ASH 2022 | MRD conversion rate with consolidation chemotherapy in AML

This is a trial that comes out of the University of California Hematologic Malignancies Consortium. It’s an interesting trial that kind of sets a benchmark for further trials that may look at the conversion of MRD positivity. Now, in this trial, which was again performed at multiple institutions in this consortium, patients who had received induction chemotherapy for AML were evaluated by a variety of techniques to look for evidence of minimal residual disease over a five-year period. The methods to look for measurable residual disease included flow cytometry, next-generation sequencing, realtime PCR and in-situ hybridization. Of the total population that had achieved remission, 83 met inclusion criteria with some evidence of measurable residual disease at the time of morphologic complete remission with hematopoietic recovery. Nearly half of these patients had MRD detected by multiparameter flow, but there were also nearly the same amount whose MRD was identified by next-generation sequencing.

A smaller proportion of patients had MRD detected by quantitative PCR, and some of these patients had abnormal FISH or karyotype, and there were overlap in these patients. In these 83 patients, 28 of them had MRD detected by more than one method. Consolidation therapy was not built into this retrospective trial, but most patients received dose-intensified cytarabine, either intermediate or high-dose cytarabine. And the number of cycles was also not predetermined. Some patients, three patients, received the liposomal daunorubicin-cytarabine combination. Most patients received at least one cycle, but about a little more than a quarter received two cycles. And there were some patients who received three or four cycles. A few patients also received targeted therapy with sorafenib, midostaurin, gilteritinib, enasidenib, and gemtuzumab.

In response to consolidation therapy, 27 of the 83 patients with measurable residual disease became negative by that technique. Of the 35 patients whose MRD had been detected by multiparameter flow, 17 or nearly 50% became MRD negative. Of the 38 who had MRD detected by next-generation sequencing, six became MRD negative after consolidation. And of the 10 patients who had MRD detected by quantitative PCR, six of these patients became MRD negative. So I think what this study shows is that consolidation can induce MRD negativity and it forms a benchmark for further trials that will be addressing measurable residual disease in first remission after induction therapy.

A multivariable logistic regression was done, although the sample size was small. Older age led to a decreased likelihood of conversion to MRD negative. Also, higher ELN risk category, as you would expect, might have had some impact. But actually, here in this multi-variable analysis, high ELN risk category, high dose cytarabine and the number of cycles did not seem to produce a statistically significant increased likelihood of either persistence of measurable disease or reversion to an MRD negative state.