Adverse Events in Adults with Relapsed or Refractory Acute Lymphoblastic Leukemia (ALL): A Literature Review of Recent Clinical Trials

Background: With the introduction of new therapy options for adult patients with relapsed or refractory (R/R) acute lymphoblastic leukemia (ALL), a better understanding of existing toxicity profiles is needed. Methods: A systematic literature review was conducted to summarize the toxicity profiles in clinical trials using chemotherapeutic regimens, tyrosine kinase inhibitor (TKI)-based approaches in Philadelphia chromosome-positive (Ph+) and Philadelphia chromosome-negative (Ph-) R/R ALL, or other targeted therapies. Seventeen eligible articles were identified that reported toxicity profiles. We grouped adverse events into the following categories: hematological, infectious, gastrointestinal, cardiovascular/renal/hepatic, and neurological, stratified by treatment type. Treatment-related or early/induction mortality was also summarized. Results: With cytotoxic chemotherapy and its combinations, hematological adverse events were the most common, affecting virtually all patients, followed by infections, which were reported in most patients. Neurologic toxicity was the most common adverse event associated with liposomal vincristine. TKI-based treatments showed a distinct safety profile compared with the chemotherapies. Although hematological adverse events still represented the most common toxicity, infections were less common with TKI-based therapies (9-18%) than with chemotherapies (56-100%). Nausea, vomiting, and diarrhea were the predominant gastrointestinal adverse events after receipt of TKIs, whereas mucositis appeared to be more characteristic of cytotoxic chemotherapy. Conclusions: This paper provides a systematic review of the safety profile of current standard chemotherapy for adults with R/R Phor Ph+ ALL. Overall, documentation of adverse events was highly variable across the studies, precluding direct comparisons or pooling of results. However, this systematic literature review is the first to summarize and quantify the toxicity profiles of mainly chemotherapeutic and TKI-based regimens for adult patients with R/R ALL, providing a baseline for comparison with emerging therapies.