Acute lymphoblastic leukemia following lenalidomide therapy in multiple myeloma patients: Two case reports and review of the literature

Abstract

Background: Lenalidomide, as an immunomodulatory drug, has significantly contributed to advancements in hematologic malignancies. However, lenalidomide therapy has been associated with rare but severe complications, particularly therapy-related acute lymphoblastic leukemia (t-ALL). This study aims to contribute to understanding the clinical, genetic, and therapeutic characteristics of t-ALL following lenalidomide therapy. To achieve this, cases reported in the literature were reviewed, and a comprehensive evaluation was conducted with the addition of two new case reports.

Methods: A comprehensive review of published cases was conducted using databases such as PubMed and Scopus. Inclusion criteria focused on patients who developed ALL following lenalidomide therapy. Clinical findings, cytogenetic data, treatment protocols, and outcomes were analyzed alongside two new cases from our institution.

Results: The findings revealed a diverse genetic landscape among patients with lenalidomide-associated t-ALL, with common abnormalities including TP53 mutations and hypodiploidy. The latency period for developing t-ALL after lenalidomide therapy varied widely, with a median duration of approximately 50 months (range: 6-126). Treatment strategies, such as intensive chemotherapy and allogeneic hematopoietic stem cell transplantation, showed variable efficacy, heavily influenced by cytogenetic risk factors and the presence of infections.

Conclusion: Lenalidomide-associated t-ALL represents a rare but clinically significant complication. Vigilant monitoring, early detection, and personalized therapeutic strategies are crucial for improving outcomes. This study emphasizes the importance of balancing the therapeutic benefits of lenalidomide against its potential risks and advocates for further multicenter studies to refine management protocols and discover predictive biomarkers.

Keywords: Hematopoietic stem cell transplantation; Lenalidomide; Multiple myeloma; Secondary primary malignancies; Therapy-related acute lymphoblastic leukemia.