Lenalidomide-associated B-cell acute lymphoblastic leukemia in a multiple myeloma patient: a case report

Multiple myeloma (MM) is a clonal plasma cell malignancy often treated with multidrug regimens and autologous stem cell transplantation (ASCT), followed by maintenance therapy with lenalidomide. While lenalidomide has proven efficacy in prolonging remission, it is associated with a rare but significant risk of second primary malignancies, including therapy-related B-cell acute lymphoblastic leukemia (B-ALL).

We report the case of a 73-year-old white American male diagnosed with IgA kappa MM in 2020, treated with six cycles of Bortezomib, Dexamethasone, and Lenalidomide, followed by maintenance lenalidomide therapy. In June 2023, the patient presented with thrombocytopenia during routine follow-up. Bone marrow biopsy confirmed B-ALL, with flow cytometry revealing a neoplastic population consistent with B-lymphoblasts. Lenalidomide was discontinued, and the patient commenced R-hyper-CVAD chemotherapy followed by intrathecal methotrexate. Despite initial plans for allogeneic stem cell transplantation, the procedure was delayed due to persistent COVID-19 positivity. The patient achieved complete remission of B-ALL and opted for surveillance only, prioritizing quality of life.

This case highlights the potential for B-ALL as a secondary malignancy in patients on lenalidomide maintenance therapy, in a relatively short time, without prior ASCT. Early recognition of unexplained cytopenia in such patients is critical, necessitating prompt evaluation with bone marrow biopsy. Further research is needed to elucidate the mechanisms underlying lenalidomide-associated secondary malignancies and optimize patient management strategies.