Joseph C. Alvarnas, MD

“Pediatric acute lymphoblastic leukemia (ALL) is the paradigmatic success story in hematology,” said Joseph C. Alvarnas, MD, Professor in the Department of Hematology and Hematopoietic Cell Transplant, Vice President of Government Affairs, and Chief Clinical Advisor for AccessHope at City of Hope in Duarte, California. Based upon data from clinical trials, he noted, “incremental improvements to care have included landmark advances in combination chemotherapeutic regimens, inclusion of immune-oncologic agents in treatment regimens, postinduction intensification, intensive consolidation strategies, and maintenance therapy. Advances in genetic and genomic diagnostic testing, rigorous clinical risk segmentation, and the use of measurable residual disease (MRD) monitoring have culminated in care strategies that now routinely produce long-term remission rates above 90%.”

Dr. Alvarnas added: “While improvements in adult outcomes have roughly paralleled those of pediatrics patients, survival rates for adults remain significantly inferior. Some subsets of adult patients—like those with Philadelphia chromosome (Ph)-positive ALL—enjoy markedly improved outcomes, but the ideal approach for adult patients with Ph-negative ALL remains far from fully resolved. It is in this context that the ECOG-ACRIN E1910 randomized phase III study from the National Cooperative Clinical Trials Network points toward a new, exciting direction for this population of patients.”

ECOG-ACRIN E1910 assessed the impact of postinduction consolidation with the bispecific antibody blinatumomab in MRD-negative patients, vs standard chemotherapy–based consolidation therapy. As of the third interim study analysis, patients treated in the blinatumomab arm demonstrated a significant improvement in overall survival as compared with conventionally treated patients: median survival was not reached and was 71.4 months with standard treatment.

‘Robust Evidence’

“This trial provides robust evidence for a paradigm shift in the care of adult patients with Ph-negative ALL. This immune-chemotherapeutic–based approach that combines effective, intensive, risk-stratified ALL treatment with bispecific antibody–based immunotherapy represents a significant advance in how we think strategically about managing adults with ALL. Rather than using failure-based treatment-escalation models (treating patients with blinatumomab following either relapse or MRD positivity), this new care paradigm front-loads immunotherapy as a means of preventing relapse and potentially averts the need for transplant as consolidation therapy. This latter consideration merits further validation,” he commented.

Finally, from a global health policy perspective, this trial provides evidence of the value of therapeutic innovation and iterative integration of novel therapeutics into the care of patients being treated for a hematologic malignancy, according to Dr. Alvarnas. “Unfortunately, this innovation comes at a time when discussions regarding the cost of care threaten to drown out those regarding how to deliver the best outcomes,” he noted. “As the specter of brute force cost-cutting methods threatens patient access to this kind of care, this trial provides an important reminder that value in care should be defined in the most patient-centered ways possible.”

Dr. Alvarnas concluded: “As these data rightfully lead to changes in practice, it will be essential to ensure that payers and policymakers understand why these findings are important, so they can ensure all patients with ALL benefit from equitable access to this profound advance in care.” 

DISCLOSURE: Dr. Alvarnas reported no conflicts of interest.