Blinatumomab Approved as Consolidation for CD19-Positive, Philadelphia Chromosome–Negative B-Cell Precursor Acute Lymphoblastic Leukemia

Tristan Knight, MD, FRCPC.

The FDA has granted approval to blinatumomab (Blincyto®, Amgen Inc.) for adult and pediatric patients ≥1 month of age with CD19-positive, Philadelphia chromosome–negative B-cell precursor acute lymphoblastic leukemia (Ph-negative BCP ALL) in the consolidation phase of multiphase chemotherapy.

Why it matters

  • Adults: “At its core, cancer can be conceptualized as a failure of the immune system to detect and destroy malignant cells. Blinatumomab can be imagined as ‘righting a wrong’—repurposing and redirecting a patient’s immune system to seek out and remove cancer cells via its unique mechanism of action,” said Tristan Knight, MD, FRCPC, an Oncology Data Advisor Editorial Board Member and Clinical Assistant Professor at Seattle Children’s Hospital. “The integration of blinatumomab into frontline consolidation chemotherapy represents a marked improvement in the standard of care”
  • Children: “The treatment of children with relapsed B-ALL can be extremely challenging. Fortunately, incredible progress is being made in this area – with blinatumomab being a key advance. The results of the phase 3 randomized clinical trial Study 20120215 (NCT02393859) typify this and were instrumental in achieving its FDA approval for pediatric patients,” continued Dr. Knight. “In this study, children received two cycles of conventional chemotherapy followed by a third cycle of either blinatumomab or chemotherapy, prior to undergoing allogeneic hematopoietic stem cell transplant. After five years of follow-up, the relapse-free survival rate for children who received blinatumomab was more than double that of children who received conventual chemotherapy (61% vs 28%), and the overall survival was nearly double (78% vs 41%). The achievement of pre-transplant remission is a critical component of therapy—and blinatumomab is very effective at obtaining this”

What they studied: Efficacy was measured in two studies, the first being the E1910 study (NCT02003222), a phase 3 assessment of 224 patients with newly diagnosed Ph-negative BCP ALL who were randomized 1:1 to receive either a consolidation regimen comprised of multiple blinatumomab monotherapy cycles plus multiple cycles of intensive chemotherapy or intensive chemotherapy alone. Patients were randomized based on age, CD20 status, rituximab use, and intent to undergo allogeneic hematopoietic stem cell transplantation (HSCT). Eligibility was stratified by patients in hematologic complete remission or complete remission with incomplete peripheral blood count recovery following induction and intensification chemotherapy.

The primary efficacy outcome measured in this study was overall survival.

The second study assessed was Study 20120215 (NCT02393859), a phase 3, open-label, multicenter trial in which 111 pediatric and young adult patients with Ph-negative BCP ALL were randomized 1:1 to receive either blinatumomab or the IntReALLHR2010 HC3 intensive combination chemotherapy as the third consolidation cycle. Patients were randomized based on age, minimal residual disease status at the end of induction based on local assessment, and bone marrow status at the end of the second block of consolidation chemotherapy.

The primary efficacy outcome measured in this study was overall survival and relapse-free survival.

What they found: In the E1910 study, the three-year overall survival of patients receiving blinatumomab was 85% in comparison with those receiving chemotherapy alone who saw a three-year overall survival of 69%. With a median follow-up of 4.5 years in a later analysis, the five-year overall survival was 82% in the blinatumomab arm compared with 63% in the chemotherapy arm.

In the 20120215 study, the five-year overall survival was 78% in the blinatumomab arm compared with 41% in the chemotherapy arm. In addition, the relapse-free survival results at the five-year mark were 61% in the blinatumomab arm compared with 28% in the chemotherapy arm.

Adverse events: In the E1910 study, the most common adverse events experienced by ≥20% receiving blinatumomab were neutropenia, thrombocytopenia, anemia, leukopenia, headache, infection, nausea, lymphopenia, diarrhea, musculoskeletal pain, and tremor.

In the 20120215 study, the most common adverse events experienced in ≥20% receiving blinatumomab were pyrexia, nausea, headache, rash, hypogammaglobulinemia, and anemia.

Safety concerns—well worth the risks: “As an immune effector cell therapy, blinatumomab carries a unique set of potential side effects: specifically, the occurrence of cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS),” concluded Dr. Knight. “Both toxicities are intrinsically linked to blinatumomab’s mechanism of action—eg, the targeting of leukemic cells by the patient’s own immune system. While these side effects can be life-threatening, severe manifestations are relatively rare and can be effectively managed. Also, given how difficult it is to cure the primary disease, these risks are well worth the benefit obtained. Clinicians must always maintain a high degree of vigilance, however, when using blinatumomab.”

Instructions: The recommended dosage of blinatumomab is based on the patient’s weight and schedule. Please refer to the prescribing information for recommended dosage instructions.

For More Information

Luger S, Sun Z, Mattison R, et al (2023). Assessment of outcomes of consolidation therapy by number of cycles of blinatumomab received in newly diagnosed measurable residual disease negative patients with B-lineage acute lymphoblastic leukemia: In the ECOG-ACRIN E1910 randomized phase III National Clinical Trials Network trial. Blood, 142(suppl_1): 2887. DOI:10.1182/blood-2023-189648

Locatelli F, Zugmaier G, Rizzari C, et al (2021). Effect of blinatumomab vs chemotherapy on event-free survival among children with high-risk first-relapse B-cell acute lymphoblastic leukemia: A randomized clinical trial. JAMA, 325(9):843-854. DOI:10.1001/jama.2021.0987

Blincyto® (blinatumomab) prescribing information (2024). Amgen Inc. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/125557s028lbl.pdf

Clinicaltrials.gov (2023). Combination chemotherapy with or without blinatumomab in treating patients with newly diagnosed BCR-ABL-negative B lineage acute lymphoblastic leukemia. NLM identifier: NCT02003222.

Clinicaltrials.gov (2024). Phase 3 trial of blinatumomab vs standard chemotherapy in pediatric subjects with high-risk (HR) first relapse B-precursor acute lymphoblastic leukemia (ALL). NLM identifier: NCT02393859.

US Food and Drug Administration (2024). FDA approves blinatumomab as consolidation for CD19-positive Philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-blinatumomab-consolidation-cd19-positive-philadelphia-chromosome-negative-b-cell

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