Distinct trajectory of measurable residual disease in t(11;14) myeloma treated with quadruplet therapy

Quadruplet (QUAD) induction and autologous stem cell transplantation (ASCT) leads to high rates of measurable residual disease (MRD) negativity with improved outcomes in multiple myeloma (MM). The t(11;14) confers unique biology and different kinetics of treatment response. We analyzed MRD trajectories of patients treated with QUAD/ASCT and MRD-adapted post-ASCT management. Of the 302 patients assessed, 47 (16%) had t(11;14)+ MM. Median follow-up was 45.8 months. MRD negativity at <10-5 level (MRD <10-5) for t(11;14)+ vs t(11;14)- MM was 9% vs 31%, 36% vs 59%, and 53% vs 75% after induction, after ASCT, and any time on treatment, respectively. The rates of sustained MRD negativity <10-5 (S-MRD <10-5) were 38% vs 46%. Median time to MRD <10-5 was 13.6 vs 7.7 months for t(11;14)+ vs t(11;14)- MM, respectively. Progression-free survival (PFS) was superior for patients with t(11;14)+ MM, with 4-year PFS rates of 90% vs 72%. In multivariable analysis, S-MRD <10-5 were associated with reduced risk of progression or death, with no progression seen in those with t(11;14)+ MM who achieved S-MRD <10-5. In the setting of QUAD/ASCT therapy and MRD-adapted post-ASCT management, t(11;14)+ newly diagnosed MM is associated with improved prognosis despite slow conversion to MRD negativity.