Blinatumomab regimen may lead to ‘diminishing use of transplant’ for ALL subgroup
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NEW ORLEANS — Blinatumomab extended survival when combined with chemotherapy for adults with minimal residual disease-negative, B-lineage acute lymphoblastic leukemia, according to a study presented at ASH Annual Meeting and Exposition.
“We feel that this represents a new standard of care for these patients and should be incorporated into their standard therapy,” Mark R. Litzow, MD, professor of medicine in the division of hematology at Mayo Clinic in Rochester, Minnesota, said during a press conference.
Background
Blinatumomab (Blincyto, Amgen), a bispecific T-cell engager molecule, combines the variable region of one antibody directed at CD19 on leukemia cells and another antibody directed at CD3 on T cells. The agent has been FDA approved for patients with relapsed or refractory B-lineage ALL and those who are in morphologic remission but have small amounts of disease in their bone marrow.
In the current study, Litzow and colleagues tested blinatumomab among 224 patients with MRD negativity.
Methodology
Patients received standard induction chemotherapy for about 2 months to induce remission, followed by a 1-month course of intensification chemotherapy. Researchers tested patients for MRD before randomly assigning them in a 1:1 ratio to two monthly cycles of blinatumomab via IV, four monthly cycles of consolidation chemotherapy and another two monthly cycles of blinatumomab or four monthly cycles of consolidation chemotherapy. All patients received maintenance chemotherapy for 2.5 years.
“Patients could go off and have a bone marrow transplant if their doctor felt that was in their best interest,” Litzow said.
Median follow-up was 43 months.
Key findings
Results showed longer OS among patients who received blinatumomab with chemotherapy vs. standard chemotherapy alone (median, not reached vs. 71.4 months; HR = 0.42; 95% CI, 0.24-0.75).
Seventeen patients in the blinatumomab group and 39 patients in the chemotherapy group had died by the third interim analysis. About half of the deaths in each group were due to relapse.
Clinical implications
Litzow said the results could lead to “diminishing use of transplant in this setting.”
“Given the survival curve you saw, it’s pretty hard to beat that with a transplant,” he said.
Perspective
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Xiaoyi Chen, MD, PhD, and Jaime Andres Suarez Londono, MD
The results of this trial are very impressive, as Litzow and colleagues showed the addition of blinatumomab to consolidation chemotherapy significantly improved survival. More importantly, the survival curve appeared to plateau about 3 years from consolidation in the experimental arm, suggesting blinatumomab is likely leading to a deeper remission beyond the current threshold of MRD tests vs. cure of leukemia in these patients.
With the trial result nicely demonstrating the benefit of adding blinatumomab to consolidation therapy in MRD-negative patients, clinical practice undoubtedly will be impacted, leaning toward adding blinatumomab in upfront treatment instead of using it only in relapsed/refractory or MRD positive patients.
Given the impressive survival benefit observed in this trial, the role of bone marrow transplant in this group of patients is worth further investigation. Next steps that would be interesting to explore include finding a better way to triage patients to bone marrow transplantation, such as patients who may be high risk or resistant to upfront blinatumomab treatment, and maximizing the use of blinatumomab, such as by adding it to the maintenance stage to further improve outcome. It also is important to take into consideration the patient’s preference for treatment with blinatumomab given in a continuous infusion mode, as well as financial burdens when using an expensive drug.
Collapse
Litzow, MR, et al. Abstract LBA-1. Presented at: ASH Annual Meeting and Exposition; Dec. 10-13, 2022; New Orleans.
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