Blinatumomab triggers complete MRD response in ALL

The study by Dr. Gökbuget and her colleagues provides “strong evidence” that blinatumomab immunotherapy eliminates residual B-cell acute lymphoblastic leukemia (ALL) cells, thereby preventing relapse and improving survival, according to Patrick Brown, MD.

“This addresses the most important unsolved clinical problem in adults with B-ALL: the development of chemotherapy-resistant relapsed disease,” Dr. Brown wrote in an editorial.

Persistence of minimal residual disease (MRD) is the strongest independent predictor of outcomes in B-cell ALL, and is seen in up to 50% of adult patients after chemotherapy, according to Dr. Brown.

The “well-designed and well-executed” multicenter phase 2 study demonstrated an MRD clearance rate of 78% after one cycle of blinatumomab with modest adverse effects, according to Dr. Brown. Moreover, the results show a doubling of overall survival and tripling of relapse-free survival in MRD responders versus nonresponders, he said.

“An important caveat, however, is that, although the MRD clearance rate was no lower in the 35% of patients who had already relapsed once before enrolling, these patients had a substantially inferior RFS [relapse-free survival] and OS [overall survival], compared with those treated in first remission,” he added. “The clear lesson is that the impact of immunotherapeutic clearance of MRD on survival is greatest when applied early in the disease course.

The “most pressing question” not answered by this study is the impact of hematopoietic stem cell transplantation after complete MRD response, since the study allowed optional HSCT.

Patrick A. Brown, MD, is with Johns Hopkins University, Baltimore. These comments are adapted from his editorial in Blood (2018;131:1497-8). Dr. Brown reported having no competing financial interests related to his editorial.