Oral Ixazomib Maintenance Following Autologous Stem Cell Transplant (asct) In Patients With Newly Diagnosed Multiple Myeloma (ndmm):
Topic: Myeloma and other monoclonal gammopathies — Clinical
Background:The double-blind TOURMALINE-MM3 study (NCT02181413) included patients (pts) with NDMM who hadachieved at least a partial response (PR) following induction therapy, high-dose melphalan conditioning, andsingle ASCT within 12 months of diagnosis (Dimopoulos, Lancet 2019). This study previously demonstrated astatistically significant and clinically meaningful improvement in its primary endpoint of progression-freesurvival (PFS) for ixazomib (ixa) maintenance vs placebo (pbo; median PFS: 26.5 vs 21.3 months; P=0.0023). Aninterim analysis showed no statistically significant difference in the key secondary endpoint of OS (Dimopoulos,ASH 2021).
Aims:To report the final OS analysis in the TOURMALINE-MM3 intent-to-treat population and pt subgroups ofinterest.
Methods:Full methods have been published previously (Dimopoulos, Lancet 2019). Eligible pts were randomized 3:2 toreceive single-agent ixa maintenance (3 mg for cycles 1–4, and if tolerated, 4 mg from cycle 5; n=395) ormatching pbo (n=261) on days 1, 8, and 15 in 28-day cycles for up to 26 cycles, or until progressive disease(PD) or unacceptable toxicity, whichever came first.
Results:At data cutoff (Sep 08, 2023), in the ixa vs pbo arms, 49% vs 58% of pts had discontinued treatment prior tocompletion of 26 cycles; 36% vs 46% of discontinuations were due to PD and 6% vs 3% due to adverse events.Median follow-up for ixa vs pbo was 94.4 vs 94.5 months, OS events had occurred in 36% vs 36% of pts, andmedian OS was not reached (NR) vs NR (hazard ratio [HR], 1.025; 95% confidence interval [CI]: 0.789–1.332;**P=0.850). There were no significant differences in median OS for ixa vs pbo among pts: with baseline high-riskcytogenetics [del(17p) and/or t(4;14) and/or t(14;16)] (64.2 vs 69.0 months; HR, 0.970; 95% CI: 0.583–1.613);with minimal residual disease (MRD) at study entry (105.0 months vs NR; HR, 0.966; 95% CI: 0.682–1.368); whowere MRD negative at study entry (NR vs NR; HR, 0.700; 95% CI: 0.414–1.184); aged <60 years (NR vs NR; HR,1.295; 95% CI: 0.862–1.944); aged between ≥60 and <75 years (105.0 vs 94.2 months; HR, 0.907; 95% CI:0.629–1.307); who received a proteasome inhibitor (PI) as part of next-line therapy (NR vs 94.2 months; HR,0.794; 95% CI: 0.523–1.206); or whose next-line therapy did not include a PI (74.9 vs 90.3 months; HR, 1.310;95% CI: 0.901–1.904). In ixa vs pbo arms, 73% vs 73% of pts received ≥1 subsequent anti-myeloma therapy,including: corticosteroids (91% vs 89%); immunomodulatory drugs (89% vs 85%); PIs (63% vs 74%); andmonoclonal antibodies (48% vs 39%). Median PFS2 (PFS on next-line therapy) for ixa vs pbo was 84.0 vs 80.4months (HR, 1.015; 95% CI: 0.795─1.298). Incidences of new primary malignancies (NPMs) in the ixa vs pboarms were 7% vs 8%; incidences of hematological NPMs were 2% vs 3%. Pt global health quality of life (QoL)score was maintained in both arms over the course of treatment.