POSTER 39
HORIZON (OP-106): MELFLUFEN PLUS DEXAMETHASONE IN PATIENTS WITH
RELAPSED/REFRACTORY MULTIPLE MYELOMA (RRMM) EXPOSED AND REFRACTORY TO
PRIOR ALKYLATOR THERAPY—SUBGROUP ANALYSIS
Paula Rodríguez-Otero1, María-Victoria Mateos2, Albert Oriol3, Alessandra Larocca4, Joan Bladé5,
Michele Cavo6, Xavier Leleu7, Maxim Norkin8, Omar Nadeem9, John W. Hiemenz10, Hani Hassoun11,
Cyrille Touzeau12, Adrián Alegre13, Agne Paner14, Christopher Maisel15, Amitabha Mazumder16,
Anastasios Raptis17, Noemí Puig18, Marcus Thuresson19, Johan Harmenberg19, Olof Harlin19 and Paul G.
Richardson9
(1)Clinica Universidad de Navarra, Pamplona, Spain
(2)Hospital Clinico Universitario de Salamanca/IBSAL/CIC, Salamanca, Spain
(3)Institut Català d’Oncologia, Institut Josep Carreras, Hospital Germans Trias i Pujol, Barcelona, Spain
(4)Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospedaliero – Universitaria
Città della Salute e della Scienza, Torino, Italy
(5)Hematology Department, IDIBAPS, Hospital Clinic, Barcelona, Spain
(6)Seràgnoli Institute of Hematology, Bologna University School of Medicine, Bologna, Italy
(7)CHU de Poitiers, Poitiers, France
(8)Baptist MD Anderson Cancer Center, Jacksonville
(9)Dana-Farber Cancer Institute, Harvard Medical School, Boston
(10)Division of Hematology-Oncology, Department of Medicine, University of Florida, Gainesville
(11)Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York
(12)Service d'hématologie Clinique, Centre Hospitalier Universitaire, Place Alexis Ricordeau, Nante,
France
(13)Hospital Universitario La Princesa and Hospital Universitario Quironsalud, Madrid, Spain
(14)Rush University Medical Center, Chicago
(15)Baylor Scott & White Charles A. Sammons Cancer Center, Dallas
(16)The Oncology Institute of Hope and Innovation, Glendale
(17)Division of Hematology-Oncology, Department of Medicine, University of Pittsburgh School of
Medicine, Pittsburgh
(18)Hospital Clínico Universitario de Salamanca/IBSAL/CIC, Salamanca
(19)Oncopeptides AB, Stockholm, Sweden
Background: Standard-of-care regimens in MM combine multiple drug classes. Because most patients
relapse, therapies with novel mechanisms of action are needed. Melphalan flufenamide (melflufen) is
a first-in-class peptide-drug conjugate (PDC) that leverages aminopeptidases and rapidly releases
alkylating agents into tumor cells. In the phase 2 HORIZON study (NCT02963493), melflufen plus
dexamethasone showed meaningful efficacy and a clinically manageable safety profile in advanced
RRMM (Richardson, et al. J Clin Oncol. 2020 Dec 9 Epub). This analysis examined subsets of patients
exposed/refractory to prior alkylator therapy.
Methods: Patients with RRMM had received ≥2 prior lines of therapy (LoTs; including an IMiD and a
proteasome inhibitor) and were refractory to pomalidomide and/or an anti-CD38 monoclonal
antibody. Patients received melflufen 40 mg intravenously on day 1 of each 28-day cycle plus
dexamethasone 40 mg/week until progressive disease or unacceptable toxicity. Primary endpoint:
overall response rate (ORR; ≥ partial response; assessed by the investigator per International Myeloma
Working Group response criteria). Secondary endpoints: duration of response (DOR), progression-free
survival (PFS), overall survival (OS), and safety.
Results: Of 92 patients refractory to prior alkylator therapy (median time since last exposure, 1.3 years;
data cutoff: 14 January 2020), 37 (40%) were exposed/refractory to 1 LoT; 30 (33%) were exposed to