Background: Len maintenance post ASCT is standard of care for patients (pts) with NDMM. Deep responses (CR or better) post ASCT correlates with better progression free survival (PFS). In a meta-analysis of len maintenance post ASCT (McCarthy PL et al. J Clin Oncol. 2017), only 10.7% of pts achieve CR post ASCT, and 72% of pts who discontinued len maintenance did so because of progressive disease (PD). Selinexor is a selective inhibitor of nuclear export that blocks exportin 1, thus retaining tumour suppressor proteins within the nucleus while blocking proto-oncoprotein translation. It is approved in combination with bortezomib and dexamethasone (dex) for pts with MM who have had at least 1 prior line of treatment, or with dex for pts with penta-refractory MM by the FDA. The oral bioavailability and weekly schedule of selinexor makes it suitable in combination with len for maintenance therapy. Given the encouraging activity (ORR 92%) and tolerability of selinexor, len and dex from the phase 1b/2 STOMP study, we hypothesise that combination low-dose selinexor and len (XR) will be well tolerated and effective, increasing CR and MRD negativity rate post ASCT, thus prolonging PFS compared to len. Methods: ALLG MM23 SeaLAND, is an ongoing randomised, multi-centre, phase 3 trial. Eligible pts ( > 17 years of age) have measurable disease, have undergone 3-6 cycles (C) of induction containing a proteasome inhibitor (PI) and/or immunomodulatory drug and recovered post melphalan-conditioned ASCT with adequate haematopoiesis, renal and liver function, and with ECOG performance status. Registration occurs prior to ASCT with screening between 75 to 115 days post ASCT. The study includes a lead-in safety phase of 20 patients with XR: Len 10mg daily days 1 to 21 and Selinexor 40mg weekly in a 28-day cycle. If well tolerated, Selinexor escalates to 60mg po weekly from C2 and Len to 15mg po daily from C4. Two safety reviews will occur after the 10^th and 20^th patients completes C2, respectively. Upon meeting safety criteria, a sample size of 290 pts will be randomised 1:1 to XR or lenalidomide (R). Therapy will continue until PD. The primary endpoint is PFS at 3 years post randomisation. Secondary endpoints include ORR and MRD-negativity rate (International Myeloma Working Group Response Criteria), PFS on next treatment line (PFS2), OS, safety and tolerability, quality of life, and cost effectiveness. Main analysis occurs after 232 patients complete 3-years of follow-up. Exploratory objective is to correlate immunological and molecular profiles to treatment response and resistance. ALLG MM23 SeaLAND is a multisite bi-national investigator-initiated trial lead by Australia and New Zealand’s national cooperative group, the Australasian Leukaemia & Lymphoma Group. Clinical trial registration: ACTRN12620000291987p. Clinical trial information: 12620000291987.