Saad Z. Usmani, MD
Levine Cancer Institute - Morehead
Charlotte, North Carolina, USA

SWOG 1211: A randomized phase I/II study of optimal induction therapy for newly diagnosed high-risk multiple myeloma (HRMM)

Abstract No: TPS8624

Background: The introduction of immunomodulatory agents and proteasome inhibitors, and advances in high dose therapy administration have made an impact on progression free survival (PFS) and overall survival (OS) for multiple myeloma (MM) patients in general, but patients with HRMM still have a poor long-term prognosis. Therefore, it is imperative to develop novel therapeutic regimens that will extend PFS and OS in this group. The SWOG 1211 is the first national and inter-group study targeting the HRMM population.

Methods: Eligibility and Trial Design: A randomized phase I/II trial was designed to evaluate the efficacy of incorporating novel agents into first line therapy for HRMM patients comparing lenalidomide, bortezomib and dexamethasone (RVD) with or without addition of elotuzumab (Elo). Eligible patients must have a documented history of HRMM defined by one or more of the following: Poor risk genomics defined by 70-gene model. Translocation (14;16), translocation (14;20) and/or deletion (17p) by florescent in-situ hybridization (FISH). Primary plasma cell leukemia. Serum LDH > 2 times normal levels. Objectives: Phase I: To determine the maximum tolerated dose (MTD) of RVD-Elo. Phase II: To assess whether incorporation of the novel agent Elo into treatment algorithm of HRMM will improve PFS. Statistical Considerations: The phase I study enrolled 6 DLT evaluable patients; no DLTs were observed. The phase II study is now open and will accrue 100 eligible patients (50 per arm). An additional 10 patients (5 per arm) will be accrued to account for ineligibility/patients withdrawing consent. The median expected PFS in the control arm (RVD) is 2.2 years, based on the experience in Total Therapy 3a and 3b studies (high risk genomics defined by 70-gene model). Assuming uniform accrual of 25 patients per year, four years of accrual and an additional 2 years of follow-up yields a study with 82% power and a one-sided significance level alpha of 0.1 to detect a hazard ratio of 1.75 between two treatment arms, or an increase in median PFS from 2 years to 3.5 years in the RVD-Elo arm versus the RVD arm.

Clinical trial information: NCT01668719.

Author(s): Saad Zafar Usmani, Antje Hoering, Rachel Sexton, Sikander Ailawadhi, Jatin J. Shah, Sandi Fredette, Brian G. Durie, Jeffrey A. Zonder, Madhav V. Dhodapkar, S. Vincent Rajkumar, Anuj Kumar Mahindra, Todd M. Zimmerman, Paul G. Richardson, Robert Z. Orlowski; Carolinas Healthcare System, Charlotte, NC; Cancer Research and Biostatistics, Seattle, WA; SWOG Statistical Center, Seattle, WA; University of Southern California Norris Cancer Center, Los Angeles, CA; The University of Texas MD Anderson Cancer Center, Houston, TX; SWOG Operations Office, San Antonio, TX; International Myeloma Foundation and Cedars-Sinai Comprehensive Cancer Center, Los Angeles, CA; Karmanos Cancer Institute, Wayne State University, Detroit, MI; Yale Cancer Center, New Haven, CT; Mayo Clinic, Rochester, MN; Massachusetts General Hospital Cancer Center, Boston, MA; Department of Medicine, University of Chicago, Chicago, IL; Dana-Farber Cancer Institute, Boston, MA

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Dr. Saad Usmani is Chief of Plasma Cell Disorders and Director of Clinical Research in Hematologic Malignancies at the Levine Cancer Institute Hematologic Oncology and Blood Disorders and Carolinas HealthCare System.

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