Document Type

Conference Proceeding

Publication Date

5-2-2025

Abstract

Introduction Autologous stem cell transplantation followed by maintenance with Lenalidomide has improved the overall survival and progression free survival in patients with Multiple Myeloma. However, maintenance therapy with Lenalidomide can increase the risk of several hematological adverse events including secondary B cell lymphoblastic leukemia. We present a case of 61 year old female who was previously treated for multiple myeloma and on maintenance Lenalidomide developed B lymphoblastic leukemia/lymphoma. Case presentation A 61 year old female initially presented with left sided hip pain and lower back pain in 2018.Chest X ray revealed mass like opacity in the left upper lobe and erosions of the left posterior aspect of the 6th rib which was confirmed on CT scan. Biopsy of the lesion showed plasma cell neoplasm. Further, flow cytometry was positive for lambda restricted plasma cell population. Monoclonal gammopathy evaluation showed an IgG lambda monoclonal protein measuring 4.1g/dl and elevated free lambda level of 55.26 mg/dl. Bone marrow biopsy showed bone marrow involvement by plasma cell myeloma with 20-30% marrow cellularity. She was treated with 4 cycles of chemotherapy with Lenalidomide, Carfilzomib and Dexamethasone as per protocol with concurrent Zoledronic acid. She showed complete response with normalization of her free lambda level and marked improvement in her monoclonal protein that became unmeasurable.She had a follow up biopsy in 2019 which showed no evidence of plasma cell myeloma. She underwent autologous bone marrow transplant after receiving Melphalan 200mg/m2. She was then started on maintenance Lenalidomide 10 mg 21 days on and 7 days off with monthly Zoledronic acid. She presented in December 2024 with worsening fatigue along with easy bruising, gingival bleeding and epistaxis. Complete blood counts showed anemia and thrombocytopenia. Peripheral smear showed granulocytic left shift with occasional circulating blasts with high suspicion for myeloid neoplasm. Bone marrow biopsy in January 2025 confirmed B lymphoblastic leukemia/lymphoma. Flow cytometry revealed a predominant B lymphoblastic leukemia/lymphoma. She is planned to get an induction chemotherapy with mini hyper CVD (Cyclophosphamide, Vincristine, methotrexate, Cytarabine and dexamethasone) with Intozumab, Ozogamicin and Rituxan every 21 days along with intrathecal chemotherapy. Discussion Incidence of therapy related secondary ALL is very low. It constitutes only 1.9 to 9 %of all the patients with hematological second primary malignancies. Some of the properties of Lenalidomide contribute to secondary B ALL. Lenalidomide binds to cereblon protein which is a part of E 3 ubiquitin ligase complex which takes part in repairing damaged DNA. Binding of Lenalidomide to cereblon protein downgrades transcription factors which are involved in the development of B cells leading to the clonal expansion of B cells. Some of the other risk factors include conditioning with Melphalan , patients age and length of survival contribute to the increased risk of secondary B ALL, making it multifactorial. Further studies are necessary to understand the complexity of this mechanism. This underscores the importance of close follow up of the patients on long term Lenalidomide, particularly for any secondary malignancies and educating the patients about potential adverse events.

Comments

American College of Physicians Michigan Chapter and Society of Hospital Medicine Michigan Chapter 2025 Resident and Medical Student Day, May 2, 2025, Troy, MI

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