SP13 | SECONDARY ACUTE MEGAKARYOCYTIC LEUKEMIA IN A PATIENT WITH MULTIPLE MYELOMA ON MAINTENANCE THERAPY WITH LENALIDOMIDE AFTER AUTOLOGOUS BONE MARROW TRANSPLANT

Acute megakaryocytic leukemia (AMegL) is a rare and heterogeneous form of acute myeloid leukemia (AML), with increased frequency in children with Down syndrome. Here, we report a case of secondary AMegL in a patient with Multiple Myeloma (MM), who was undergoing maintenance therapy with lenalidomide after Autologous Bone Marrow Transplantation. A 64-year-old man was diagnosed with symptomatic MM IgG K, International Staging System (ISS) II in June 2019, with high risk due to TP53 mutation. He underwent induction therapy with the VTD regimen (bortezomib, thalidomide, and dexamethasone) for 6 cycles, followed by stem cell collection and autologous stem cell transplant with melphalan conditioning (200 mg/m²) on January 9, 2020, achieving a very good partial response (VGPR). Maintenance therapy with lenalidomide was initiated about 100 days post-transplant. In December 2021, during the 19th cycle of maintenance therapy, the patient developed thrombocytopenia, leading to the discontinuation of lenalidomide. Despite this, bone marrow evaluation showed plasma cell infiltration (8-10%), mild erythroid dysplasia, and reduced megakaryocytes. Cytogenetic analysis by FISH revealed CKS1B gene amplification in 10% of nuclei and trisomy 5 in 25% of nuclei. In March 2022, due to worsening thrombocytopenia and anemia, bone marrow examination revealed 22% blasts, low CD45 expression, and negativity for myeloid and lymphoid markers, except for CD4. High positivity for megakaryocyte antigens (CD61, CD41, CD42a, CD36, CD71, CD9) suggested AMegL. Cytogenetics showed a karyotype with 44 chromosomes, probable 5q deletion, monosomy of chromosome 18, and structural alteration of chromosome 19. The patient was started on Decitabine and Venetoclax therapy but developed sepsis due to Escherichia coli, leading to death. Secondary primary malignant neoplasms (PMS), including myelodysplastic syndrome (MDS) and AML, are known complications of lenalidomide treatment. However, the survival benefit of lenalidomide maintenance outweighs the risk of secondary malignancies, and it remains recommended in current guidelines. AMegL, a rare form of leukemia, requires further study to determine whether it is linked to pharmacological treatment, genomic instability, or the myeloma microenvironment. Close monitoring is essential for patients receiving lenalidomide to detect potential complications.