HORIZON (OP-106): Melflufen Plus Dexamethasone (dex) in Patients (pts) with Relapsed/Refractory Multiple Myeloma (RRMM)-Analysis of Adverse Events Related to Hospitalizations

• Published in: Blood 2020-11, Vol.136 (Supplement 1), p.20-22
• Main Authors: Nadeem, Omar, Richardson, Paul G., Mateos, María-Victoria, Oriol, Albert, Larocca, Alessandra, Blade Creixenti, Joan, Rodríguez-Otero, Paula, Leleu, Xavier, Norkin, Maxim, Hiemenz, John W., Hassoun, Hani, Touzeau, Cyrille, Amor, Adrián Alegre, Paner, Agne, Maisel, Christopher, Mazumder, Amitabha, Raptis, Anastasios, Puig, Noemí, Sandberg, Anna, Pelaez, Ivonne, Jaques, Christian, Orre, Marie, Cavo, Michele
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2020-136000

▪ Background: Pts with RRMM are a very sick population due to disease symptoms, comorbidities, side effects from treatments, and age-related fragility (Chim et al. Leukemia. 2018;32:252). Pts often experience adverse events (AEs) that affect their quality of life and reduce treatment compliance; hematologic AEs are frequent. Inpatient services for the management of AEs are often necessary and a major cost driver, with costs rising per AE episode (highest for hematologic AEs; Felber et al. ASH 2019. Abs. 4725). Additionally, a real-world study suggested that >50% of pts with hematologic AEs require readmittance to the hospital after initial treatment (Yeaw et al. ISPOR 2020. Abs. PCN78). Published data to date come from real-world evidence, with limited reports from clinical trials. Melphalan flufenamide (melflufen) is a first-in-class peptide-drug conjugate (PDC) that targets aminopeptidases and rapidly releases alkylating agents into tumor cells. In the pivotal, phase 2, HORIZON study (OP-106; NCT02963493), melflufen plus dex showed clinically meaningful efficacy and a safety profile consisting primarily of clinically manageable hematologic AEs in pts with heavily pretreated RRMM (Richardson et al. EHA 2020. Abs EP945). This analysis aids to further elucidate the healthcare resource utilization of pts with RRMM treated with melfulfen in a clinical trial by evaluating the impact of AEs on hospitalizations in HORIZON. Methods: Pts with RRMM who had received ≥2 lines of prior therapy, including an IMiD and a proteasome inhibitor and were refractory to pomalidomide and/or an anti-CD38 monoclonal antibody were treated with melflufen and dex as described (Richardson et al. EHA 2020. Abs EP945). Data for specific AEs potentially related to the study drugs (melflufen and/or dex; TRAEs) requiring hospitalizations >24 h were compared with all potential TRAEs and within each preferred term with >1 event reported regardless of hospitalization. AEs were classified as TRAE if reported as related or possibly related to either study drug by the treating physician. Results: At the data cutoff date (14 Jan 2020), 157 pts were enrolled and had received ≥1 dose of study treatment; 35 (22%) had been hospitalized due to a TRAE. Pts hospitalized due to TRAEs had a median age of 63 y (range, 43-84); 31% had International Staging System stage 3 disease; 49% had high-risk cytogenetics; and 77% had triple-class-refractory MM. In the overall population (N=157), the most frequent gra