SeaLAND trial (ALLG MM23)

Background

Phase III, randomized, open-label trial (ALLG MM23, SeaLAND), Australasia. 142 patients with transplant-eligible newly diagnosed multiple myeloma after autologous SCT. Selinexor = oral XPO1 inhibitor. Tested whether low-dose weekly selinexor deepens responses and prolongs PFS on lenalidomide maintenance. Closed early after futility analysis.

Results

Interventions and follow up: Arm A: Selinexor 40 mg PO weekly + lenalidomide (n=78)
Arm B: Lenalidomide alone (n=64)
Primary endpoint: PFS
mFollow up: 24mo
Results: PFS: HR 1.22, 95% CI 0.62–2.41, P=.56; 24-mo PFS 70% vs 73%
≥CR (best response): 67% vs 53%, P=.09
High-risk subgroup: no benefit observed
Lenalidomide relative dose intensity: 68% vs 81%, P=.002; selinexor RDI 55%

Adverse events

Grade ≥3 (any): 85% vs 45%, P<.001
Infections G≥3: 19% vs 6%
GI G≥3: 14% vs 3%

Conclusions

Adding low-dose selinexor to lenalidomide maintenance after ASCT did not improve PFS or significantly increase CR rate, and substantially increased toxicity while compromising lenalidomide dose intensity. Selinexor-lenalidomide maintenance is not recommended.

Key Limitations

Small (N=142) and closed early for futility; underpowered for modest effects and OS. Short follow-up (24mo) for a maintenance endpoint. Open-label. Unbalanced arms (78 vs 64). Reduced lenalidomide dose intensity in the combination arm may have offset any selinexor effect. Pre-dates widespread quadruplet induction and anti-CD38 maintenance.

Clinical Context

Lenalidomide maintenance post-ASCT remains standard (NCCN/ESMO); intensified maintenance with anti-CD38 (e.g., daratumumab-lenalidomide, per PERSEUS/AURIGA) is the evidence-based escalation, particularly for high-risk or MRD+ disease. Selinexor is FDA-approved only in relapsed/refractory MM (with dexamethasone ± bortezomib); SeaLAND provides no support for maintenance use.

References