Nikolai Podoltsev, MD, PhD, is an associate professor of internal medicine (hematology); Duffy Firm Chief for Education, Department of Internal Medicine; associate director, Hematology/Oncology Fellowship Program, Department of Internal Medicine; clinical director, Malignant Hematology, Department of Internal Medicine, Division of Malignant Hematology, Yale Cancer Center.

- The addition of blinatumomab to consolidation chemotherapy did not show a statistically significant improvement in OS or RFS in older patients with MRD-negative, BCR-ABL1–negative ALL.  - Biologic differences, treatment tolerance, and comorbidities in older patients may contribute to the lack of clear benefit from blinatumomab in this population.  - Further prospective studies are needed to determine the optimal role, sequencing, and long-term efficacy of blinatumomab in older patients with newly diagnosed ALL.

"This [subgroup analysis] is interesting to look at, because it includes patients who are older are, who are in general, more difficult to treat for anything, including B cell ALL."

Nikolai Podoltsev, MD, PhD, associate professor of internal medicine (hematology); Duffy Firm Chief for Education, Department of Internal Medicine; associate director, Hematology/Oncology Fellowship Program, Department of Internal Medicine; clinical director, Malignant Hematology, Department of Internal Medicine, Division of Malignant Hematology, Yale Cancer Center, discusses findings from the phase 3 ECOG-ACRIN E1910 trial (NCT02003222) evaluating the addition of blinatumomab (Blincyto) to consolidation chemotherapy in older patients with newly diagnosed, 

–negative B-lineage acute lymphoblastic leukemia (ALL).

This study enrolled 488 patients, of whom 211 were at least 55 years of age, to assess whether incorporating blinatumomab into consolidation therapy would improve overall survival (OS) and relapse-free survival (RFS) in this patient population. The median follow-up was 54.6 months. Among patients who achieved a response after two cycles of induction (n = 174), 93 were measurable residual disease (MRD)–negative and subsequently randomly assigned to receive blinatumomab plus consolidation chemotherapy (n = 46) or consolidation alone (n = 47).

In this subgroup analysis, no statistically significant improvement in OS or RFS was observed with the addition of blinatumomab, Podoltsev explains. The study was not powered to detect differences in this subset of patients, and exploratory analyses did not identify a clear advantage of blinatumomab in older patients with MRD-negative disease. Among those randomly assigned to blinatumomab, 51.1% completed 4 cycles, and hematopoietic stem cell transplantation was performed in 15.1% of patients on-study and 11.4% off-study.

Regarding safety, blinatumomab was generally well tolerated, with most patients completing therapy as planned. However, the lack of significant OS and RFS benefit may be attributed to biologic differences in older adults, as well as potential disparities in treatment tolerance and modifications, Podoltsev notes. Additionally, older patients with ALL often present with more comorbidities and frailty, which may influence treatment outcomes.

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Nikolai Podoltsev, MD, PhD, discusses the addition of blinatumomab to consolidation chemotherapy in older patients with newly diagnosed BCR-ABL1–negative ALL.

Nikolai Podoltsev, MD, PhD

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Dr Podoltsev on Blinatumomab Plus Consolidation Chemotherapy in Older BCR-ABL1–Negative ALL