A Phase I Study of Ruxolitinib, Lenalidomide, and Steroids for Patients with Relapsed/Refractory Multiple Myeloma
| Autor: | Armando Sanchez, Robert Vescio, Shahrooz Eshaghian, Daisy Martinez, Tanya M. Spektor, James R. Berenson, Regina A. Swift, Robert A. Moss, Laura Stampleman, Jennifer To, Stephen Lim, Benjamin Eades, Matthew Ghermezi, Gary T. Schwartz, Carley Turner |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Oncology Male Cancer Research medicine.medical_specialty Ruxolitinib Dexamethasone 03 medical and health sciences 0302 clinical medicine Refractory Internal medicine Antineoplastic Combined Chemotherapy Protocols Nitriles medicine Humans Lenalidomide Multiple myeloma Aged Aged 80 and over Dose-Response Relationship Drug business.industry Janus Kinase 1 Janus Kinase 2 Middle Aged medicine.disease Survival Rate 030104 developmental biology Pyrimidines Methylprednisolone Drug Resistance Neoplasm 030220 oncology & carcinogenesis Proteasome inhibitor Pyrazoles Female Neoplasm Recurrence Local business Multiple Myeloma Progressive disease medicine.drug |
| Zdroj: | Clinical cancer research : an official journal of the American Association for Cancer Research. 26(10) |
| ISSN: | 1557-3265 |
| Popis: | Purpose: Ruxolitinib with lenalidomide and dexamethasone shows antimyeloma effects in vitro and in vivo. MUC1 leads to lenalidomide resistance in multiple myeloma cells, and ruxolitinib blocks its expression. Thus, ruxolitinib may restore sensitivity to lenalidomide. Therefore, a phase I trial was conducted to determine the safety and efficacy of ruxolitinib with lenalidomide and methylprednisolone for patients with relapsed/refractory multiple myeloma (RRMM) who had been treated with lenalidomide/steroids and a proteasome inhibitor and showed progressive disease at study entry. Patients and Methods: A traditional 3+3 dose escalation design was used to enroll subjects in four cohorts with planned total enrollment of 28 patients. Subjects received ruxolitinib twice daily, lenalidomide daily on days 1–21 of a 28-day cycle, and methylprednisolone orally every other day. Primary endpoints were safety, clinical benefit rate (CBR), and overall response rate (ORR). Results: Twenty-eight patients were enrolled. The median age was 67 years and received a median of six prior treatments including lenalidomide and steroids to which 93% were refractory. No dose-limiting toxicities occurred. The CBR and ORR were 46% and 38%, respectively. All 12 responding patients were refractory to lenalidomide. Grade 3 or grade 4 adverse events (AE) included anemia (18%), thrombocytopenia (14%), and lymphopenia (14%). Most common serious AEs included sepsis (11%) and pneumonia (11%). Conclusions: This phase I trial demonstrates that a JAK inhibitor, ruxolitinib, can overcome refractoriness to lenalidomide and steroids for patients with RRMM. These results represent a promising novel therapeutic approach for treating multiple myeloma (ClinicalTrials.gov number, NCT03110822). |
| Databáze: | OpenAIRE |
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