Frank Keller, MD
E. Anders Kolb, MD
Frank Keller, MD, a pediatric hematologist/oncologist with Children’s Healthcare of Atlanta–Egleston Hospital, and E. Anders Kolb, MD, Director of the Nemours Center for Cancer and Blood Disorders, Nemours Children’s Health System in Delaware, provided comments on the studies for The ASCO Post.
As Dr. Keller pointed out, the study by Locatelli et al was terminated after the first interim analysis showed better event-free survival for blinatumomab vs a third consolidation cycle of chemotherapy in children with B-cell precursor ALL prior to allogeneic stem cell transplant.1 The study is important, he said, in that it supplements the findings of the similarly designed study reported by Brown et al from the Children’s Oncology Group (COG) at the 2019 ASH Annual Meeting & Exposition.2
“Interestingly, the COG study was also terminated early for the high-risk and intermediate-risk cohort at the time of the interim analysis due to improved overall survival and toxicity profile of the blinatumomab arm—although event-free survival trended positively but did not reach statistical significance at the time of the report,” he said. “Taken together, the similar findings from two large cooperative groups from North America and Europe provide evidence that the standard of care for high-risk first relapse of B-cell precursor ALL should include the use of blinatumomab prior to hematopoietic stem cell transplantation.”
“It will be interesting to see the full reports from both of these studies, which may help to better define the role of blinatumomab in some subsets of relapsed patients, such as those with isolated central nervous system relapse or those who have a rapid response to induction therapy as measured by measurable residual disease after completing the reinduction phase of therapy,” Dr. Keller added.
Dr. Kolb commented on the large retrospective analysis by Shah et al, which found the use of blinatumomab before chimeric antigen receptor (CAR) T-cell therapy to be associated with worse outcomes, in particular, increasing the risk of relapse in children with ALL.3 “The authors speculate that sequential immunotherapies targeting the same molecule on the leukemia cells may foster or select cells resistant to these therapies,” he noted.
“The challenge clinically is that both blinatumomab and CAR T cells are highly effective therapies for children with relapsed ALL. Neither may be expendable, but clinicians need to be selective in how they use these therapies sequentially,” Dr. Kolb said. “Future studies may focus on the use of conventional transplant after CAR T-cell therapy to mitigate the impact of prior blinatumomab in patients where the use of both is unavoidable.”
DISCLOSURE: Dr. Keller has served on a scientific advisory committee for Merck. Dr. Kolb has been reimbursed for travel, accommodations, or other expenses by Roche/Genentech.
1. Locatelli F, Zugmaier G, Rizzari C, et al: Superior event-free survival with blinatumomab versus chemotherapy in children with high-risk first relapse of B-cell precursor acute lymphoblastic leukemia: A randomized, controlled phase 3 trial. 2020 ASH Annual Meeting & Exposition. Abstract 268. Presented December 5, 2020.
2. Brown PA, Ji L, Xu X, et al: A randomized phase 3 trial of blinatumomab vs. chemotherapy as post-reinduction therapy in high and intermediate risk first relapse of B-acute lymphoblastic leukemia in children and adolescents/young adults demonstrates superior efficacy and tolerability of blinatumomab: A report from Children’s Oncology Group Study AALL 1331. 2019 ASH Annual Meeting & Exposition. Abstract LBA-1.
3. Taraseviciute A, Steinberg SM, Myers RM, et al: Pre-CAR blinatumomab is associated with increased post-CD19 CAR relapse and decreased event free survival. 2020 ASH Annual Meeting & Exposition. Abstract 269. Presented December 5, 2020.
Monotherapy with blinatumomab as consolidation therapy before allogeneic stem cell transplant appears to be the optimal treatment for children with high-risk first-relapse B-cell precursor acute lymphoblastic leukemia (ALL), according to an international phase III trial that compared this approach...