Blinatumomab candidate for standard-of-care in newly diagnosed B-ALL 

Patients with newly diagnosed B-lineage acute lymphoblastic leukaemia (B-ALL) who were measurable residual disease (MRD)-negative showed an overall survival (OS) benefit if they were treated with a consolidation therapy of blinatumomab plus chemotherapy compared with chemotherapy alone. These results represent a new potential standard-of-care for this group of patients.

The bi-specific CD19 and CD3 T-cell engager blinatumomab is an approved therapy for patients with relapsed/refractory B-ALL and MRD-positive B-ALL. In MRD-negative patients, the therapy had not yet been thoroughly investigated.

The phase 3 ECOG-ACRIN-E1910 NCTN clinical trial (NCT02003222) exposed patients, aged between 30–70 years, with newly diagnosed B-ALL to 2.5 months of Berlin-Frankfurt-Munster (BFM) induction chemotherapy, modified from the UKALL-XII protocol [1,2]. Those with a complete remission (CR) or a complete remission with incomplete count recovery (CRi) received CNS treatment intensification with high-dose methotrexate plus pegaspargase. Hereafter, the MRD status was assessed, and participants were randomised 1:1 to consolidation chemotherapy plus 4 28-day cycles of blinatumomab or to chemotherapy alone. Finally, all randomised participants received 2.5 years of POMP maintenance chemotherapy. The current study aimed to compare the blinatumomab-containing regimen with the chemotherapy-only arm for OS in MRD-negative patients (n=224). Prof. Mark Litzow (Mayo Clinic, MN, USA) presented the results after a median follow-up time of 43 months.

There was a clear OS benefit for participants in the blinatumomab arm compared with those in the chemotherapy alone arm (median OS: not reached vs 71.4 months; HR 0.42; 95% CI 0.24–0.75; log-rank P=0.003; see Figure). Prof. Litzow added that the 3.5-year OS-rates were 83% and 65%, respectively. Similarly, the relapse-free survival comparison favoured the blinatumomab arm over the chemotherapy arm (not reached vs 22.4 months; HR 0.46; 95% CI 0.27–0.78; log rank P=0.004). Finally, according to Prof. Litzow, the combination therapy was well tolerated and no new safety issues were observed.

Figure: Overall survival comparison in MRD-negative patients [2]



OS, overall survival; Blin, blinatumomab; Chemo, chemotherapy.

Consolidation with blinatumomab and chemotherapy thus demonstrated to provide an OS benefit over chemotherapy alone in newly diagnosed patients with MRD-negative B-ALL, potentially representing a new standard-of-care for this population.

1. Rowe JM, et al. Blood. 2005;106(12):3760–3767.
2. Litzow M, et al. Consolidation Therapy with Blinatumomab Improves Overall Survival in Newly Diagnosed Adult Patients with B-Lineage Acute Lymphoblastic Leukemia in Measurable Residual Disease Negative Remission: Results from the ECOG-ACRIN E1910 Randomized Phase III National Cooperative Clinical Trials Network Trial. Late-Breaking Abstract 1, ASH 64^th Annual Meeting, 10–13 December 2022, New Orleans, LA, USA.

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Posted on 20 February, 202328 March, 2024