Evaluating Alemtuzumab in Adult ALL: Insights from a Phase 1/2 Clinical Trial

Evaluating Alemtuzumab in Adult ALL: Insights from a Phase 1/2 Clinical Trial
Acute lymphoblastic leukemia (ALL) in adults remains a highly aggressive malignancy, with long-term survival outcomes limited by treatment resistance and toxicity. However, CD52—a cell-surface antigen expressed in most B- and T-lineage ALL cases—was identified as a possible therapeutic target, offering the potential for new treatment pathways.

One emerging pathway is alemtuzumab, a humanized immunoglobulin G1 monoclonal antibody targeting CD52, which was evaluated in a phase 1/2 study to determine its feasibility and potential efficacy when intercalated into an intensive chemotherapy regimen. Read on to learn more about this study and its potential impacts on clinical practice.

Design of the Clinical Trial
Starting with its design, this study enrolled 295 evaluable adult ALL patients across two phases:

• Phase 1 assessed the tolerability of subcutaneous alemtuzumab at escalating doses—10 mg, 20 mg, and 30 mg—three times weekly for four weeks. A dose of 30 mg was deemed tolerable.
• Phase 2 examined the feasibility of integrating alemtuzumab into chemotherapy regimens by measuring overall survival (OS), disease-free survival (DFS), and adverse events, particularly cytomegalovirus (CMV) viremia.

Only 88 patients of the 295 enrolled were CD52+ at diagnosis and had completed the first three treatment modules, therefore becoming eligible to receive alemtuzumab.

Findings from the Clinical Trial

Looking at the results, key findings from this group first noted that there was no survival benefit  observed from adding alemtuzumab. Landmark analysis at the fourth treatment module showed no significant difference in OS or DFS between patients who received alemtuzumab and those who did not.

The results also showed that CMV viremia was a notable adverse event, occurring in 23.3 percent (14/60) of patients during alemtuzumab treatment and increasing to 29.2 percent (19/65) post-treatment. Despite these complications, alemtuzumab was considered feasible to administer within an intensive chemotherapy regimen.

Discussion and Clinical Implications of the Findings
The findings indicate that while alemtuzumab was successfully administered in adult ALL patients, it did not confer a survival advantage. The high incidence of CMV viremia suggests that alemtuzumab may contribute to immune suppression, necessitating vigilant monitoring and prophylactic measures. Given that landmark analysis revealed no OS or DFS benefit, further investigation into the role of CD52-directed therapies in ALL is warranted, particularly in combination with novel agents such as chimeric antigen receptor (CAR) T-cell therapies or bispecific T-cell engagers.

For oncologists, these results emphasize the importance of biomarker-driven treatment strategies and careful assessment of immunotherapy-related toxicities. The lack of survival benefit with alemtuzumab in this study underscores the need to explore alternative targeted therapies and immune-modulating strategies to improve outcomes in adult ALL.

Reference:

Luskin MR, Yin J, Lozanski G, et al. Results of Cancer and Leukemia Group B 10102 (Alliance), a Phase 1/2 Study [published correction appears in Cancer. 2025 Mar 15;131(6):e35803. doi: 10.1002/cncr.35803.]. Cancer. 2025;131(4):e35750. doi:10.1002/cncr.35750