Prolonged molecular control during intermittent reduced-intensity blinatumomab maintenance in a transplant-ineligible patient with Philadelphia chromosome-positive acute lymphoblastic leukaemia and IKZF1 deletion.

OBJECTIVES

Long-term disease control in transplant-ineligible patients with high-risk Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL) remains difficult, particularly when adverse genetic lesions and acquired kinase domain mutations coexist.

METHODS

Clinical, cytogenetic and molecular records were retrospectively reviewed. BCR::ABL1 transcripts were monitored by quantitative PCR, and peripheral lymphocyte subsets were followed longitudinally. Public transcriptomic data (GSE196463) were analysed to compare T-cell expression profiles under continuous versus intermittent bispecific antibody exposure.

RESULTS

A 64-year-old man with Ph+ ALL harbouring a heterozygous IKZF1 deletion relapsed while receiving dasatinib, with emergence of an ABL1 E255K/V mutation. Although this P-loop mutant retains sensitivity to dasatinib, relapse suggested kinase-independent escape; treatment was redirected towards immune-mediated clearance with one cycle of continuous blinatumomab plus dasatinib, achieving deep molecular remission. Allogeneic transplantation was deferred because of advanced age, prior cardiac dysfunction and cumulative infectious burden, and outpatient maintenance was initiated with monthly 24-h blinatumomab infusions (35 μg) plus dasatinib (100 mg daily) and subcutaneous interferon alfa-2b (3 MIU thrice weekly). Morphologic remission was sustained for over 3.5 years with no unplanned hospitalizations and no grade ≥3 neurotoxicity. BCR::ABL1 transcripts remained undetectable for nearly 3 years before a transient low-level fluctuation (0.0024% IS) appeared and stabilized without treatment escalation. Peripheral monitoring showed persistent CD8+ predominance and sustained B-cell depletion (<20 cells/μL), indicating ongoing target engagement. Public transcriptomic data supported that intermittent bispecific exposure preserves progenitor/memory T-cell programmes while limiting exhaustion.

CONCLUSION

Intermittent reduced-intensity blinatumomab maintenance guided by serial MRD monitoring was feasible and associated with durable molecular control in a transplant-ineligible patient with high-risk Ph+ ALL. This strategy merits prospective evaluation.