J Clin Oncol 31, 2013 (suppl; abstr 8584)
Paul Gerard Guy Richardson, Craig C. Hofmeister, David Samuel DiCapua Siegel, Sagar Lonial, Jacob Laubach, Yvonne Adeduni Efebera, David H. Vesole, Ajay K. Nooka, Jacalyn Rosenblatt, Noopur S. Raje, Mohamed H. Zaki, Ye Hua, Sheetal Shah, Jianming Wang, Kenneth Carl Anderson; Dana-Farber Cancer Institute, Boston, MA; Department of Internal Medicine, Division of Hematology, The Ohio State University, Columbus, OH; John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ; Emory University School of Medicine, Atlanta, GA; Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA; Division of BMT, Emory University, Winship Cancer Institute - Hematology and Medical Oncology, Atlanta, GA; Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, MA; Massachusetts General Hospital, Boston, MA; Celgene Corporation, Summit, NJ
Background: Combinations of lenalidomide (LEN), bortezomib (BORT), and dexamethasone (DEX) have demonstrated preclinical and clinical activity in patients (pts) with multiple myeloma. Pomalidomide with low-dose DEX (LoDEX) has demonstrated efficacy in RRMM pts treated with prior LEN and BORT. MM-005 was designed to identify the optimal PVD dose for a phase 3 trial comparing PVD vs BORT + LoDEX (VD) in RRMM (MM-007).
Methods: Eligible pts had RRMM with 1-4 prior therapies including ≥ 2 consecutive cycles of LEN and a proteasome inhibitor. Pts must have been refractory to LEN (progressive disease [PD] during or within 60 days of LEN treatment), but not refractory to BORT (at 1.3 mg/m2 twice-weekly). The maximum tolerated dose (MTD) was determined using a 3 + 3 design in 5 cohorts. Each cohort received 21-day cycles of POM 1-4mg/day on D1-14; BORT 1-1.3mg/m2on D1, 4, 8, 11; and LoDEX 20mg/day on D1-2, 4-5, 8-9, 11-12. An expansion cohort was enrolled at the MTD. Treatment was continued until PD or unacceptable toxicity. Dose-limiting toxicities (DLTs) were assessed during cycle 1. The primary endpoint was MTD; secondary endpoints were safety, overall response rate (ORR; ≥ partial response), duration of response, and time to response (TTR).
Results: As of Dec 31, 2012, 21 pts were enrolled (3 pts per escalating dose cohort; 6 in the expansion cohort). Median age was 57 years (36-75). All were LEN-refractory and had prior BORT. No DLTs were observed at any dose level. The most common grade 3/4 adverse events (AEs) were neutropenia (32%) and thrombocytopenia (21%). With thromboprophylaxis, no deep vein thrombosis was observed. 17 pts remain on study and no pts have discontinued treatment due to AE. Thus far, the ORR was 72% (n = 18 evaluable) and responses were rapid (median TTR, 2 cycles).
Conclusions: PVD was well-tolerated in RRMM with no DLTs and no discontinuations due to AE to date. PVD has promising activity with a current ORR of 72%. The maximum planned dose of POM 4mg/day on D1-14; BORT 1.3mg/m2 on D1, 4, 8, and 11; and DEX 20mg on D1-2, 4-5, 8-9, 11-12 of a 21-day cycle has now been incorporated into the MM-007 phase III trial comparing PVD with VD in RRMM pts (N = 782 planned).
Clinical trial information: NCT01497093