-53.9%) had an increase of 10 points or greater from baseline compared with 20 of 61 patients (32.8%; 95% CI, 21.3%-46.0%) who did not have dose reductions.

"Dose adjustment should be guided by adverse effects such as thrombocytopenia, nausea, fatigue, loss of appetite, anemia and diarrhea. Responding patients would be able to stay on the drug longer with dose adjustments without loss of disease control," said Jagannath.

Looking at safety, the most commonly reported treatment-emergent AEs of any grade in the dose-reduction group vs no dose-reduction group included thrombocytopenia (69.8% vs 42.0%), nausea (55.6% vs 40.6%), fatigue (49.2% vs 29.0%), decreased appetite (41.3% vs 24.6%), diarrhea (38.9% vss 20.3%), peripheral neuropathy (35.7% v 26.1%), anemia (39.7% vs 30.4%), and vomiting (23.8% vs 14.5%). Investigators also looked at duration-adjusted AE rates that were lower following reductions of selinexor doses. These included thrombocytopenia (62.5% before vs 47.6% after), nausea (31.6% vs 7.3%), fatigue (28.1% vs 9.9%), decreased appetite (21.5% vs 6.4%), anemia (17.9% vs 10.3%), and diarrhea (12.9% vs 5.2%).

"Selinexor can be easily combined with other drugs to relapsed and/or refractory myeloma. Therefore, its continued use and further studies in combination with T-cell redirection therapies and CelMoDS are warranted," added Jagannath.

  1. Jagannath S, Delimpasi S, Grosicki S, et al. Association of Selinexor Dose Reductions With Clinical Outcomes in the BOSTON Study. Clin Lymphoma Myeloma Leuk. 2023;23(12):917-923.e3. doi:10.1016/j.clml.2023.08.018
  2. Bortezomib, selinexor, and dexamethasone in patients with multiple myeloma (BOSTON). Updated January 26, 2023. Accessed January 15, 2024.
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