Therapy-related B-cell acute lymphoblastic leukemia after treatment for multiple myeloma

Changing landscape of treatment has significantly improved survival in multiple myeloma (MM) in last two decades by using proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), monoclonal antibodies, and autologous stem cell transplantation (ASCT). With the associated improvement of overall survival, cumulative exposure to these agents have led to an increased incidence of secondary malignancies. Therapy-related myeloid neoplasms are more frequent than therapy-related B-cell acute lymphoblastic leukemia (t-B-ALL). We describe four patients who developed t-B-ALL following treatment for MM. All had received novel agents, three had lenalidomide maintenance, and two had undergone ASCT. Latency from MM diagnosis to t-B-ALL ranged from 3 to 7 years. Age ranged from 57-63 years with pancytopenia being the presentation. Bone marrow aspirates revealed Myeloperoxidase negative blasts with B-lineage immunophenotype. Cytogenetic and molecular findings were variable. At B-ALL diagnosis, clonal plasma cells or monoclonal band were absent, supporting clonal independence. Patients were treated with vincristine, anthracycline, and steroid-based regimens and achieved measurable residual disease negativity in two patients, however, only one patient alive at 21 months of follow-up and the remaining three succumbing within seven months of diagnosis. Therapy-related B-ALL is a rare but aggressive secondary malignancy in MM, commonly detected when presented with cytopenias. Prognosis of this entity is poor, in comparision to de novo B-ALL, underscoring the need for vigilant clinical follow-up, an urgent need to identify factors that predict the development of therapy-related malignancies and exploration of tailored therapeutic strategies.