Randomized multicenter phase II study of pomalidomide, cyclophosphamide, and dexamethasone in relapsed refractory myeloma
Mené sur 70 patients atteints d'un myélome multiple récidivant réfractaire, cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse globale, et la toxicité de l'ajout de cyclophosphamide à un traitement combinant pomalidomide et dexaméthasone à faibles doses
Pomalidomide dexamethasone and cyclophosphamide (PomCyDex) results in a higher overall response rate than pomalidomide and dexamethasone. PomCyDex is an effective, all oral regimen for refractory myeloma patients. Pomalidomide and low dose dexamethasone (PomDex) is standard treatment for lenalidomide refractory myeloma patients who have received more than 2 prior therapies. We aimed to assess the safety and efficacy of the addition of oral weekly cyclophosphamide to standard PomDex. We first performed a dose escalation phase I study to determine the recommended phase II dose of cyclophosphamide in combination with PomDex (arm A). A randomized, multicenter phase II study followed, enrolling patients with lenalidomide refractory myeloma. Patients were randomized (1:1) to receive pomalidomide 4 mg on days 1-21 of a 28 days cycle in combination with weekly dexamethasone (arm B) or PomDex with cyclophosphamide 400 mg orally on days 1,8,15 (arm C). The primary endpoint was the overall response rate (ORR). Eighty patients were enrolled (ten in the phase I, and 70 randomized in the phase II: 36 to arm B and 34 to arm C). The ORR was 38.9% (95% CI 23-54.8%) and 64.7% (95% CI 48.6-80.8) for arm B and C, respectively (p=0.035). As of June 2015, 62 of the 70 randomized patients had progressed. The median progression free survival (PFS) was 4.4 months (95% CI 2.3-5.7) and 9.5 months (95% CI 4.6-14) for arm B and C, respectively (p=0.106). Toxicity was predominantly hematologic in nature but was not statistically higher in arm C. The combination of PomCyDex results in a superior ORR and PFS as compared to PomDex in patients with lenalidomide refractory multiple myeloma. The study is registered at www.clinicaltrials.gov as NCT01432600.