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4230 Analysis of Outcomes Based on Response in Patients with Relapsed or Relapsed and Refractory Multiple Myeloma Treated with Panobinostat or Placebo in Combination with Bortezomib and Dexamethasone in the Panorama 1 Trial: Updated Analysis Based on Prior Treatment

Myeloma: Therapy, excluding Transplantation
Program: Oral and Poster Abstracts
Session: 653. Myeloma: Therapy, excluding Transplantation: Poster III
Monday, December 7, 2015, 6:00 PM-8:00 PM
Hall A, Level 2 (Orange County Convention Center)

Jesús F San Miguel1, Vânia TM Hungria2, Sung-Soo Yoon3, Meral Beksac, MD4, Meletios A. Dimopoulos5, Ashraf Elghandour, MD6*, Wieslaw W. Jedrzejczak, MD7*, Andreas Guenther, MD8, Thanyaphong Na Nakorn, MD9*, Noppadol Siritanaratkul10, Robert L. Schlossman, MD11, Jian Hou, MD, PhD12*, Philippe Moreau13*, Sagar Lonial, MD14,15, Jae Hoon Lee16*, Hermann Einsele, MD17, Monika Sopala, PhD18*, Bourras-Rezki Bengoudifa, MS18*, Claudia Corrado, MD18*, Florence Binlich19* and Paul G. Richardson, MD11

1Clínica Universidad de Navarra-CIMA, Pamplona, Spain
2Santa Casa de Misericórdia de São Paulo, Sao Paulo, Brazil
3Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea
4Ankara University Faculty of Medicine Department of Hematology, Ankara, Turkey
5National and Kapodistrian University of Athens, Athens, Greece
6Alexandria University, Qesm Bab Sharqi, Egypt
7Hematology, Oncology and Internal Diseases, Medical University of Warsaw, Warsaw, Poland
8University of Kiel, Kiel, Germany
9Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
10Department of Pediatrics and Internal Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
11Dana-Farber Cancer Institute, Boston, MA
12Department of Hematology, The Myeloma & Lymphoma Center, Changzheng Hospital, The Second Military Medical University, Shanghai, China
13Department of Hematology, Nantes University Hospital, Nantes, France
14Winship Cancer Institute, Emory University, Atlanta, GA
15Winship Cancer Institute of Emory University, Department of Hematology and Medical Oncology, Atlanta, GA
16Gachon University Gil Medical Center, Incheon, South Korea
17Department of Internal Medicine II, University Hospital of Wuerzburg, Wuerzburg, Germany
18Novartis Pharma AG, Basel, Switzerland
19Novartis Pharma SAS, Rueil-Malmaison, France

Introduction: Panobinostat (PAN), a potent pan-deacetylase inhibitor, was the first agent of its class to produce a statistically significant and clinically meaningful increase in the median progression-free survival (PFS) of patients (pts) with relapsed or relapsed and refractory multiple myeloma (MM) in a phase 3 trial. In the PANORAMA 1 trial, the addition of PAN to treatment with bortezomib (BTZ) and dexamethasone (Dex; PAN-BTZ-Dex) led to a significant increase in high-quality responses (near-complete response/complete response [nCR/CR]; 27.6%) vs treatment with placebo (Pbo), BTZ, and Dex (15.7%; P = .00006). Pts in the PAN-BTZ-Dex arm also had a significantly prolonged median PFS of 12.0 months vs 8.1 months in pts treated with Pbo-BTZ-Dex (hazard ratio [HR], 0.63; P < .0001). Further, subgroup analysis showed that the PFS benefit was maintained in pts with previous exposure to BTZ and immunomodulatory drugs (IMiDs; 10.6 vs 5.8 months; HR, 0.52). These results supported the recent US FDA approval of PAN in combination with BTZ and Dex for the treatment of pts with relapsed or relapsed and refractory MM who have received ≥ 2 prior regimens including BTZ and an IMiD. Here, we present a detailed analysis of the effect of response on clinical outcomes in a subpopulation of PANORAMA 1 pts with prior exposure to BTZ and IMiDs.

Methods: Response outcomes were analyzed for the subgroup of PANORAMA 1 pts with prior exposure to BTZ and IMiDs based on modified European Society for Blood and Marrow Transplantation criteria, including nCR/CR and partial response (PR). A landmark analysis at 12, 18, and 24 weeks was performed using a Cox regression model to assess the median PFS in pts who achieved nCR/CR and PR.

