Minimal residual disease influences outcomes in relapsed, refractory ALL

Minimal residual disease negativity correlated with long-term survival in patients with relapsed and refractory acute lymphoblastic leukemia in first salvage, according to retrospective study results.

However, the majority of patients in second salvage had poor outcomes regardless of minimal residual disease (MRD) status.

MRD status can be used to predict outcomes in patients with newly diagnosed ALL; however, its function in patients with relapsed and refractory disease has not been fully determined.

Elias Jabbour, MD, associate professor in the department of leukemia at The University of Texas MD Anderson Cancer Center, and colleagues retrospectively reviewed data from 78 patients (median age, 38 years; range, 18-87) with relapsed and refractory B-cell ALL to determine the prognostic effect of MRD assessment in this patient population.

Patients achieved remission with first (n = 46) or second (n = 32) salvage therapy with inotuzumab ozogamicin (CMC-544, Pfizer; n = 41); blinatumomab (Blincyto, Amgen; n = 11); or multihyperfractionated cyclophosphamide, vincristine and doxorubicin with inotuzumab ozogamicin (n = 26).

MRD assessment by multiparameter flow cytometry occurred at the time of remission.

Median follow-up was 27 months (range, 6-55).

Fifty-three percent of patients (n = 41) tested negative for MRD, including 26 patients (57%) who achieved remission after first salvage and 15 patients (47%) who achieved remission after second salvage.

Among MRD–negative patients, those who achieved remission in first salvage demonstrated significant benefits in EFS (median, 18 months vs. 5 months; P = .001) and OS (median, 27 months vs. 7 months; P = .01) compared with those who achieved remission in second salvage.

Further, MRD–negative patients who achieved remission in first salvage had better EFS (median, 18 months vs. 7 months; 2-year EFS, 46% vs. 17%) and OS (median, 27 months vs. 9 months; 2-year OS, 52% vs. 36%) than MRD–positive patients. Conversely, patients who achieved remission in second salvage demonstrated similar EFS and OS outcomes regardless of MRD status.

A subgroup analysis of 11 patients who previously underwent hematopoietic stem cell transplantation showed the eight MRD–negative patients achieved longer OS (39 months vs. 8 months; P = .04) and EFS (18 months vs. 8 months; P = .01) than the three MRD–positive patients.

Among patients who proceeded to HSCT after salvage therapy, MRD–negative patients who underwent HSCT after first salvage achieved better EFS (P = .003) and OS (P = .04) than those who underwent HSCT after second salvage.

The researchers acknowledged study limitations, including the failure of the survival analysis based on MRD negativity to reach statistical significance.

Further, because the researchers assessed MRD status only at the time of remission, they could not determine the optimal time for such an assessment.

“The achievement of MRD negativity is an important therapeutic outcome in the relapsed [and] refractory setting, but has a differential prognostic impact based on the salvage status,” Jabbour and colleagues wrote. – by Cameron Kelsall

Disclosure: Jabbour and one other study researcher report grants from Amgen and Pfizer. The other researchers report no relevant financial disclosures.