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2133 Results of an Early Access Treatment Protocol (EAP) of Daratumumab in United States Patients with Relapsed or Refractory Multiple MyelomaClinically Relevant Abstract

Myeloma: Therapy, excluding Transplantation
Program: Oral and Poster Abstracts
Session: 653. Myeloma: Therapy, excluding Transplantation: Poster I
Saturday, December 3, 2016, 5:30 PM-7:30 PM
Hall GH (San Diego Convention Center)

Ajai Chari, MD1, Tomer M Mark, MD, MSc2, Amrita Krishnan3, Keith Stockerl-Goldstein4, Saad Z Usmani, MD, FACP5, Anil Londhe6*, Delores Etheredge7*, Hollee Parros8*, Sarah Fleming7*, Baolian Liu9*, Scott Freeman6*, Jon Ukropec, PhD6*, Thomas Lin6 and Sagar Lonial, MD, FACP10

1Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY
2Center of Excellence for Lymphoma and Myeloma, Weill Cornell Medical College, New York, NY
3Judy and Bernard Briskin Myeloma Center, City of Hope, Duarte, CA
4Washington University School of Medicine, Siteman Cancer Center, Saint Louis, MO
5Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute/Carolinas HealthCare System, Charlotte, NC
6Janssen Scientific Affairs, LLC, Horsham, PA
7Janssen Research & Development, LLC, Titusville, NJ
8Janssen Research & Development, LLC, Horsham, PA
9Janssen Research & Development, LLC, Spring House, PA
10Winship Cancer Institute, Emory University, Atlanta, GA

Background: Daratumumab (dara) is a human CD38-directed monoclonal antibody indicated for the treatment of patients (pts) with multiple myeloma (MM) who have received ≥3 prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent (IMID) or who are double-refractory to a PI and an IMID. Accelerated approval was granted in the United States (US) in November 2015, based largely on the results of MMY2002, a pivotal phase 2 study in this pt population.

Methods: The objectives of this multicenter, open-label early access treatment protocol (EAP) were to provide early access to dara treatment and collect safety and patient-reported outcome (PRO) data in this pt population. Eligibility criteria were similar to those of pivotal study MMY2002 and included age ≥18 years, documented MM, progression by IMWG criteria following the most recent therapy, ≥3 prior lines of therapy including a PI and an IMID or disease double-refractory to a PI and an IMID, ECOG performance status score 0-2, no known chronic obstructive pulmonary disease or persistent asthma, no ongoing MM therapy, and no prior exposure to anti-CD38 antibody therapy. Pts received dara 16 mg/kg IV weekly for 8 weeks, then every 2 weeks for 16 weeks, and then every 4 weeks until disease progression, unacceptable toxicity, or 60 days after US approval. Pre- and post-infusion medications were administered as in study MMY2002. Serious adverse events (SAEs), grade 3-4 AEs, infusion related reactions (IRRs), and PRO data were collected.

Results: In total, 400 pts were screened and 348 pts were enrolled and dosed at 39 US sites from July to November 2015. Median age was 65 (range 27-94) years; 72% were white, and 17% were African American. Three-fourths of pts were symptomatic with an ECOG score of 1 (58%) or 2 (16%). Pts received a median of 8 (range 1-17) doses, and median treatment exposure was 1.9 (range 0.03-6.0) months. Median durations of infusion were 7.4, 4.4, and 3.5 hours for the first, second, and all subsequent infusions, respectively. Half of pts (52%) transitioned to commercial drug after marketing authorization, whereas 37% discontinued due to progressive disease. Treatment emergent grade >3 AEs were reported in 51% of pts. The most common grade ≥3 AEs were thrombocytopenia (15%) and anemia (14%). SAEs occurred in 35% of pts, including 12% of pts with SAEs which were reported by investigators as drug-related. The most common SAEs were infections, which occurred in 11% of pts. Nine percent of pts discontinued therapy due to AEs, including 3% for drug-related AEs. Thirteen (4%) pts had an AE with a fatal outcome, including 2 (0.6%) pts with drug-related AEs (pyrexia, thrombocytopenia/ subdural hematoma). IRRs occurred in 56% of pts, including 8% with grade >3 IRRs. IRRs occurred in 56%, 2%, and 2% of first, second, and all subsequent infusions, respectively; the most common IRRs were respiratory or thoracic symptoms (cough, dyspnea, throat irritation, nasal congestion), which occurred in 31% of pts. The median change from baseline in all the domains of the EQ-5D-5L and EORTC QLQ-C30 scales after 1 and 2 cycles as well as at pts’ last assessment was 0, with the exception of EQ-5D-5L VAS, which showed a median increase of 1 and 2 units after 1 and 2 cycles, respectively.

Conclusions: EAP results in US pts confirmed the safety profile of dara in MM pts with >3 prior therapies including a PI and IMID or who were refractory to both PI and IMID. SAEs occurred in one-third of pts, but only 12% of pts experienced a drug-related SAE. More than half of pts experienced IRRs, which primarily occurred during the first infusion and were grade 1-2 in severity. Pts maintained their health-related quality of life during a median duration of 2 months of therapy.

Disclosures: Chari: Array Biopharma: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Amgen Inc.: Honoraria, Research Funding; Takeda: Consultancy, Research Funding; Pharmacyclics: Research Funding. Mark: Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Research Funding, Speakers Bureau; Bristol Myers Squibb: Speakers Bureau. Stockerl-Goldstein: Janssen: Speakers Bureau. Usmani: Amgen: Consultancy, Research Funding, Speakers Bureau; BioPharma: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Research Funding; Onyx: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Research Funding; Skyline: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Array: Research Funding; Millennium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Speakers Bureau. Londhe: Janssen Scientific Affairs, LLC: Employment. Etheredge: Janssen Research & Development, LLC: Employment. Parros: Janssen Research & Development, LLC: Employment. Fleming: Janssen Global Services, LLC: Employment. Liu: Janssen Research & Development, LLC: Employment. Freeman: Janssen Scientific Affairs, LLC: Employment. Ukropec: Janssen Scientific Affairs, LLC: Employment. Lin: Janssen Scientific Affairs, LLC: Employment. Lonial: BMS: Consultancy; Novartis: Consultancy; Celgene: Consultancy; Janssen: Consultancy; Onyx: Consultancy; Merck: Consultancy; Onyx: Consultancy; Janssen: Consultancy; BMS: Consultancy; Celgene: Consultancy; Millenium: Consultancy; Novartis: Consultancy.

*signifies non-member of ASH