Inotuzumab Ozogamicin as First-Line Therapy in Acute Lymphoblastic Leukemia

Clin Lymphoma Myeloma Leuk. 2025 May;25(5):e302-e309. doi: 10.1016/j.clml.2024.12.016. Epub 2025 Jan 8.

Abstract

The long-term outcome of older patients with acute lymphoblastic leukemia (ALL) is poor due to a reduced ability to tolerate intensive chemotherapy, a more aggressive disease biology, and the presence of comorbidities. Older adults with Philadelphia chromosome-negative (Ph-) B-cell ALL have the highest rates of treatment failure and complications, and the pediatric-inspired regimens that are effective in younger adults are severely limited by their toxicity in older patients. Targeted therapies, including inotuzumab ozogamicin (InO) and blinatumomab, have potent activity in B-cell ALL and are used today as single agents, and in combination with chemotherapy in both salvage and frontline ALL therapy. Optimized frontline use of B-cell targeting agents would potentially reduce the need for, and exposure to, conventional chemotherapy and improve the tolerance and efficacy of reduced-intensity chemotherapy regimens combined with targeted therapies. This review summarizes the efficacy and safety results of several recent trials investigating different approaches with InO as first-line therapy in patients with Ph- B-cell ALL.

Keywords: Chemotherapy; Frontline therapy; Older patients; Philadelphia chromosome-negative; Targeted therapy.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents, Immunological* / pharmacology
  • Antineoplastic Agents, Immunological* / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Humans
  • Inotuzumab Ozogamicin* / pharmacology
  • Inotuzumab Ozogamicin* / therapeutic use
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / drug therapy
  • Treatment Outcome

Substances

  • Inotuzumab Ozogamicin
  • Antineoplastic Agents, Immunological