The addition of blinatumomab (Blincyto) to consolidation chemotherapy conferred a big general survival (OS) profit in contrast with consolidation chemotherapy alone in sufferers with minimal residual illness (MRD)–destructive B-cell precursor acute lymphoblastic leukemia (ALL), in accordance with findings from the section 3 ECOG-ACRIN E1910 trial (NCT02003222) revealed within the New England Journal of Drugs.1
At a median follow-up of 43 months, findings from the third interim efficacy evaluation of E1910 demonstrated that MRD-negative sufferers who obtained the bispecific T-cell engager (n = 112) achieved a 3-year OS price of 85% in contrast with 68% amongst sufferers who obtained consolidation chemotherapy alone (n = 112; HR, 0.41; 95% CI, 0.23-0.73; P = .002). The relapse-free survival (RFS) charges had been 80% vs 64%, respectively (HR, 0.53; 95% CI, 0.32-0.87).
“[This patient population] has historically had a greater prognosis with chemotherapy than sufferers who’re MRD constructive after induction chemotherapy, however lots of them can nonetheless relapse,” Mark R. Litzow, MD, lead examine creator and a professor of medication (now retired) on the Mayo Clinic in Rochester, Minnesota, defined in an interview with OncLive®. “We needed to see if including blinatumomab to their chemotherapy routine would go after any leukemia cells that had been remaining that we weren’t detecting, [thus] enhancing their survival. Certainly, we discovered that including blinatumomab to the chemotherapy routine did reduce their threat of relapse and enhance their survival. We consider this can be a new customary of care.”
On June 14, 2024, blinatumomab was granted approval by the FDA for the therapy of grownup and pediatric sufferers aged 1 month or older with CD19-positive, Philadelphia chromosome (Ph)–destructive, B-cell precursor ALL within the consolidation section, no matter MRD standing. The regulatory determination was supported by preliminary findings from E1910.2,3
E1910 enrolled sufferers who had been 30 to 70 years of age with BCR::ABL1-destructive B-cell precursor ALL who achieved MRD-negative remission, outlined as lower than 0.01% leukemic cells within the bone marrow per movement cytometry after induction and intensification chemotherapy. Sufferers had been randomly assigned to obtain 4 cycles of chemotherapy plus 4 cycles of blinatumomab. Blinatumomab was administered at a dose of 28 μg per day for 4 weeks, with a 2-week interval between cycles, adopted by 4 cycles of chemotherapy and a pair of further cycles of blinatumomab, or 4 cycles of consolidation chemotherapy solely. Stratification occurred based mostly on affected person age (30 to 54 years or ≥ 55 years), CD20 standing (constructive or destructive), rituximab (Rituxan) use (sure or no), and whether or not transplantation was meant (sure or no).1
The first finish level was OS within the MRD-negative subgroup. RFS represented a secondary finish level.
At baseline, the median age was 51.5 years (vary, 30-69) vs 50 years (vary, 30-70) within the mixture and chemotherapy-only arms, respectively. Most sufferers in each arms had an ECOG efficiency standing of 1 or much less (95% vs 90%), didn’t intend to endure transplantation at random project (68% vs 69%), and had a CD10-positive, early pre-B immunophenotype (85% vs 83%). Sufferers in each arms had favorable (17% vs 26%), intermediate (20% vs 17%), unfavorable (45% vs 39%), and no threat assigned (19% vs 18%) mixed threat illness.
Extra findings from a multivariable evaluation of E1910 adjusting for intercourse, white cell depend, platelet depend, hemoglobin degree, peripheral blood blasts, bone marrow blasts, ECOG efficiency standing, and mixed molecular threat class revealed that the addition of blinatumomab to consolidation chemotherapy lowered the danger of loss of life vs consolidation chemotherapy alone by 56% (HR, 0.44; 95% CI, 0.23-0.81). The addition of blinatumomab additionally provided a big RFS profit vs chemotherapy alone (HR, 0.57; 95% CI, 0.33-0.98).
Amongst sufferers who had been youthful than 55 years previous (n = 132), important OS (HR, 0.16; 95% CI, 0.05-0.47) and RFS (HR, 0.31; 95% CI, 0.14- 0.69) advantages had been noticed with the addition of blinatumomab. Equally, sufferers 55 years of age or older (n = 93) additionally skilled OS (HR, 0.66; 95% CI, 0.33-1.35) and RFS (HR, 0.74; 95% CI, 0.39-1.43) advantages when blinatumomab was added to consolidation chemotherapy.
“E1910 is the primary randomized trial to exhibit that we’re in a position to enhance the survival of adults with B-cell precursor ALL who’re in full remission, together with by delicate MRD testing, and establishes the addition of blinatumomab immunotherapy to straightforward consolidation chemotherapy as a therapy that may change scientific apply,” Selina M. Luger MD, FRCPC, examine coauthor and chair of the ECOG-ACRIN Leukemia Committee, in addition to a professor of medication (Hematology-Oncology) on the Hospital of the College of Pennsylvania, in Philadelphia, mentioned in a press launch.2
By way of security, grade 3, 4, and 5 nonhematologic treatment-related hostile results (TRAEs) occurred at charges of 43%, 14%, and a pair of%, respectively, amongst sufferers within the blinatumomab arm. These TRAEs had been reported at charges of 36%, 15%, and 1%, respectively, within the management arm (P =.17). Grade 3 anemia (20% vs 35%), febrile neutropenia (16% vs 21%), and thrombocytopenia (9% vs 10%) had been current in each the investigational and management arms, respectively.
“We’re going to be [examining] incorporating blinatumomab earlier into therapy,” Litzow mentioned. “I consider we may additionally be capable to cut back the quantity of chemotherapy sufferers obtain given the efficacy of [agents such as blinatumomab]. We’re going to see a larger use of those brokers and lessening the usage of chemotherapy. However now we have to be cautious in doing this as a result of we don’t need to make dramatic modifications after which discover out that they essentially don’t work. [However], the overall development will likely be to make larger use of those brokers.”
References
- Litzow MR, Solar Z, Mattison RJ, et al. Blinatumomab for MRD-negative acute lymphoblastic leukemia in adults. N Engl J Med. 2024;391:320-333. doi:10.1056/NEJMoa2312948
- New England Journal of Drugs publishes outcomes from practice-changing E1910 trial for sufferers with BCR::ABL1-negative B-cell precursor acute lymphoblastic leukemia. Information launch. ECOG-ACRIN Analysis Group. July 24, 2024. Accessed July 24, 2024. https://www.eurekalert.org/news-releases/1051981
- FDA approves Blincyto (blinatumomab) in CD19-positive Philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia (B-ALL) within the consolidation section. Information launch. Amgen. June 14, 2024. Accessed July 24, 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
