Ruxolitinib in combination with Lenalidomide as therapy for patients with myelofibrosis
| Autor: | Naval Daver, Elias Jabbour, Gautam Borthakur, Xuemei Wang, Sherry Pierce, Naveen Pemmaraju, Lingsha Zhou, Kate J. Newberry, Koji Sasaki, Hagop M. Kantarjian, Jorge E. Cortes, Tapan M. Kadia, Srdan Verstovsek, Farhad Ravandi |
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| Rok vydání: | 2015 |
| Předmět: |
Adult
Male medicine.medical_specialty Ruxolitinib Bone marrow fibrosis Gastroenterology Palpable spleen Bone Marrow Internal medicine Antineoplastic Combined Chemotherapy Protocols Nitriles Humans Medicine Dosing Myelofibrosis Lenalidomide Aged Aged 80 and over Chromosome Aberrations Response rate (survey) business.industry Articles Hematology Janus Kinase 2 Middle Aged medicine.disease Thalidomide Surgery Clinical trial Pyrimidines Treatment Outcome Primary Myelofibrosis Mutation Pyrazoles Female business Follow-Up Studies medicine.drug |
| Zdroj: | Haematologica. |
| ISSN: | 1592-8721 0390-6078 |
| DOI: | 10.3324/haematol.2015.126821 |
| Popis: | Ruxolitinib and lenalidomide may target distinct clinical and pathological manifestations of myelofibrosis and prevent therapy-related worsening of blood cell counts. To determine the efficacy and safety of the combination in patients with myelofibrosis, patients were given 15 mg ruxolitinib orally twice daily in continuous 28-day cycles, plus 5 mg lenalidomide orally once daily on days 1-21. Thirty-one patients were treated, with a median followup of 28 months (range, 12 - 35+). Due to failure to meet the predetermined efficacy rules for treatment success the study was terminated early. Simultaneous administration of ruxolitinib and lenalidomide was difficult: 20 of the 23 dose interruptions occurred within the first 3 months of therapy. Lenalidomide was interrupted in all 20 cases. Fourteen patients (45%) were completely off lenalidomide within 3 months of initiation. Responses were noted in 17 patients (55%). The median time to response was 1.8 months (range, 0.4 - 31). All responses were International Working Group for Myelofibrosis Research and Treatment-defined clinical improvement in palpable spleen size. One spleen responder also met the criteria for clinical improvement in hemoglobin. The response rate was higher (73%) among patients who did not require early dose interruption than among those who required early interruption (45%). Improvements in bone marrow fibrosis and serial reductions in lactate dehydrogenase >50% were noted in 17% and 50% of evaluable responders, respectively. Alternate approaches such as sequential dosing need to be evaluated when considering novel combination strategies for myelofibrosis. This trial was registered with clinicaltrials.gov identifier: NCT01375140. |
| Databáze: | OpenAIRE |
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