Thalidomide therapy for myelofibrosis with myeloid metaplasia

Deborah A. Thomas, Francis J. Giles, Maher Albitar, Jorge E. Cortes, Srdan Verstovsek, Stefan Faderl, Susan M. O'Brien, Guillermo Garcia-Manero, Michael J. Keating, Sherry Pierce, Jerome Zeldis, Hagop M. Kantarjian

Research output: Contribution to journalArticle

Abstract

BACKGROUND. Thalidomide is a putative antiangiogenesis agent with activity in several hematologic malignancies. METHODS. Forty-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. RESULTS. Seventeen 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 orthotasis (16%). CONCLUSIONS. Thalidomide warrants further evaluation in patients with MMM, particularly in combination regimens, along with the investigation of newer analogs.

Original languageEnglish (US)
Pages (from-to)1974-1984
Number of pages11
JournalCancer
Volume106
Issue number9
DOIs
StatePublished - May 1 2006
Externally publishedYes

Fingerprint

Primary Myelofibrosis
Thalidomide
Therapeutics
Splenomegaly
Thrombocytopenia
Anemia
Phase II Clinical Trials
Maximum Tolerated Dose
Fibroblast Growth Factors
Peripheral Nervous System Diseases
Tremor
Hematologic Neoplasms
Constipation
Pruritus
Exanthema
Neutropenia
Platelet Count
Vascular Endothelial Growth Factor A
Fatigue
Edema

Keywords

  • Agnogenic myaloid metaplasia
  • Basic fibroblast growth factor
  • Myelofibrosis
  • Thalidomide
  • Tumor necrosis factor α
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Thomas, D. A., Giles, F. J., Albitar, M., Cortes, J. E., Verstovsek, S., Faderl, S., ... Kantarjian, H. M. (2006). Thalidomide therapy for myelofibrosis with myeloid metaplasia. Cancer, 106(9), 1974-1984. https://doi.org/10.1002/cncr.21827

Thalidomide therapy for myelofibrosis with myeloid metaplasia. / Thomas, Deborah A.; Giles, Francis J.; Albitar, Maher; Cortes, Jorge E.; Verstovsek, Srdan; Faderl, Stefan; O'Brien, Susan M.; Garcia-Manero, Guillermo; Keating, Michael J.; Pierce, Sherry; Zeldis, Jerome; Kantarjian, Hagop M.

In: Cancer, Vol. 106, No. 9, 01.05.2006, p. 1974-1984.

Research output: Contribution to journalArticle

Thomas, DA, Giles, FJ, Albitar, M, Cortes, JE, Verstovsek, S, Faderl, S, O'Brien, SM, Garcia-Manero, G, Keating, MJ, Pierce, S, Zeldis, J & Kantarjian, HM 2006, 'Thalidomide therapy for myelofibrosis with myeloid metaplasia', Cancer, vol. 106, no. 9, pp. 1974-1984. https://doi.org/10.1002/cncr.21827
Thomas DA, Giles FJ, Albitar M, Cortes JE, Verstovsek S, Faderl S et al. Thalidomide therapy for myelofibrosis with myeloid metaplasia. Cancer. 2006 May 1;106(9):1974-1984. https://doi.org/10.1002/cncr.21827
Thomas, Deborah A. ; Giles, Francis J. ; Albitar, Maher ; Cortes, Jorge E. ; Verstovsek, Srdan ; Faderl, Stefan ; O'Brien, Susan M. ; Garcia-Manero, Guillermo ; Keating, Michael J. ; Pierce, Sherry ; Zeldis, Jerome ; Kantarjian, Hagop M. / Thalidomide therapy for myelofibrosis with myeloid metaplasia. In: Cancer. 2006 ; Vol. 106, No. 9. pp. 1974-1984.
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AU - Faderl, Stefan

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N2 - BACKGROUND. Thalidomide is a putative antiangiogenesis agent with activity in several hematologic malignancies. METHODS. Forty-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. RESULTS. Seventeen 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 orthotasis (16%). CONCLUSIONS. Thalidomide warrants further evaluation in patients with MMM, particularly in combination regimens, along with the investigation of newer analogs.

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KW - Agnogenic myaloid metaplasia

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KW - Myelofibrosis

KW - Thalidomide

KW - Tumor necrosis factor α

KW - Vascular endothelial growth factor

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