Lenalidomide plus prednisone results in durable clinical, histopathologic, and molecular responses in patients with myelofibrosis.

Abstract

PURPOSE:

To investigate the safety and efficacy of the combination of lenalidomide and prednisone in patients with myelofibrosis (MF).

PATIENTS AND METHODS:

Forty patients with MF were treated. Therapy consisted of lenalidomide 10 mg/d (5 mg/d if baseline platelet count < 100 x 10(9)/L) on days 1 through 21 of a 28-day cycle for six cycles, in combination with prednisone 30 mg/d orally during cycle 1, 15 mg/d during cycle 2, and 15 mg/d every other day during cycle 3. Lenalidomide therapy was continued indefinitely in patients exhibiting clinical benefit.

RESULTS:

The median follow-up was 22 months (range, 6 to 27). Responses were recorded in 12 patients (30%) and are ongoing in 10 (25%). The median time to response was 12 weeks (range, 2 to 32). According to the International Working Group for Myelofibrosis Research and Treatment consensus criteria, three patients (7.5%) had partial response and nine patients (22.5%) had clinical improvement durable for a median of 18 months (range, 3.5 to 24+). Overall response rates were 30% for anemia and 42% for splenomegaly. Moreover, 10 of 11 assessable responders who started therapy with reticulin fibrosis grade 4 experienced reductions to at least a score of 2. All eight JAK2(V617F)-positive responders experienced a reduction of the baseline mutant allele burden, which was greater than 50% in four, including one of whom the mutation became undetectable. Grade 3 to 4 hematologic adverse events included neutropenia (58%), anemia (42%), and thrombocytopenia (13%).

CONCLUSION:

The combination of lenalidomide and prednisone induces durable clinical, molecular, and pathologic responses in MF.

• Authors: Alfonso Quintás-Cardama, Hagop M Kantarjian, Taghi Manshouri, Deborah Thomas, Jorge Cortes, Farhad Ravandi, Guillermo Garcia-Manero, Alessandra Ferrajoli, Carlos Bueso-Ramos, Srdan Verstovsek
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 27 Issue 28 Pg. 4760-6 (Oct 01 2009) ISSN: 1527-7755 [Electronic] United States
• PMID: 19720904 (Publication Type: Clinical Trial, Phase II, Journal Article)

Chemical References

• Antineoplastic Agents
• Glucocorticoids
• Platelet-Derived Growth Factor
• Transforming Growth Factor beta
• Fibroblast Growth Factor 2
• Thalidomide
• JAK2 protein, human
• Janus Kinase 2
• Lenalidomide
• Prednisone

Topics

• Adult
• Aged
• Aged, 80 and over
• Anemia (chemically induced)
• Antineoplastic Agents (administration & dosage, therapeutic use)
• Drug Therapy, Combination
• Enzyme-Linked Immunosorbent Assay
• Female
• Fibroblast Growth Factor 2 (blood)
• Glucocorticoids (therapeutic use)
• Humans
• Janus Kinase 2 (genetics)
• Lenalidomide
• Male
• Middle Aged
• Mutation
• Neutropenia (chemically induced)
• Platelet-Derived Growth Factor (metabolism)
• Prednisone (therapeutic use)
• Primary Myelofibrosis (blood, drug therapy, genetics)
• Thalidomide (adverse effects, analogs & derivatives, therapeutic use)
• Thrombocytopenia (chemically induced)
• Transforming Growth Factor beta (blood)
• Treatment Outcome