Myeloma Therapy Driven by Measurable Residual Disease: De-Escalating Treatment Intensity

Standard frontline myeloma therapy includes autologous stem cell transplant (ASCT) consolidation for medically fit patients. To test whether those who achieve deep response to induction therapy can forego ASCT, investigators conducted a partially industry-sponsored phase 3 trial in patients aged 65 or younger with newly diagnosed myeloma who received 6 cycles of the quadruplet induction regimen Isa-KRd (isatuximab, carfilzomib, lenalidomide, and dexamethasone). Patients who achieved negativity of measurable residual disease (MRD) at <10^-5 sensitivity (determined with next-generation sequencing) were randomized to ASCT plus 2 cycles of Isa-KRd versus 6 additional cycles of Isa-KRd. Patients who were MRD-positive at 10^-5 sensitivity proceeded to tandem ASCT versus single ASCT plus Isa-KRd for 2 cycles.

Among the 485 patients who were MRD-negative after induction therapy, ASCT conferred no benefit over continuing Isa-KRd alone in achieving deeper response (MRD-negative at <10^-6 sensitivity; 86% and 84%, respectively [the primary endpoint]). Of the 233 patients who remained MRD-positive after induction therapy, 32% of the tandem-ASCT group became MRD-negative before maintenance therapy compared with 40% of the single-ASCT group, a nonsignificant difference.