FDA Approves Blinatumomab for CD19+ B-ALL in the Consolidation Phase

FDA

The FDA has approved blinatumomab (Blincyto) for the treatment of adult and pediatric patients aged 1 month or older who have CD19-positive, Philadelphia chromosome (Ph)–negative, B-cell precursor acute lymphoblastic leukemia (B-ALL) in the consolidation phase, irrespective of measurable residual disease (MRD) status.^1,2

The decision is supported by data from the phase 3 ECOG-ACRIN E1910 study (NCT02003222), in which the addition of blinatumomab to multiphase consolidation chemotherapy (n = 112) resulted in a superior overall survival (OS) benefit vs chemotherapy alone (n = 112), with 3-year OS rates of 84.8% (95% CI, 76.3%-90.4%) and 69% (95% CI, 58.7%-77.2%), respectively.

At a median follow-up of 4.5 years, the respective 5-year OS rates were 82.4% (95% CI, 73.7%-88.4%) and 62.5% (95% CI, 52.0%-71.3%), respectively. The hazard ratio for OS was 0.44 (95% CI, 0.23-0.76; P = .003).

"In the E1910 study, blinatumomab reduced risk of death and showed a remarkable improvement in overall survival," Selina M. Luger, MD, professor of hematology-oncology at the University of Pennsylvania's Perelman School of Medicine and Abramson Cancer Center, chair of the ECOG-ACRIN Leukemia Committee, and study investigator, stated in a press release. "This approval redefines the standard of care for patients with B-ALL and provides them with a more effective treatment option than standard chemotherapy alone."

The efficacy of the agent was also examined in the phase 3 Study 20120215 (NCT02393859).² Data indicated that blinatumomab (n = 54) led to a 5-year OS rate of 78.4% (95% CI, 64.2%-87.4%) vs 41.4% (95% CI, 26.3%-55.9%) with IntReALLHR2010 HC3 intensive combination chemotherapy (n = 57) as the third consolidation cycle (HR, 0.35; 95% CI, 0.17-0.70). The respective 5-year relapse-free survival rates were 61.1% (95% CI, 46.3%-72.9%) and 27.6% (95% CI, 16.2%-40.3%; HR, 0.38; 95% CI, 0.22-0.66).

About E1910: Eligibility, Treatment, Objectives, Patient Characteristics

The randomized, controlled study enrolled patients with newly diagnosed, Ph-negative B-ALL who were in hematologic complete remission (CR) or CR with incomplete peripheral blood count recovery after induction and intensification chemotherapy.³

Participants were randomly assigned 1:1 to receive consolidation treatment with multiple cycles of blinatumomab plus multiple cycles of intensive chemotherapy or intensive chemotherapy alone. They were stratified by age (<55 years vs ≥55 years), CD20 status, rituximab (Rituxan) use, and intent to undergo allogeneic stem cell transplant.

For post-remission treatment, those in the blinatumomab arm received 2 cycles of the agent followed by 3 cycles of consolidation chemotherapy and a third cycle of blinatumomab followed by a fourth cycle of chemotherapy. They then received a fourth cycle of blinatumomab for a total of 8 cycles. Blinatumomab was given intravenously, at a daily dose of 28 mcg for days 1 to 28. Those in the chemotherapy arm received 4 cycles of chemotherapy alone for a total of 4 cycles.

Notably, patients in the experimental arm were able to undergo hematopoietic stem cell transplant (HSCT) following 1 to 2 cycles of blinatumomab and up to 2 cycles of consolidation chemotherapy. Those in the chemotherapy arm were able to go to HSCT following intensification and up to 3 cycles of consolidation chemotherapy. Those who finished consolidation treatment but did not undergo transplant were given maintenance treatment for up to 2.5 years after intensification treatment was initiated.

The median patient age in the blinatumomab and chemotherapy arms was 51 years (range, 30-70). Approximately half of patients were male (49% vs 50%), and most patients were White (78% vs 79%) and were not Hispanic or Latino (85% vs 85%). Moreover, in the blinatumomab arm, 58% of patients were younger than 55 years at the time of randomization, 40% had CD20 positivity, 29% had received rituximab, and 32% were planned to undergo transplant; in the chemotherapy arm, these respective rates were 58%, 41%, 32%, and 31%.

Safety Data from E1910

Two patients on the blinatumomab arm experienced fatal adverse effects (AEs); they experienced infection and coagulopathy. Dose interruptions and reductions of the agent were required in 5% and 28% of patients, respectively. Two percent of patients permanently discontinued treatment due to toxicity.

In the blinatumomab arm, the most common AEs included neutropenia (all grade, 83%; grade 3/4, 77%), thrombocytopenia (75%; 57%), anemia (59%; 29%), leukopenia (43%; 41%), lymphopenia (32%; 30%), febrile neutropenia (19%; 19%), nausea (32%; 5%), diarrhea (29%; 3%), cytokine release syndrome (16%; 4%), infection (35%; 31%), musculoskeletal pain (23%; 5%), headache (41%; 5%), tremor (23%; 3%), aphasia (10%; 8%), and hypertension (12%; 10%).

About Study 20120215: Eligibility, Treatment, Objectives, Patient Characteristics

The randomized, open-label, multicenter study enrolled patients with high-risk, first-relapsed, Ph-negative B-ALL with fewer than 25% blasts in the bone marrow following induction and 2 cycles of consolidation chemotherapy. Patients were between the ages of 28 days and 18 years.

Participants were randomly assigned 1:1 to receive blinatumomab or intensive chemotherapy for their third cycle of consolidation treatment. Those in the investigative arm were given 1 cycle of blinatumomab at a daily dose of 15 mcg/m² over 4 weeks. They were stratified by age, MRD status at the end of induction, and bone marrow status at the end of the second block of consolidation chemotherapy. They proceeded to transplant following the third cycle of consolidation.

The median age across the blinatumomab and chemotherapy arms was 5.5 years (range, 1-17). Most patients were 1 to 9 years of age (72% vs 72%), White (93% vs 81%), and had blasts below 5% at randomization (100% vs 95%). Just over half of those in the blinatumomab arm were male (56%) vs 40% of those in the chemotherapy arm.

Regarding MRD at randomization in the blinatumomab arm, 20% had MRD ≥10^-3, 28% had MRD <10^-3 and ≥10^-4, 37% had MRD <10^-4, and 15% had unknown status; in the chemotherapy arm, these rates were 28%, 11%, 40%, and 21%.

Safety Findings: Study 20120215

Twenty-eight percent of patients who received blinatumomab experienced serious AEs and 4% discontinued due to toxicity. Dose interruptions were required for 11% of patients. The most common AEs experienced with the agent were pyrexia, nausea, headache, rash, hypogammaglobulinemia, and anemia.

References

1. 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 June 14, 2024. 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
2. FDA approves blinatumomab as consolidation for CD19-positive Philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia. FDA. June 14, 2024. Accessed June 14, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-blinatumomab-consolidation-cd19-positive-philadelphia-chromosome-negative-b-cell
3. Blincyto. Prescribing information. Amgen; 2024. Accessed June 14, 2024. https://www.pi.amgen.com/-/media/Project/Amgen/Repository/pi-amgen-com/Blincyto/blincyto_pi_hcp_english.pdf