Session: 653. Myeloma/Amyloidosis: Therapy, excluding Transplantation: Poster II
Hematology Disease Topics & Pathways:
multiple myeloma, Diseases, Elderly, Plasma Cell Disorders, Lymphoid Malignancies, Study Population, Clinically relevant
Methods: Patients with RRMM must have received ≥2 prior lines of therapy, including an IMiD and a proteasome inhibitor, and been refractory to pomalidomide and/or an anti-CD38 monoclonal antibody. Pts received melflufen 40 mg intravenously on day 1 and dex 40 mg per week (20 mg in patients aged ≥75 years) during each 28-day treatment cycle until disease progression or unacceptable toxicity. The primary endpoint was overall response rate (ORR; ≥ partial response [PR]; investigator-assessed per International Myeloma Working Group criteria). Secondary endpoints included progression-free survival (PFS), OS, duration of response (DOR), and safety. An analysis was conducted in the intention-to-treat population for patients aged ≥75 years.
Results: As of the data cutoff date (January 14, 2020), 157 patients were enrolled and treated; 25 (16%) were aged ≥75 years. Baseline characteristics for older patients were generally similar to that of the overall population and were indicative of a heavily pretreated population with a poor prognosis. Among patients aged ≥75 years, the median age was 77 years (range, 75-86); 32% had International Staging System stage 3; and 24% had extramedullary disease. Patients had received a median of 5 prior lines of therapy (range, 2-8), and 76% had triple-class–refractory MM.
Efficacy results were consistent with those of the overall population and were not affected negatively by advanced patient age. ORR was 32% and 29% in patients aged ≥75 years and in the overall population, respectively (Table). In responding patients, median DOR was not reached in patients aged ≥75 years and was 5.5 months in the overall population. In patients aged ≥75 years and the overall population, median PFS was 5.6 months and 4.2 months, respectively, and median OS was 13.5 months and 11.6 months, respectively.
In patients aged ≥75 years and the overall population, respectively, grade 3/4 AEs occurred in 96% and 89% of patients, most commonly neutropenia (44% and 53%), white blood cell count decrease (44% and 26%), thrombocytopenia (40% and 57%), and anemia (40% and 43%); the most common nonhematologic grade 3/4 AEs were pneumonia (20% and 10%), hypertension (12% and 2%), febrile neutropenia (12% and 6%), and hypophosphatemia (12% and 5%). Serious AEs occurred in 40% of patients aged ≥75 years and in 49% of the overall population, most commonly, pneumonia (16% [4 events] and 9% [14 events]); all other serious AEs in patients aged ≥75 years were observed in 1 patient each (4%). There were no treatment-related deaths.
Conclusion: Melflufen, once monthly infusion, plus weekly dex demonstrated clinically meaningful efficacy and a manageable safety profile in older patients with heavily pretreated RRMM. In patients aged ≥75 years, treatment resulted in durable responses, with a safety profile consistent with that in previous reports. Further study is warranted to confirm these results suggesting that melflufen may be an efficacious, convenient, and tolerable therapy for elderly patients with RRMM who have limited treatment options.
Disclosures: Larocca: Amgen: Honoraria; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Honoraria; Takeda: Membership on an entity's Board of Directors or advisory committees. Richardson: Celgene/BMS, Oncopeptides, Takeda, Karyopharm: Research Funding. Oriol: Janssen: Consultancy; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Sanofi: Membership on an entity's Board of Directors or advisory committees. Blade Creixenti: Takeda: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees. Cavo: Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel accomodations, Speakers Bureau; GlaxoSmithKline: Honoraria, Speakers Bureau; Karyopharm: Honoraria; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel accomodations, Speakers Bureau; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Rodríguez-Otero: Janssen, BMS: Other: Travel, accommodations, expenses; BMS, Janssen, Amgen: Honoraria; Janssen, BMS, AbbVie, Sanofi, GSK, Oncopeptides, Kite, Amgen: Consultancy, Honoraria; Celgene-BMS: Consultancy, Honoraria; Mundipharma: Research Funding. Leleu: Janssen: Honoraria. Nadeem: Adaptive: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Janssen: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees. Hassoun: Celgene: Research Funding; Takeda: Research Funding; Novartis: Consultancy. Touzeau: Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Amor: Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene-BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; GSK: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees. Paner: Celgene: Consultancy; Oncopeptides: Consultancy; Kayropharm: Consultancy; Amgen: Consultancy; GSK: Consultancy. Maisel: Takeda: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Karyopharm: Honoraria, Speakers Bureau; Kite: Honoraria, Speakers Bureau; Celgene: Honoraria, Speakers Bureau; Incyte: Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Texas Oncology: Current Employment; Karyopharm: Honoraria, Speakers Bureau; Incyte: Honoraria, Speakers Bureau; Kite: Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau; Texas Oncology: Current Employment; Celgene: Honoraria, Speakers Bureau. Mazumder: Celgene: Honoraria, Speakers Bureau; The Oncology Institute: Current Employment; Amgen: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau. Raptis: INTEGRA: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; UPMC: Current Employment. Puig: JANSSEN: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Research Funding; THE BINDING SITE: Consultancy, Honoraria; AMGEN: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Research Funding; BRISTOL-MYERS SQUIBB: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Research Funding, Speakers Bureau; CELGENE: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Research Funding, Speakers Bureau; TAKEDA: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Research Funding. Thuresson: Statisticon: Current Employment; Oncopeptides: Consultancy, Current equity holder in publicly-traded company. Harmenberg: Oncopeptides AB: Consultancy, Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Ultupharma AB: Current equity holder in private company; Medivir AB: Current equity holder in publicly-traded company. Gustavsson: PiezoMotor AB: Current equity holder in publicly-traded company; Sangus Jazz AB: Current equity holder in private company; Bristol-Myers Squibb: Divested equity in a private or publicly-traded company in the past 24 months; Celgene: Divested equity in a private or publicly-traded company in the past 24 months; XSpray AB: Divested equity in a private or publicly-traded company in the past 24 months; Vinnova: Honoraria; Episurf AB: Current equity holder in publicly-traded company; Nanexa AB: Current equity holder in publicly-traded company, Honoraria, Membership on an entity's Board of Directors or advisory committees; Oncopeptides AB: Current Employment, Current equity holder in publicly-traded company. Mateos: GlaxoSmithKline: Honoraria; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive: Honoraria, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Regeneron: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees.
OffLabel Disclosure: This is a phase 2 investigational study of melflufen in RRMM.
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