New Interfant protocol includes blinatumomab for KMT2A-r ALL

Blinatumomab added to the Interfant-06 backbone protocol was well tolerated and displayed promising efficacy data in infants with newly diagnosed KMT2A-rearranged acute lymphoblastic leukaemia (ALL). Therefore, the new Interfant21 protocol will add blinatumomab to the treatment regimen of these patients [1].

Dr Inge van der Sluis (Princess Máxima Center for Pediatric Oncology, the Netherlands) explained that infants (<1 year) with ALL have a worse prognosis than older children. This is especially true in patients with KMT2A-rearrangement, which is present in 75% of the infants with ALL. Intensifying chemotherapy did not change health outcomes in these patients. Therefore, novel effective therapies are needed for this population.

Blinatumomab is a bispecific T-cell engager that has demonstrated to be safe and efficacious in adults and older children with ALL [2,3]. The current prospective, open-label, non-randomised, multicentre pilot study included 30 patients with newly diagnosed KMT2A-rearranged ALL to be treated with blinatumomab (4-week continuous infusion of 15 μg/m²/day) after induction therapy as described in the Interfant-06 backbone protocol. The primary endpoint was the incidence of clinically relevant toxicities.

All patients received 4 weeks of blinatumomab, demonstrating feasibility of the agent. During blinatumomab therapy, 10 serious adverse events (SAEs) were reported, including 4 infections, 4 cases of fever, 1 case of vomiting, and 1 hypertensive crisis. No neurological SAEs or SUSARS were reported.

Measurable residual disease (MRD) negativity was reported in 27% and 53% of the patients at initiation and after completion of blinatumomab therapy, respectively. Patients receiving blinatumomab had numerically higher MRD negativity rates (79%) than historical controls (63%) at the start of the 5^th treatment period of the Interfant-06 backbone protocol. Assessing patients with MRD negative or positive-non-quantifiable status after blinatumomab therapy did show a significant advantage of blinatumomab (100%) over the historical controls (82%; P=0.02) at the start of the 5^th treatment period.

After a median follow-up of 16.3 months, the 1-year event-free survival (EFS) in patients receiving blinatumomab was 90.0% and the 1-year overall survival (OS) rate was 93.1%. In contrast, historical controls displayed a 1-year EFS rate of 54.8% and a 1-year OS rate of 69.8%. Notably, in the historical controls, most relapses occurred during the first year of therapy. Therefore, it is expected that long-term follow-up data will not significantly change EFS and OS rates in the current study population.

1. Van der Sluis I, et al. A Phase 2 Study to Test the Feasibility, Safety and Efficacy of the Addition of Blinatumomab to the Interfant06 Backbone in Infants with Newly Diagnosed KMT2A-Rearranged Acute Lymphoblastic Leukemia. A Collaborative Study of the Interfant Network. Abstract 361, ASH 2021 Annual Meeting, 11–14 December.
2. Gökbuget N, et al. Blood. 2018;131(14):1522–1531.
3. Locatelli F, et al. JAMA. 2021;325(9):843–854.

 

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Posted on 4 February 202213 May 2022