ASH 2025 | The SeaLAND study: lenalidomide ± selinexor as maintenance post-autoSCT in newly diagnosed myeloma

Selinexor is a selective exportin-1 inhibitor that is approved in relapsed multiple myeloma in combination with bortezomib and dexamethasone. We investigated whether low-dose selinexor in combination with lenalidomide was superior to lenalidomide alone as maintenance therapy following autologous stem cell transplant in newly diagnosed multiple myeloma. This is the primary analysis of the randomized label phase 3 SeaLAND study run by the ALLG. 

Eligible patients had to have had three to six cycles of bortezomib or lenalidomide-based induction and previously received an autologous stem cell transplant. They were screened and randomized from day 75 to 115 post-transplant. After a safety run-in, a selinexor dose of 40 milligrams was deemed safe, and patients were randomized one-to-one to receive either selinexor with lenalidomide or lenalidomide alone. Patients were given ondansetron and olanzapine as therapy for nausea associated with selinexor. 

We enrolled 149 patients in this study, with 65 randomized to lenalidomide and 84 randomized to selinexor and lenalidomide. The study had originally planned to enroll 290 patients; however, after a futility analysis was performed that indicated no statistically significant difference in progression-free survival between the two, the trial was halted. The median age of our cohort was 62 years. There was around 25% of individuals having high-risk cytogenetic abnormalities. 

In terms of their best response, the rate of complete response was slightly higher in the selinexor and lenalidomide arm at 64% compared to lenalidomide alone at 51%, with a p-value of 0.056; however, this did not reach statistical significance. The overall rate of MRD negativity done by next-generation cytometry at any time point was 18% for patients receiving lenalidomide alone, and 17% for the combination arm. Amongst patients with deletion 17p, there was no significant difference in the rates of MRD negativity between the two arms. And at a median follow-up of 30 months, there was no significant difference in progression-free survival between the treatment groups with a hazard ratio of 1.14 and a p-value of 0.69. 30-month progression-free survival rates were 67% for lenalidomide alone and 71% for combination lenalidomide and selinexor. 

Importantly, in terms of tolerability, we saw that for patients receiving the combination approach, the mean number of selinexor-containing cycles was 9, despite the mean number of total cycles being 15. Importantly, as well, the relative dose intensity of lenalidomide was significantly lower in the combination arm at 68% compared to 81% for those receiving lenalidomide alone. As one might expect, there were more grade three adverse events in the selinexor-based arm, including higher rates of infection, gastrointestinal disorders, fatigue, and cytopenias. Despite the higher rates of adverse events, quality of life questionnaire scores were comparable between the two arms throughout the study period. 

So this randomized phase three trial shows that the addition of low-dose selinexor to lenalidomide maintenance following autologous stem cell transplant did not improve progression-free survival compared to lenalidomide alone in newly diagnosed multiple myeloma. Although we did observe a higher complete response rate with the combination arm, this came at the cost of increased toxicity with more infections, cytopenias, and gastrointestinal adverse events. Although this is a negative study, these results are important and suggest that, due to toxicity or the low disease burden that exists after stem cell transplant, selinexor may be more suited to induction rather than maintenance therapy. And ongoing follow-up will clarify whether there is any role for this doublet for patients with high-risk cytogenetics.

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