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)+. Median follow up was 45.8 months. MRD negativity (10-5) for t(11;14)+ vs. t(11;14)- was 9% vs. 31% (P<0.001), 36% vs. 59% (P=0.004), and 53% vs. 75% (P=0.004) at post-induction, post-ASCT and any time on treatment, respectively. The rates of sustained MRD negativity (S-MRD)<10-5 were 38% vs. 46% (P=0.43). Median time to MRD<10-5 was 13.6 vs 7.7 months (P=0.002) for t(11;14)+ vs. t(11;14)-, respectively. PFS was superior for t(11;14)+ patients (P=0.012), with 4-year PFS rates of 90% vs. 72%. In multivariable analysis, S-MRD<10-5 (HR 0.41, P=0.002) and t(11;14)+ (HR 0.36, P=0. 048) were associated with reduced risk of progression or death, with no progression seen in t(11;14)+ patients who achieved S-MRD<10-5. In the setting of QUAD/ASCT therapy and MRD-adapted post ASCT management, t(11;14)+ NDMM in associated with improved prognosis despite slow conversion to MRD negativity.