Lenalidomide-Associated Secondary B-Lymphoblastic Leukemia/Lymphoma—A Unique Entity

Abstract

Objectives Autologous stem cell transplant with lenalidomide maintenance therapy has greatly improved the relapse-free and overall survival rates of patients with multiple myeloma but also has been associated with an increased risk of secondary B-lymphoblastic leukemia/lymphoma (B-ALL). Methods We report a comprehensive review of the clinicopathologic features of 2 patients with multiple myeloma who developed secondary B-ALL during lenalidomide maintenance. Results Our observations showed that the disease may initially present with subtle clinical, morphologic, and flow-cytometric findings. The flow cytometry findings in such cases may initially mimic an expansion of hematogones with minimal immunophenotypic variation. Both patients achieved complete remission of secondary B-ALL after standard chemotherapy; however, one patient continues to have minimal residual disease, and the other experienced relapse. Next-generation sequencing of the relapse specimen showed numerous, complex abnormalities, suggesting clonal evolution. Conclusions Our findings suggest the need for increased awareness and further study of this unique form of secondary B-ALL.

Therapy-related B-lymphoblastic leukemia after multiple myeloma

“…t-B-ALL is rare or under-recognized, with <50 reported cases to our knowledge individually or in small series, and additional cases described within larger analyses [ 30 , 31 ] Table 2 . A recent review describes a wide age range at diagnosis (range 33–82 years), with a median age of 61.5 years [15] ; our patients had a narrower age range of 51–76 years, and a similar median age of 64 years. The published time to development of t-B-ALL is also highly variable, with a range of 2–84 months, median 32.5 months [15] ; similarly, t-B-ALL developed after 23 – 88 months in our patients, with a median of 51.5 months.…”

“…We report our institution's experience with eight patients diagnosed with t-B-ALL or incipient t-B-ALL in the setting of therapy for MM, including lenalidomide maintenance therapy. While therapy-related malignancies in this setting are far more commonly myeloid neoplasms [13] , recent reports of t-B-ALL in the literature reflect increasing recognition of this entity [ 10 , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] ]. t-B-ALL is rare or under-recognized, with <50 reported cases to our knowledge individually or in small series, and additional cases described within larger analyses [ 30 , 31 ] Table 2 .…”

Secondary B-cell acute lymphoblastic leukaemia in a patient with multiple myeloma

“…Prior case series have described similar cases of B-ALL in the setting of prior ASCT and lenalidomide maintenance therapy 10–14. Within these series, patients often presented with asymptomatic pancytopenia after two or more years on maintenance therapy.…”

Treatment-Associated Acute Lymphoblastic Leukemia Following Autologous Hematopoietic Stem Cell Transplant and Lenalidomide Maintenance in Patients With Multiple Myeloma

“… 6 , 19 Another question that needs to be answered is whether lenalidomide has an association with masked hypodiploid ALL as this is associated with an extremely poor prognosis. 14 , 20 Masked hypodiploidy is a described phenomenon where hypodiploid cells (<43 chromosomes) appear hyperdiploid but are actually from the cells doubling the chromosomal content of their previously hypodiploid cells. 20 In addition, masked hypodiploidy is associated with a high rate of TP53 mutations which are associated with a poor response to therapy.…”