Hematology (Amsterdam, Netherlands) · 2026
Frontline therapies for adult patients with newly diagnosed Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia: a systematic literature review.
СтатьяСистематический обзорНазвание и аннотация: Перевод в очереди
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Meza Maria Virginia, Hodgkinson Sarah, Eichinger Christian Stefan, Zaman Faraz, Boyko Diana
Аннотация
OBJECTIVES: Philadelphia (Ph) chromosome-negative B-cell acute lymphoblastic leukemia (B-ALL) is the most common ALL in adults. Overall survival (OS) with frontline chemotherapy remains poor. Blinatumomab is currently the only targeted agent approved for frontline treatment.
METHODS: We systematically reviewed 96 studies (43 interventional, 53 observational) between 2012-2026 evaluating frontline pharmacologic therapy in adults with Ph- B-ALL.
RESULTS: Across chemotherapy studies, nearly half of patients relapsed within 3 years, and only 49%-69% survived beyond 3 years. Blinatumomab demonstrated robust and consistent efficacy in first complete response (CR1), supported by 2 randomized controlled trials (RCT) and 16 single-arm trials (SAT). In one RCT, blinatumomab reduced the risk of death by 59% versus chemotherapy alone (HR 0.41) when added to frontline consolidation in minimal residual disease (MRD) negative patients. Median OS reached 41.2 months in a SAT where blinatumomab monotherapy was administered to patients in MRD-positive CR1. SATs showed consistent efficacy outcomes regardless of age, MRD status, or chemotherapy backbone.
DISCUSSION: Additional targeted therapies still under investigation have shown mixed results.
CONCLUSION: Frontline inotuzumab (±blinatumomab) plus chemotherapy showed promise in older populations, while the efficacy benefit of rituximab was inconclusive. No new safety signals were identified in the frontline setting for targeted therapies.
METHODS: We systematically reviewed 96 studies (43 interventional, 53 observational) between 2012-2026 evaluating frontline pharmacologic therapy in adults with Ph- B-ALL.
RESULTS: Across chemotherapy studies, nearly half of patients relapsed within 3 years, and only 49%-69% survived beyond 3 years. Blinatumomab demonstrated robust and consistent efficacy in first complete response (CR1), supported by 2 randomized controlled trials (RCT) and 16 single-arm trials (SAT). In one RCT, blinatumomab reduced the risk of death by 59% versus chemotherapy alone (HR 0.41) when added to frontline consolidation in minimal residual disease (MRD) negative patients. Median OS reached 41.2 months in a SAT where blinatumomab monotherapy was administered to patients in MRD-positive CR1. SATs showed consistent efficacy outcomes regardless of age, MRD status, or chemotherapy backbone.
DISCUSSION: Additional targeted therapies still under investigation have shown mixed results.
CONCLUSION: Frontline inotuzumab (±blinatumomab) plus chemotherapy showed promise in older populations, while the efficacy benefit of rituximab was inconclusive. No new safety signals were identified in the frontline setting for targeted therapies.