A phase 1 study of ruxolitinib, steroids and lenalidomide for relapsed/refractory multiple myeloma patients.

Autor: Berenson JR; Berenson Cancer Center, West Hollywood, Los Angeles, California, USA.; Oncotherapeutics, West Hollywood, Los Angeles, California, USA.; Institute for Myeloma and Bone Cancer Research, West Hollywood, Los Angeles, California, USA., Kim C; Oncotherapeutics, West Hollywood, Los Angeles, California, USA., Bujarski S; Berenson Cancer Center, West Hollywood, Los Angeles, California, USA., To J; Oncotherapeutics, West Hollywood, Los Angeles, California, USA., Spektor TM; Oncotherapeutics, West Hollywood, Los Angeles, California, USA., Martinez D; Oncotherapeutics, West Hollywood, Los Angeles, California, USA., Turner C; Oncotherapeutics, West Hollywood, Los Angeles, California, USA., Ghermezi M; Oncotherapeutics, West Hollywood, Los Angeles, California, USA., Eades BM; Berenson Cancer Center, West Hollywood, Los Angeles, California, USA., Swift RA; Berenson Cancer Center, West Hollywood, Los Angeles, California, USA., Schwartz G; Berenson Cancer Center, West Hollywood, Los Angeles, California, USA., Eshaghian S; Compassionate Care Research Group, Fountain Valley, Los Angeles, California, USA., Moss RA; F.A.C.P., Inc, Fountain Valley, Los Angeles, California, USA., Lim S; Cedars-Sinai Medical Center, Los Angeles, California, USA., Vescio R; Cedars-Sinai Medical Center, Los Angeles, California, USA.
Jazyk: angličtina
Zdroj: Hematological oncology [Hematol Oncol] 2022 Dec; Vol. 40 (5), pp. 906-913. Date of Electronic Publication: 2022 Aug 14.
DOI: 10.1002/hon.3066
Abstrakt: Ruxolitinib with lenalidomide and dexamethasone shows anti-myeloma effects in vitro and in vivo. MUC1 leads to lenalidomide resistance in multiple myeloma (MM) cells, and ruxolitinib blocks its expression. Thus, ruxolitinib may restore sensitivity to lenalidomide. A phase I trial was conducted to determine the safety and efficacy of ruxolitinib with lenalidomide and methylprednisolone for patients with relapsed/refractory (RR)MM who had been treated with lenalidomide, steroids and a proteasome inhibitor and showed progressive disease at study entry. A traditional 3 + 3 dose escalation design was used to enroll subjects in four cohorts. 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). Forty-nine patients were enrolled. The median age was 64 years and they had received a median of six prior treatments including lenalidomide and steroids to which 94% were refractory. No dose limiting toxicities occurred. The CBR and ORR were 49% and 36%, respectively. All responding patients were refractory to lenalidomide. Grade 3 or 4 adverse events (AEs) included anemia (17%), decreased lymphocyte count (15%), and hypophosphatemia (10%). Most common serious AEs included sepsis (9.8%) and pneumonia (7.8%). 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 MM. NCT03110822.
(© 2022 John Wiley & Sons Ltd.)
Databáze: MEDLINE
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