Durable Long-Term Responses in Patients with Myelodysplastic Syndromes Treated with Lenalidomide

doi:10.3816/CLM.2009.n.053

Clinical Lymphoma and Myeloma

Volume 9, Issue 3, June 2009, Pages E10-E13

https://doi.org/10.3816/CLM.2009.n.053 Get rights and content

Abstract

Lenalidomide has proven efficacy and safety and has been shown to reduce transfusion requirements and reverse cytogenetic abnormalities in lower-risk myelodysplastic syndromes (MDS). However, long-term follow-up data have not yet been reported. Here, we describe 6 patients with International Prognostic Scoring System low- or intermediate-1—risk MDS who began lenalidomide therapy between April 2002 and June 2003 as part of the MDS-001 study and who have maintained long-term therapy. Five of these patients had an ongoing requirement for red blood cell transfusions despite previous treatment with recombinant erythropoietin. One patient began lenalidomide therapy because of progressive and symptomatic anemia. To date, all patients maintained long-term transfusion independence (over 4.5 years) while receiving oral lenalidomide therapy, including 5 patients who remain on therapy. Sustained erythroid response was reported despite persistence of the deletion 5q [del(5q)] abnormality in 3 of the 4 patients with del(5q) at study entry. Side effects were largely predictable and manageable. The favorable outcomes presented here show that lenalidomide can induce durable erythroid responses with sustained transfusion independence that can exceed 6 years in patients with lower-risk MDS.

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Interestingly, 83% of patients with a chromosome 5q31.1 deletion responded to lenalidomide as compared with 57% with a normal karyotype and 12% with other karyotypic abnormalities (P = .007) (List et al., 2005). Six patients with IPSS low- or intermediate-1-risk MDS from MDS-001 trial received maintenance therapy resulting in long-term TI (over 4.5 years), with 4 patients having deletion 5q (Kurtin & List, 2009). The phase II MDS-003 study further investigated the efficacy of lenalidomide in MDS patients with 5q31 deletion.
Immunomodulatory drugs (IMiDs) have been used in hematologic malignancies for the last decade. However, the mechanism of action of IMiDs is largely unknown. Here we provide a comprehensive overview of pivotal studies, recent advances in the application of IMiDs in cancer as well as their effects on hematopoietic stem cells including the risk of secondary malignancies. IMiDs have a well-established role as first-line therapy for patients with newly diagnosed and relapsed/refractory multiple myeloma (MM). Variant combinations of IMiDs with other chemotherapy reagents show promising outcomes in MM. Recent concerns on increased rate of secondary cancer in MM patients treated with maintenance lenalidomide were raised. But analysis of maintenance studies showed that the benefit of maintenance outweighs the risk of secondary cancers in MM. IMiDs also show efficacy in myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), Non-Hodgkin's lymphoma (NHL) and myelofibrosis (MF), but not in solid tumors. The major adverse effects are venous thromboembolism, neuropathy and cytopenias. IMiDs induce expansion and self-renewal of CD34+ hematopoietic progenitors and inhibit lineage maturation/differentiation by affecting critical transcription factors which might contribute to myelosuppression effect of IMiDs.
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Despite the impressive remissions seen in many of these patients, over time lenalidomide resistance may develop owing to recurrence or expansion of the del(5q) clone; however, this has not been shown in a prospective study with appropriate controls.16 It should also be noted that patients with MDS and del(5q) abnormality who are treated with lenalidomide can remain transfusion-independent for extended periods even after discontinuation of treatment and, in some cases, despite persistence or reoccurrence of the del(5q) clone.17,18 Lenalidomide is generally well tolerated; however, it can cause grade 3 or 4 neutropenia and thrombocytopenia, which require intervention.15
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Case ReportDurable Long-Term Responses in Patients with Myelodysplastic Syndromes Treated with Lenalidomide

Abstract

Blood

Blood

Blood

Time-dependent prognostic scoring system for predicting survival and leukemia evolution in myelodysplastic syndromes

J Clin Oncol

Case Report
Durable Long-Term Responses in Patients with Myelodysplastic Syndromes Treated with Lenalidomide