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Melflufen and Dexamethasone in Heavily Pretreated Relapsed and Refractory Multiple Myeloma
- Source :
- Journal of Clinical Oncology, Journal of Clinical Oncology, 2021, 39 (7), pp.757-767. ⟨10.1200/JCO.20⟩, Journal of Clinical Oncology, American Society of Clinical Oncology, 2021, 39 (7), pp.757-767. ⟨10.1200/JCO.20⟩, Dipòsit Digital de Documents de la UAB, Universitat Autònoma de Barcelona, r-IGTP. Repositorio Institucional de Producción Científica del Instituto de Investigación Germans Trias i Pujol, instname
- Publication Year :
- 2021
- Publisher :
- American Society of Clinical Oncology (ASCO), 2021.
-
Abstract
- PURPOSE Melphalan flufenamide (melflufen) is a first-in-class peptide-drug conjugate that targets aminopeptidases and rapidly and selectively releases alkylating agents into tumor cells. The phase II HORIZON trial evaluated the efficacy of melflufen plus dexamethasone in relapsed and refractory multiple myeloma (RRMM), a population with an important unmet medical need. PATIENTS AND METHODS Patients with RRMM refractory to pomalidomide and/or an anti-CD38 monoclonal antibody received melflufen 40 mg intravenously on day 1 of each 28-day cycle plus once weekly oral dexamethasone at a dose of 40 mg (20 mg in patients older than 75 years). The primary end point was overall response rate (partial response or better) assessed by the investigator and confirmed by independent review. Secondary end points included duration of response, progression-free survival, overall survival, and safety. The primary analysis is complete with long-term follow-up ongoing. RESULTS Of 157 patients (median age 65 years; median five prior lines of therapy) enrolled and treated, 119 patients (76%) had triple-class–refractory disease, 55 (35%) had extramedullary disease, and 92 (59%) were refractory to previous alkylator therapy. The overall response rate was 29% in the all-treated population, with 26% in the triple-class–refractory population. In the all-treated population, median duration of response was 5.5 months, median progression-free survival was 4.2 months, and median overall survival was 11.6 months at a median follow-up of 14 months. Grade ≥ 3 treatment-emergent adverse events occurred in 96% of patients, most commonly neutropenia (79%), thrombocytopenia (76%), and anemia (43%). Pneumonia (10%) was the most common grade 3/4 nonhematologic event. Thrombocytopenia and bleeding (both grade 3/4 but fully reversible) occurred concomitantly in four patients. GI events, reported in 97 patients (62%), were predominantly grade 1/2 (93%); none were grade 4. CONCLUSION Melflufen plus dexamethasone showed clinically meaningful efficacy and a manageable safety profile in patients with heavily pretreated RRMM, including those with triple-class–refractory and extramedullary disease.
- Subjects :
- Adult
Male
Cancer Research
Time Factors
Time Factor
Phenylalanine
[SDV.CAN]Life Sciences [q-bio]/Cancer
Tumor cells
Drug resistance
Dexamethasone
03 medical and health sciences
0302 clinical medicine
[SDV.CAN] Life Sciences [q-bio]/Cancer
Recurrence
Antineoplastic Combined Chemotherapy Protocols
medicine
Humans
Neoplasm
Progression-free survival
Melphalan
Aged
030304 developmental biology
Aged, 80 and over
0303 health sciences
Antineoplastic Combined Chemotherapy Protocol
business.industry
Refractory Multiple Myeloma
Middle Aged
medicine.disease
Progression-Free Survival
United States
3. Good health
Europe
Clinical trial
Oncology
Drug Resistance, Neoplasm
030220 oncology & carcinogenesis
Disease Progression
Cancer research
Female
Multiple Myeloma
business
Human
Conjugate
medicine.drug
Subjects
Details
- ISSN :
- 15277755 and 0732183X
- Volume :
- 39
- Database :
- OpenAIRE
- Journal :
- Journal of Clinical Oncology
- Accession number :
- edsair.doi.dedup.....79bb7c110aefa09f245d7dfe112c3ba4