Secondary B-acute lymphoblastic leukemia following lenalidomide maintenance in multiple myeloma

Following the advent of immunomodulatory agents (IMiDs) in the treatment of multiple myeloma (MM), the progression-free survival has improved significantly. This has also led to increased recognition of second primary malignancy (SPM), like myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) among MM patients treated with IMiDs, especially lenalidomide. The occurrence of acute lymphoblastic leukemia (ALL) post lenalidomide therapy is rare. A 61 years old male with kappa light chain MM was treated with lenalidomide-dexamethasone induction for 6 cycles, followed by lenalidomide maintenance for 2 years, and achieved very good partial response. 7 months after stopping therapy, he developed severe thrombocytopenia. Bone marrow examination at this point revealed B-ALL with 4% clonal plasma cells. A diagnosis of secondary B-ALL, related to lenalidomide, was considered. Increased incidence of SPM is recognized in MM among lenalidomide-treated patients. This is especially the case if they have been given sequential or concomitant oral melphalan. An increased incidence of SPM is also seen post autotransplant using high-dose melphalan. Usually, hematological SPMs seen in this scenario are myeloid malignancies like MDS/AML. There are emerging data, in the form of case reports and case series, of ALL occurrence as a second primary. Our case report adds credence to this observation. Our case also highlights the potential of lenalidomide monotherapy to cause SPM, in the absence of alkylating agents. Clinicians should recognize the rare possibility of ALL among patients with MM treated with lenalidomide for a prolonged duration.