Thalidomide therapy for myelofibrosis with myeloid metaplasia

Abstract

BACKGROUNDThalidomide is a putative antiangiogenesis agent with activity in several hematologic malignancies.METHODSForty‐four patients who had myelofibrosis with myeloid metaplasia received treatment with thalidomide in a Phase II clinical trial at a dose of 200 mg daily with escalation by 200 mg weekly until the best tolerated dose (maximum, 800 mg) was reached.RESULTSSeventeen of 41 evaluable patients (41%) who received treatment for at least 15 days had a response. A complete response (without reversal of bone marrow fibrosis) was achieved in 4 patients (10%), a partial response was achieved in 4 patients (10%), and hematologic improvements in anemia, thrombopenia, and/or splenomegaly were observed in 9 patients (21%). Improvements in anemia occurred in 7 of 35 patients (20%) with hemoglobin levels <10.0 g/dL, and improvements in thrombopenia occurred in 5 of 24 patients (21%) with platelet counts <100 × 109/L. Five of 24 patients (21%) became transfusion‐independent. Major or minor regression of splenomegaly was noted in 9 of 29 evaluable patients (31%), and complete regression was noted in 5 patients. Responders had a lower baseline median vascular endothelial growth factor levels (77.9 pg/mL vs. 97.7 pg/mL; P <.01) and higher median basis fibroblast growth factor levels (60.8 pg/mL vs. 37.4 pg/mL; P <.01) compared with nonresponders. Nine patients (22%) had deterioration that was attributed to thalidomide (resolved after withdrawal) with either progressive cytopenias or excessive proliferation. Two patients developed Grade 3 neutropenia with recovery and resumed therapy with dose reductions, and both later achieved a complete response. Dose‐related toxicities included fatigue (50%), constipation (48%), rash or pruritis (37%), sedation (35%), peripheral edema (29%), tremors (23%), peripheral neuropathy (22%), and orthostasis (16%).CONCLUSIONSThalidomide warrants further evaluation in patients with MMM, particularly in combination regimens, along with the investigation of newer analogs. Cancer 2006. © 2006 American Cancer Society.

Comparison of thalidomide and lenalidomide as therapy for myelofibrosis

“…The most common thalidomide side effects were neuropathy, rash, and fatigue, as previously reported. 2 In the lenalidomide single-agent group fatigue was also commonly reported but not in the lenalidomide plus prednisone group, probably because of prednisone use. Interestingly, rash was seen in the lenalidomide plus prednisone group later in the course of therapy when patients were off prednisone.…”

“…2,3 However, different studies used different response criteria; therefore, IWG established a set of clinically relevant response criteria several years ago, 4 now used in almost all MF studies. Reassessing our experience with IMiDs in MF we found the combination of lenalidomide plus prednisone to be possibly more effective (particularly important aspect is significantly longer response duration) and safer than single-agent thalidomide or lenalidomide.…”

“…1 Thalidomide and lenalidomide are 2 immunomodulatory agents (IMiDs) with clinical activity in a subset of patients with MF, including improvements in anemia, thrombocytopenia, and splenomegaly, thought to be because of their effect on BM environment. 2,3 In 2006, the International Working Group (IWG) for Myelofibrosis Treatment and Research proposed consensus criteria for evaluation of treatment response in patients with MF. 4 Although now in widespread use, the IWG criteria have not been used in previous trials of single-agent thalidomide and lenalidomide in MF.…”

Myeloproliferative neoplasms: A decade of discoveries and treatment advances

“…2). First-line drugs of choice in such patients are hydroxyurea for symptomatic splenomegaly [125], androgens preparations [126], prednisone [126], danazol [127], thalidomide 6 prednisone [128][129][130] or lenalidomide 6 prednisone [131,132] for symptomatic anemia, splenectomy (or splenic radiotherapy for nonsurgical candidates) for splenomegaly that is resistant to conventional drug therapy [133], involved field radiotherapy for nonhepatosplenic EMH might and ruxolitinib for severe constitutional symptoms that are resistant to hydroxyurea therapy [133].…”

Mini-dose of thalidomide for treatment of primary myelofibrosis. Report of a case with complete reversal of bone marrow fibrosis and splenomegaly

“…Thalidomide which down-regulates cytokine release involved in fibrosis and angiogenesis (VEGF, TGFbeta, beta-FGF, PDGF), has been used with variable responses in the treatment of MF [2][3][4][5][6] . Thalidomide induced improvement in disease-associated anemia and thrombocytopenia and in some cases decreased splenomegaly.…”