Blinatumomab-chemo boosts survival in MRD-negative B-lineage ALL

The addition of blinatumomab to chemotherapy extended overall survival (OS) in adults with measurable residual disease (MRD)-negative B-lineage acute lymphoblastic leukaemia (ALL), according to results of the phase III ECOG-ACRIN E1910 trial.

“Our study shows that adding blinatumomab to chemotherapy keeps patients in remission and improves their survival,” remarked Professor Mark Litzow from the Mayo Clinic in Rochester, Minnesota, US, who presented the findings at ASH 2022.

Study participants were 488 adults aged 30–70 years (median age 51 years) with newly diagnosed BCR::ABL1 negative B-lineage ALL who had received combination induction chemotherapy for 2.5 months (patients aged <55 years received pegaspargase and CD20+ patients also received rituximab). The 81 percent of patients in morphologic complete remission (CR/CRi) following induction therapy received intensive high-dose methotrexate with pegaspargase.

Following MRD assessment via bone marrow biopsy conducted at a centralized laboratory, patients who were MRD-negative (<0.01 percent; n=224) were randomized 1:1 to receive either an additional four cycles of consolidation chemotherapy alone or two cycles of intravenous blinatumomab (4-week cycles) followed by three cycles of consolidation chemotherapy, another 4-week cycle of blinatumomab, followed by an additional cycle of chemotherapy and another cycle of blinatumomab (total of four blinatumomab cycles). All patients then received maintenance POMP therapy for 2.5 years calculated from the onset of intensive therapy.

Twenty-two patients in each arm underwent allogeneic hematopoietic stem cell transplantation at the discretion of the treating physician. The suggested time for this procedure was after the first two cycles of blinatumomab among patients assigned to the blinatumomab + chemotherapy arm or after the intensive chemotherapy regimen among those assigned to the chemotherapy-only arm.

After a median follow-up of 43 months, there was a significant improvement in OS among those who received blinatumomab + chemotherapy compared with chemotherapy only (median not reached [NR] vs 71.4 months; hazard ratio [HR], 0.42, 95 percent confidence interval [CI], 0.24–0.75; p_two-sided=0.003), with 3.5-year OS rates of 83 percent vs 65 percent. [ASH 2022, abstract LBA1]

Relapse-free survival was also in favour of the blinatumomab + chemotherapy vs chemotherapy-only arm (median NR vs 22.4 months; HR, 0.46, 95 percent CI, 0.27–0.78; p=0.004).

The combination was generally well tolerated, with no new safety signals identified, noted Litzow.

“Adults with newly diagnosed ALL can achieve a high rate of CR with conventional chemotherapy, but frequently relapse and have suboptimal survival rates even if their MRD status is negative after induction,” said Litzow and co-authors.

“We think we can do better, so we wanted to see if blinatumomab would improve the results in this already somewhat favourable risk group, and the study showed that it did,” said Litzow. “Based on what we’re finding, I think this is the new standard of care,” he highlighted.

“We think that adding blinatumomab earlier in the treatment course may be beneficial, and there are studies that are beginning to look at that. We’re also incorporating this into the other new modalities of therapy … that are involved in the treatment of B-lineage ALL,” Litzow concluded. [https://ascopost.com/videos/2022-ash-annual-meeting-and-exposition/mark-litzow-on-all-consolidation-therapy-with-blinatumomab-improves-overall-survival/, accessed 30 December 2022]