Durable response to lenalidomide in a patient with myelodysplastic syndrome associated with isolated 5q deletion and JAK2 V617F mutation despite discontinuation of treatment

Abstract

Abstract. Loss of a section of the long arm of chromosome 5, as a sole cytogenetic abnormality, characterizes a rare type of myelodysplastic syndrome [del(5q) MDS] and the co-existence of the JAK2 V617F mutation occurs in a small subset of these cases. Patients with isolated del(5q) MDS have a relatively favorable prognosis, with transformation to acute myeloid leukemia occurring in <10%, and their disease responds well to lenalidomide. However the optimal therapeutic approach for patients with del(5q) MDS in coexistence with the JAK2 V617F mutation, which is common to myeloproliferative neoplasms, remains to be elucidated. The present study reports a 77-year-old, transfusion-dependent female patient diagnosed with del(5q) MDS and a concomitant JAK2 V617F mutation. The patient was started on 10 mg lenalidomide daily for 21 days in a 28 day-cycle and within the first month of treatment, the patient became transfusion-independent. The only toxicity observed was grade 3 neutropenia, which was managed with transient treatment discontinuation and dose reduction on restart (5 mg). The patient achieved a complete cytogenetic and molecular response (normal karyotype and undetected JAK2 V617F mutation) within 6 months of treatment. However, 12 months post treatment initiation and while on hematological, cytogenetic and molecular response, the patient was unwilling to continue on treatment and lenalidomide was discontinued. The patient remains in hematological response, which lasts for >5 years despite treatment discontinuation. The present case highlights the coexistence of the JAK2 V617F mutation in del(5q) MDS and suggests that lenalidomide treatment is beneficial and effective for these patients, leading to complete hematological, cytogenetic and molecular response. Hematological response may be sustained for long periods of time, even following the discontinuation of the treatment.

Concomitant chromosome 5q-deletion and JAK2V617F mutation present with myelodysplastic and myeloproliferative overlap features

“…As previously reported in patients with a concomitant del(5q) and JAK2 V617F mutation, the hallmark of our patients' presentations include anemia and marked thrombocytosis [10]. A majority of patients are also transfusion dependent [10,13,14]. While this appears similar to MPNs, the transfusion-dependent anemia and thrombocytosis does not typically respond to erythropoietin and hydroxyurea respectively [14][15][16].…”

“…While this appears similar to MPNs, the transfusion-dependent anemia and thrombocytosis does not typically respond to erythropoietin and hydroxyurea respectively [14][15][16]. In some cases with a del (5q) and JAK2 V617F mutation, platelet and leukocyte counts did normalize with a regimen of interferon-alpha, aspirin and hydroxyurea, but this did not improve the anemia [10,13]. This behavior, as well as the response to lenalidomide, is more similar to an MDS-type clinical course.…”

“…This behavior, as well as the response to lenalidomide, is more similar to an MDS-type clinical course. In most case reports, treatment with lenalidomide obliterates all cellular clones with del(5q) and in some cases reduction in JAK2 V617F positive clone was observed [13][14][15][16]. For example, a complete molecular response occurred in one patient with undetectable JAK2 V617F mutation by quantitative real time polymerase reaction after 9 months of lenalidomide treatment compared to baseline JAK2 V617F allele burden of 26.28% [14].…”

Transfusion independence after lenalidomide discontinuation in patients with del(5q) myelodysplastic syndrome: a HARMONY Alliance study

“…Some retrospective case reports or series involving a small number of patients have shown that most RBC-TI patients who stopped LEN maintained the hematological response. This nding was more evident in patients who had received at least 6-12 months of LEN and who were RBC-TI and had achieved a CCyR (20)(21)(22).…”