Safety Profile of Oral Ixazomib: Experience from 761 Patients (Pts) Across 14 Phase 1 or Phase 1/2 Clinical Studies

Abstract

e78 BP-055 Subgroup Analysis by Prior Treatment of the Efficacy and Safety of Panobinostat Plus Bortezomib and Dexamethasone in Patients With Relapsed or Relapsed and Refractory Multiple Myeloma in the PANORAMA 1 Study P.G. Richardson, V.T.M. Hungria, S.-S. Yoon, M. Beksac, M.A. Dimopoulos, A. Elghandour, W.W. Jedrzejczak, A. Guenther, T.N. Nakorn, N. Siritanaratkul, R.L. Schlossman, J. Hou, P. Moreau, S. Lonial, J.H. Lee, H. Einsele, M. Sopala, B.R. Bengoudifa, C. Corrado, J.F. San-Miguel Dana-Farber Cancer Institute, Boston, MA, USA; Irmandade da Santa Casa de Misericordia de Sao Paulo, Sao Paulo, Brazil; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; Ankara University School of Medicine, Ankara, Turkey; Department of Clinical Therapeutics, University of Athens School of Medicine, Athens, Greece; Alexandria University, Alexandria, Egypt; Medical University of Warsaw, Warsaw, Poland; Division of Stem Cell Transplantation and Immunotherapy, 2 Department of Medicine, University Hospital SchleswigHolstein and University of Kiel, Kiel, Germany; King Chulalongkorn Memorial Hospital and Chulalongkorn University, Bangkok, Thailand; Siriraj Hospital, Bangkok, Thailand; Chang Zheng Hospital, Shanghai, China; University Hospital of Nantes, Nantes, France; Winship Cancer Institute, Atlanta, GA, USA; Department of Internal Medicine, Gachon University Gil Hospital, Incheon, Republic of Korea; Medizinische Klinik und Poliklinik II, University of Wurzburg, Wurzburg, Germany; Novartis Pharma AG, Basel, Switzerland; Clinica Universidad de Navarra, Pamplona, Spain Introduction: Panobinostat (PAN), a potent pan-deacetylase inhibitor, affects processes integral to growth and survival of multiple myeloma (MM) cells through alteration of protein metabolism and epigenetic mechanisms. In the PANORAMA 1 phase 3 trial, combination of PAN with bortezomib (BTZ) and dexamethasone (Dex; PAN-BTZ-Dex) led to a clinically significant increase in progression-free survival (PFS) of z4 mo vs placebo plus BTZ and Dex (Pbo-BTZ-Dex). This analysis examined efficacy and safety of PAN-BTZ-Dex based on prior treatment. Therapeutic options for patients (pts) who have received immunomodulatory agents (IMIDs) and protease inhibitors are limited, and with each relapse these options become progressively restricted by drug resistance or intolerance. Methods: The study design was described previously (San-Miguel JF, Lancet Oncol. 2014). A subanalysis assessed efficacy and safety of PAN-BTZ-Dex in pts based on prior treatment characteristics, including receipt of prior IMiDs, BTZ + IMiDs, and BTZ + IMiDs and 2 prior lines of therapy. Here, we focus on efficacy and safety of PAN-BTZ-Dex in pts with relapsed or relapsed and refractory MM who received 2 prior regimens, including BTZ and an IMiD (n1⁄4147). Results: Pts in the PAN-BTZ-Dex arm (n1⁄473) had improved efficacy compared with those receiving Pbo-BTZ-Dex (n1⁄474). Of note, in the studied subgroup, pts in the PAN arm had Clinical Lymphoma, Myeloma & Leukemia September 2015 a longer median PFS (12.5 mo) than those in the Pbo arm (4.7 mo, HR: 0.47 [95% CI, 0.31-0.72]; Figure). Pts in the PAN arm vs Pbo arm also showed improvements in overall response rate (ORR; 58.9% [95% CI, 46.8%-70.3%] vs 39.2% [28.0%-51.2%]) and complete response/near-complete response (CR/nCR) rate (21.9% [95% CI, 13.1%-33.1%] vs 8.1% [3.0%-16.8%]). Common grade 3/4 adverse events and laboratory abnormalities in the PAN arm vs Pbo arm included thrombocytopenia (68.1% vs 44.4%), neutropenia (40.3% vs 16.4%), diarrhea (33.3% vs 15.1%), and asthenia/fatigue (26.4% vs 13.7%). Importantly, incidence of ontreatment deaths was nearly identical in both arms (n1⁄45 [6.9%] vs n1⁄45 [6.8%]). Conclusion: This analysis identified a subpopulation of pts in whom PAN-BTZ-Dex more than doubled the PFS vs PboBTZ-Dex, with marked improvements in CR/nCR rate and ORR. The safety profile was similar to the overall population. Together, these findings support the approval of PAN-BTZ-Dex by the US FDA in pts with relapsed or relapsed and refractory MM with 2 prior regimens, including BTZ and an IMiD. BP-056 Safety Profile of Oral Ixazomib: Experience from 761 Patients (Pts) Across 14 Phase 1 or Phase 1/2 Clinical Studies S. Lonial, K. Colson, R.D. Harvey, S. Kumar, A.-M. Hui, G. Liu, D. Berg, P. Richardson Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, USA; Dana-Farber Cancer Institute, Boston, MA, USA; Division of Hematology, Mayo Clinic, Rochester, MN, USA; Millennium Pharmaceuticals, Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company