European Commission Approves Blinatumomab Consolidation in Newly Diagnosed CD19+ B-ALL

The European Commission has approved blinatumomab (Blincyto) monotherapy as part of consolidation therapy for the treatment of adult patients with newly diagnosed, Philadelphia chromosome (Ph)–negative, CD19-positive B-cell precursor acute lymphoblastic leukemia (B-ALL).1

The approval of blinatumomab was based on data from the phase 3 ECOG-ACRIN E1910 trial (NCT02003222), which demonstrated superior overall survival (OS) when blinatumomab was added to multiphase consolidation chemotherapy vs chemotherapy alone. At a median follow-up of 4.5 years, the 5-year OS was 82.4% in the blinatumomab plus chemotherapy arm (n = 112) compared with 62.5% in the chemotherapy arm (n = 112).

"This approval represents a significant advancement, offering patients the opportunity to receive [blinatumomab] earlier in their treatment pathway, with the potential to improve outcomes," Jean-Charles Soria, senior vice president of Global Oncology Development at Amgen, the developer of blinatumomab, stated in the news release. "The E1910 data that served as the basis of this approval add to the growing body of evidence of the meaningful survival impact of [blinatumomab]."

In June 2024, the FDA approved blinatumomab for adults and children at least 1 month of age or older with CD19-positive, Ph-negative B-ALL in the consolidation phase, regardless of minimal residual disease (MRD) status.2 This approval was also supported by data from E1910.

E1910 Study Background and Design

The open-label, randomized E1910 study assessed the addition of blinatumomab monotherapy to intensification chemotherapy vs intensification chemotherapy alone in patients newly diagnosed with Ph-negative, CD19-positive B-ALL.3

Eligibility criteria included patients 30 to 70 years of age with newly diagnosed Ph-negative B-ALL made upon bone marrow or peripheral blood immunophenotyping, and an ECOG performance score of 0 to 3.

Prior to being randomly assigned, all patients received induction chemotherapy administration, patients received cytarabine intrathecally (IT) on day 1; daunorubicin hydrochloride intravenously (IV) on days 1, 8, 15, and 22; vincristine sulfate IV on days 1, 8, 15, and 22; oral dexamethasone on days 1-7 (plus days 15 to 21 for patients less than 55 years of age); methotrexate IT on day 14; pegaspargase intramuscularly (IM) or IV on day 18 for patients under 55 years of age; and optional rituximab (Rituxan) IV on days 8 and 15 for patients with CD20-positive disease. Four weeks after the completion of the second cycle of induction therapy, patients received intensification therapy with high-dose methotrexate IV on days 1 and 8 and pegaspargase IM or IV on day 9.

Patients who achieved a complete remission (CR) or CR with incomplete count recovery following induction/intensification therapy were then randomly assigned in a fashion1:1 . In the blinatumomab arm, patients were treated with the agent IV continuously on days 1 to 28. Treatment was repeated every 6 weeks for 2 cycles in the absence of disease progression or unacceptable toxicity. Afterward, patients may undergo an allogeneic stem cell transplant or proceed to consolidation therapy per investigator discretion.

Other consolidation therapy in both arms, which started after the second cycle of blinatumomab for patients in the experimental arm or after intensification therapy for patients in the control arm, patients received cytarabine IV or subcutaneously on days 1 to 5, etoposide IV on days 1 to 5, methotrexate IT on day 1, and pegaspargase IM or IV on day 5; patients with CD20-positive disease could optionally receive rituximab IV on day 5.

The primary end point of the study was OS in patients treated with blinatumomab/chemotherapy vs chemotherapy alone. Secondary end points included relapse-free survival (RFS); the comparison of OS and RFS among patients who are MRD-positive at step 3 randomization or registration and became MRD-negative after 2 cycles of blinatumomab or consolidation chemotherapy; safety and toxicity; and the outcome of patients who proceed to allogeneic transplant after treatment with or without blinatumomab.

Safety data for blinatumomab derived from E1910 were consistent with the known safety profile of the agent.1

“While there has been some treatment progress, many patients with newly diagnosed Ph-negative B-ALL remain at high risk of relapse," Robin Foà, MD, emeritus professor of hematology, Sapienza University of Rome, stated in the news release.1 "The E1910 study results highlight that [blinatumomab] has the potential to advance frontline consolidation treatment, including patients who are MRD-negative, offering a crucial new option to achieve deeper remissions and improve long-term survival.”

References

1. European Commission approves Blincyto (blinatumomab) in patients with Philadelphia chromosome negative minimal residual disease-positive B-cell precursor acute lymphoblastic leukemia. News release. Amgen. January 29, 2025. Accessed January 30, 2025. https://www.prnewswire.com/news-releases/european-commission-approves-blincyto-in-philadelphia-chromosome-negative-cd19-positive-b-cell-precursor-acute-lymphoblastic-leukemia-in-the-consolidation-phase-302363668.html
2. FDA approves Blincyto (blinatumomab) in CD19-positive Philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia (B-ALL) in the consolidation phase. News release. Amgen. June 14, 2024. Accessed January 30, 2025. https://www.amgen.com/newsroom/press-releases/2024/06/fda-approves-blincyto-blinatumomab-in-cd19positive-philadelphia-chromosomenegative-bcell-precursor-acute-lymphoblastic-leukemia-ball-in-the-consolidation-phase
3. Combination chemotherapy with or without blinatumomab in treating patients with newly diagnosed BCR-ABL-negative B lineage acute lymphoblastic leukemia. ClinicalTrials.gov. Updated January 24, 2025. Accessed January 30, 2025. https://clinicaltrials.gov/study/NCT02003222