After treatment with blinatumomab, most patients with minimal residual disease–positive acute lymphoblastic leukemia (ALL) achieved complete MRD response, according to results of a single-arm phase 2 study.

Achieving complete MRD response was associated with significantly longer relapse-free and overall survival in the patients, who were already in hematologic complete remission, researchers reported in the journal Blood.

“Our results suggest that targeted treatment in early stages of MRD is a viable therapeutic strategy for patients with B-cell precursor ALL and that it should also be evaluated in other hematologic malignancies,” Nicola Gökbuget, MD, University Hospital, Frankfurt, Germany, and her coauthors wrote.

This is the first international multicenter study to specifically enroll MRD-positive ALL patients and evaluate them for an MRD-based primary outcome in a cohort of MRD-positive ALL patients, according to the authors.

Preemptively treating low but measurable disease in ALL in remission, instead of waiting for overt relapse, is a strategy that may prolong overall survival, Dr. Gökbuget and her colleagues said in describing the rationale for their study. While there is no standard therapy yet for ALL patients with detectable MRD after intensive chemotherapy, hematopoietic stem cell transplantation (HSCT) is recommended, based on data that it may improve outcomes in patients with persistent MRD. However, other studies suggest detectable MRD before HSCT is associated with higher relapse rates, and many patients relapse while waiting for HSCT, the researchers noted.

To test an MRD-directed treatment strategy, Dr. Gökbuget and colleagues at 46 centers in Europe and Russia conducted an open-label, single-arm, phase 2 study including 116 patients with B-cell precursor ALL in hematologic complete remission. Patients in the study received up to four cycles of blinatumomab, a bispecific, T cell–engager antibody construct that enables T cells to recognize and eliminate CD19-positive cells.

Of 113 evaluable patients, 88 (78%) achieved complete MRD response after one cycle, the primary end point of the study. Relapse-free survival at 18 months was estimated at 54% and median overall survival was 36.5 months in the subset of 110 patients with Philadelphia chromosome–negative ALL in hematologic remission.

Complete MRD responders had improved relapse-free survival versus MRD nonresponders (23.6 vs. 5.7 months; P = .002), they reported. Likewise, overall survival was improved for MRD responders (38.9 vs. 12.5 months; P = .002).

Adverse events were consistent with what was previously reported for blinatumomab and included grade 3 and 4 neurologic events in 12 patients (10%) and 3 patients (3%), respectively. Cytokine-release syndrome was seen in four patients, with grade 1 and grade 3 cases.

The study was not designed to assess the impact of HSCT, which most patients (n = 76) underwent. However, a number of patients with complete MRD response but no HSCT remained in long-term remission, confirming results of an earlier blinatumomab pilot study, according to the researchers.

“This observation might be of relevance for the development of future treatment strategies, particularly for less fit and elderly patients,” Dr. Gökbuget and her coauthors wrote.

Additional studies are needed to clarify the role and indications for HSCT in this setting, they added.

The study was designed by Amgen Research in collaboration with the researchers. Dr. Gökbuget reported financial relationships with Amgen and Pfizer. Other authors reported ties to various pharmaceutical companies.

SOURCE: Gökbuget N et al. Blood. 2018 Apr 5;131(14):1522-31.

Blinatumomab triggers complete MRD response in ALL