ASH 2025 | MRD trajectory and prognosis in t(11;14) multiple myeloma treated with quadruplet therapy and ASCT

So at ASH 2013, we also had a chance to present an abstract on distinct trajectories and prognosis of measurable residual disease in translocation t(11;14) multiple myeloma. The reason to look into this information is because we saw recently on the MEDAS trial, the patients with t(11;14) translocation were less likely to achieve MRD negativity post-induction therapy than other patients, including patients with cell genetic high risk, generating the concern that perhaps in the era of quadruple therapy and autologous transplant, these patients might actually have a worse prognosis. We long recognized that t(11;14) has a different biology altogether. The cells look different morphologically. They have different immunophenotypes, and their pattern of response to therapy can be somewhat distinct, as is amplified very well in the example of the BCL2 inhibitors. So we took advantage of a large data set of 310 patients, all treated with quadruple therapy, all treated with autologous transplant, and all treated with post-transplant MRD-adapted consolidation and maintenance treatment to better describe the trajectory of MRD negativity in t(11;14) versus other patients. And what we saw was indeed the rate of MRD negativity at 10 to minus 5 and 10 to minus 6 was lower in t(11;14) before transplant, remained lower, but with a substantial increment after transplant. And if you look at MRD negativity at any time, it’s still somewhat lower in the t(11;14) patients than in t(11;14) negative patients. The same applied to 10 to minus 6. Also, the timing to achieve MRD negativity was slower. It was 7.7 months in t(11;14) negative patients and was over 13 months in t(11;14) positive patients. However, we found that overall, the rate of sustained MRD negativity, so two consecutive measurements at least a year apart, was very similar between t(11;14) positive and negative patients. And overall, the prognosis of t(11;14) positive patients was superior to their t(11;14) negative counterparts. So in the era of quad and autologous transplant, despite the slow achievement of MRD negativity, patients with t(11;14) actually have a better prognosis than their counterpart. And that begs the question if MRD negativity matters at all. So we did a multivariable analysis, including cytogenetic risk, actually ISS, achievement of sustained MRD negativity, and t(11;14) status. And we showed that t(11;14) status and achievement of sustained MRD negativity are both protectors of PFS events. In other words, the best case scenario is when you have a t(11;14) and achieve MRD negativity. And none of those patients had progression despite coming off therapy due to their sustainability of their MRD response. So we think it is the disease that is just somewhat different, does not have worse prognosis, might have better. And we started to shape a profile of patients with this abnormality that actually are great candidates for treatment discontinuation because they seem to have a ridiculously low rate of progression despite no further therapy.

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