Characteristics of Patients Presenting with Secondary Myelodysplastic Syndrome During Treatment with Lenalidomide for Relapsed/Refractory Multiple Myeloma: 5q Deletions Can Be Observed
Authors: Goswami Rashmi S. , Barth David , Masih-Khan Esther , Sun Haowei (Linda) , Mathew Manoj , Chen Christine , Trudel Suzanne , Kamel-Reid Suzanne , Reece Donna E. 
Published: October 2019

Abstract
Abstract 1876
Multiple myeloma (MM) is a neoplastic process involving plasma cells and the second most common hematologic malignancy after lymphoma. The relative survival rates for MM have been increasing over the last three decades, from 26% in the 1970s to 35% in recent years, due to the introduction of autologous stem cell transplantation (ASCT), and more recently, the introduction of novel agents. Among patients (pts) diagnosed with MM between 1997 and 2006, those who received at least one of the novel agents thalidomide, lenalidomide and bortezomib had double the median survival compared to those who did not receive any of these treatments (Kumar SK, Blood, 2008). Given that improvements are being made in the survival of myeloma pts, they may be more prone treatment-related complications, including treatment-related myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML). Herein we report seven cases of secondary MDS occurring in MM pts during treatment with lenalidomide-based (len-based) therapy for relapsed/refractory (rel/ref) MM. The pts examined were diagnosed with MM between 2000 and 2006, and consisted of 5 males and 2 females, ranging from 56–79 years of age (median age: 69 years). Five of the seven pts had undergone ASCT whereas the remaining two pts were treated with oral alkylating agents (cyclophosphamide/prednisone or melphalan/dexamethasone) as first-line treatment; one pt received another ASCT as second-line therapy. All pts received len-based regimens as second, third, or fourth-line therapy. The median time to development of MDS after diagnosis of MM was 70.5 months (range: 43.7 to 115.3 months). Of the pts that received ASCT as part of first-line therapy, the median time to development of MDS was 49.9 months (range: 35.6 to 76.1 months) post ASCT, while the median time to development of MDS after initiation of len-based treatment was 19.2 months (range: 1.1 to 33.8 months). All pts presented with decreasing blood counts at the time of MDS diagnosis; at this time the median hemoglobin level was 94 g/L (range 67–107 g/L), ANC 1.7 × 109/L (range 0.9–8.2 × 109/L) and platelet count 62 × 109/L (range 11–148 × 109/L) and only 1 pt had circulating blast cells. Pathological examination of blood films, bone marrow aspirates and biopsies confirmed the presence of MDS in all pts (4 pts with refractory cytopenia with multilineage dysplasia, 2 of whom also had ringed sideroblasts, 2 pts with refractory cytopenia with unilineage dysplasia, and 1 pt with refractory anemia with excess blasts-II); three had concomitant MM in the marrow. Of interest, 3 pts with evidence of dysmegakaryopoiesis demonstrated the presence of hypolobated megakaryocytes, similar to that seen in 5q- syndrome. Conventional cytogenetics demonstrated complex karyotypes in 6 pts, and 4 had structural abnormalities of chromosome 5, with deletion of the long arm, including 2 of the 3 pts with megakaryocyte hypolobation. Four of the 7 pts also had abnormalities involving chromosome 7, including deletion of 7q. In addition, 2 pts had deletions of chromosome 17 including deletion of TP53 (17q13). Although len may be a simple bystander in the development of MDS in rel/ref MM pts previously treated with alkylating agents, the observation of chromosome 5 abnormalities, including 5q deletion, is of note. Therefore, despite its established efficacy in the treatment of MDS, as well as of MM, len may not be able to protect against the development of MDS in pts previously treated with alkylating agents. As in other malignancies in which prolonged survival has been achieved, the increased life span of MM pts mandates monitoring for late complications of therapy. A progressive decrease in peripheral blood counts during treatment with len-based regimens warrants consideration of secondary MDS.

Disclosures:
Chen: Celgene Corporation: Consultancy, Honoraria, Research Funding. Trudel:Celgene: Honoraria. Reece:Celgene: Honoraria, Research Funding.