Results: Among pts with prior exposure to BTZ and IMiDs, the nCR/CR rate was higher in the PAN-BTZ-Dex arm (22.3% [95% CI, 14.4-32.1]) vs the Pbo-BTZ-Dex arm (9.9% [95% CI, 4.2-16.6]). In the PAN-BTZ-Dex arm, the landmark analysis at 12 weeks demonstrated a median PFS of 13.7 months in pts achieving nCR/CR vs 8.1 months in pts achieving PR (HR, 0.34 [95% CI, 0.12-0.96]). Similarly, pts achieving nCR/CR in the Pbo-BTZ-Dex arm had a median PFS of 12.2 vs 7.8 months for pts achieving a PR (HR, 0.74 [95% CI, 0.27-2.01]). Landmark analysis at 18 weeks demonstrated a median PFS of 15.8 months for pts with nCR/CR vs 10.3 months for pts with a PR in the PAN arm (HR, 0.30 [95% CI, 0.12-0.75]) and 14.1 vs 9.0 months (HR, 0.76 [95% CI, 0.29-1.98]) in the Pbo arm for pts with nCR/CR and PR, respectively. The 24 week landmark assessment revealed a median PFS in the PAN arm of 15.8 months for pts with nCR/CR vs 13.7 months for pts with PR (HR, 0.32 [95% CI, 0.14-0.74]) and, in the Pbo arm, a median PFS of 12.2 months for pts with nCR/CR vs 11.2 months in pts with PR (HR, 0.93 [95% CI, 0.36-2.43]).

Conclusions: Treatment with PAN-BTZ-Dex is associated with a > 2-fold increase in the rate of nCR/CR in pts with relapsed or relapsed and refractory MM compared with control arm. Among study pts who had received prior treatment with BTZ + IMiDs, those who achieved nCR/CR after treatment with PAN-BTZ-Dex demonstrated a prolonged PFS compared to pts who achieved PR. These data highlight the importance of achieving deep responses with PAN-BTZ-Dex in this subpopulation, suggesting that the achievement of such responses may be linked to improved clinical outcomes.

Disclosures: San Miguel: Millennium: Membership on an entity’s Board of Directors or advisory committees ; Celgene: Membership on an entity’s Board of Directors or advisory committees ; Novartis: Membership on an entity’s Board of Directors or advisory committees ; Onyx: Membership on an entity’s Board of Directors or advisory committees ; Janssen: Membership on an entity’s Board of Directors or advisory committees ; BMS: Membership on an entity’s Board of Directors or advisory committees ; MSD: Membership on an entity’s Board of Directors or advisory committees . Beksac: Janssen-Cilag: Consultancy , Speakers Bureau ; Novartis: Consultancy , Honoraria , Membership on an entity’s Board of Directors or advisory committees ; Takeda: Consultancy , Honoraria , Membership on an entity’s Board of Directors or advisory committees ; Bristol-Myers Squibb: Consultancy , Membership on an entity’s Board of Directors or advisory committees , Speakers Bureau ; Amgen: Honoraria , Membership on an entity’s Board of Directors or advisory committees , Speakers Bureau ; Celgene: Consultancy , Speakers Bureau . Dimopoulos: Onyx: Honoraria ; Novartis: Honoraria ; Amgen: Honoraria ; Genesis: Honoraria ; Janssen-Cilag: Honoraria ; Celgene: Honoraria ; Janssen: Honoraria . Jedrzejczak: Pfizer: Membership on an entity’s Board of Directors or advisory committees ; Roche: Membership on an entity’s Board of Directors or advisory committees ; Novartis: Membership on an entity’s Board of Directors or advisory committees ; Celgene: Membership on an entity’s Board of Directors or advisory committees ; Onconova: Membership on an entity’s Board of Directors or advisory committees ; Janssen: Membership on an entity’s Board of Directors or advisory committees . Siritanaratkul: Pfizer: Research Funding ; Roche: Research Funding ; Novartis: Research Funding ; Janssen-Cilag: Research Funding . Schlossman: Millennium: Consultancy . Hou: Novartis: Membership on an entity’s Board of Directors or advisory committees . Moreau: Celgene: Honoraria , Membership on an entity’s Board of Directors or advisory committees ; Millennium: Honoraria , Membership on an entity’s Board of Directors or advisory committees ; Novartis: Honoraria , Membership on an entity’s Board of Directors or advisory committees ; Bristol-Myers Squibb: Honoraria , Membership on an entity’s Board of Directors or advisory committees ; Janssen-Cilag: Honoraria , Membership on an entity’s Board of Directors or advisory committees . Lonial: Onyx: Consultancy , Research Funding ; Novartis: Consultancy , Research Funding ; Celgene: Consultancy , Research Funding ; Janssen: Consultancy , Research Funding ; Millennium: Consultancy , Research Funding ; Bristol-Myers Squibb: Consultancy , Research Funding . Einsele: Janssen: Consultancy , Honoraria , Research Funding , Speakers Bureau ; Celgene: Consultancy , Honoraria , Research Funding , Speakers Bureau ; Novartis: Consultancy , Honoraria , Research Funding , Speakers Bureau ; Amgen/Onyx: Consultancy , Honoraria , Research Funding , Speakers Bureau . Sopala: Novartis Pharma: Employment , Equity Ownership . Bengoudifa: Novartis: Employment . Corrado: Novartis: Employment , Equity Ownership . Binlich: Novartis: Employment . Richardson: Celgene Corporation: Membership on an entity’s Board of Directors or advisory committees ; Millennium Takeda: Membership on an entity’s Board of Directors or advisory committees ; Gentium S.p.A.: Membership on an entity’s Board of Directors or advisory committees , Research Funding ; Jazz Pharmaceuticals: Membership on an entity’s Board of Directors or advisory committees , Research Funding ; Novartis: Membership on an entity’s Board of Directors or advisory committees .

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