Infants with KMT2A-Rearranged Acute Lymphoblastic Leukemia Do Benefit from the Addition of Blinatumomab to Backbone Treatment Protocols

Introduction: KMT2A-rearranged acute lymphoblastic leukemia (ALL) in infants is an aggressive disease with dismal prognosis. Novel approaches, including immunotherapies, offer the potential of improving cure rates. The bi-specific CD3/CD19 engaging antibody, blinatumomab, proved to achieve complete, often minimal residual disease (MRD) negative, remission in infants with B cell acute lymphoblastic leukemia (B-ALL)

Aim: The aim of this report is to present the inclusion of blinatumomab in the treatment schema of infants with B-ALL/Mixed Phenotype Acute Leukemia (MPAL)

Patients and Methods: Our cohort included 4 infants diagnosed with KMT2A rearranged B-ALL/MPAL between 2020-2024, who underwent treatment with blinatumomab during either first line (3 patients) or relapse (1 patient) treatment protocol. Blinatumomab 15 mcg/m² continuous infusion was administered for 1 or 2 cycles. Each cycle consisted of 28 days, and interval between cycles was 14 days. The mean age at first diagnosis was 3.3 months (range: 15 days-6.9 months) and mean age at the time of blinatumomab administration was 8.7 months (range 4.2-15.3 months). MRD was evaluated by fluorescent immunophenotype (FC) and Polymerase Chain Reaction (PCR)-based evaluation of KMT2A rearrangements.

Results: Three patients with pro B-ALL, CNS 3, and 1 patient with MPAL, B/Myelo, CNS 1, are included in our cohort. Bone Marrow karyotype revealed KMT2A rearrangements in all patients, and more specifically: t(4;11) (q21;q23) [2 patients], t(1;11) (p36;q13) t(11;19) (q23;p13.3) [1 patient], and t(11;22) (q23q13) [1 patient with MPAL]. All patients were treated according to the AIEOP BFM 2017 protocol at initial diagnosis. Three patients received blinatumomab either 1 cycle (2 patients) or 2 cycles (1 patient) after the consolidation protocol and as a bridge to hematopoietic stem cell transplantation (HSCT). The fourth patient relapsed after HSCT and received two cycles of Blinatumomab after having received induction /consolidation as per ALL-IC REL 2016 protocol. All patients received the full scheduled courses of blinatumomab. Serious Adverse Events (SAEs) were reported during the first days of infusion (fever requiring hospitalization) in all patients. Short interruption of infusion was required along with a short course of steroids, in one patient. None of the patients presented with neurological SAEs. All the patients were able to be discharged from the hospital after the first week of therapy and they received the remaining infusion in an outpatient basis. All became FC-MRD negative post blinatumomab and prior to HSCT giving a complete MRD response rate of 100%. The median time from commencing blinatumomab to HSCT was 2,3 months (range 1,6-3,2 months). Two patients underwent Matched Sibling HSCT and two Matched Unrelated Donor (MUD) HSCT. Out of the three patients that received blinatumomab before HSCT, 1 remains at first remission 29 months post HSCT and 2 relapsed (9 months and 26 months, respectively post HSCT). The fourth patient relapsed 2,5 months post HSCT and received blinatumomab as described above. All patients who relapsed were able to achieve a second remission with variable schemas. Of note, none of the patients presented relapse with a myeloid lineage switch. With a mean follow-up time of 36,3 months (range 33,5-43,7 months), all patients remain in complete in either 1^st (1patient) or 2^nd (3 patients) remission.

Conclusions: This single institution's cohort from Greece presents the first real world data in using blinatumomab in infant ALL. We have demonstrated that blinatumomab can be safely and effectively administered in infants as either first- or second-line treatment, leading to complete MRD response in all cases, and allowing proceeding to HSCT. The low toxicity and outpatient infusion of blinatumomab concords with improved quality of life for these patients

Kattamis:Vertex Pharmaceuticals: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Steering Committee Membership; Vifor: Consultancy; Agios Pharmaceuticals: Consultancy, Honoraria; Pfizer: Consultancy; Novo Nordisk: Consultancy; Bristol Myers Squibb: Consultancy, Honoraria.