Spotlight on Melphalan Flufenamide: An Up-and-Coming Therapy for the Treatment of Myeloma

Figures & data

Figure 1 Chemical structure and metabolism of melflufen (melphalan flufenamide) hydrochloride, a dipeptide prodrug of melphalan. Melflufen is metabolized into melphalan and p-Fluorophenylalanine by aminopeptidases (AP) inside myeloma cells. Melflufen utilizes not only intracellular aminopeptidases (AP) but also esterases (ES) to release a melphalan cytotoxic payload in neoplastic myeloma cells.

Table 1 The Main Published Trials Involving RRMM Patients Treated with Melflufen

Trial	Schedule	No of Patients	Median Prior Therapies	Median Follow-Up (Months)	ORR (%)	Median PFS (Months)	Safety Profile
O-12-M1 (Phase I/II) (61, 62)	Melflufen + dexamethasone	45 (Phase II; evaluable for response)	4 (2–14)	27.9	31	5.7	Grade 3/4 TRAEs: thrombocytopenia (58%), neutropenia (58%), anemia (42%); serious TRAEs: 27% (pneumonia 9%)
HORIZON (Phase II) (63)	Melflufen + dexamethasone	157	5 (2–12)	14	29	4.2	Grade 3/4 TRAEs: neutropenia (79%), thrombocytopenia (76%), anemia (43%); serious TRAEs: 49% (pneumonia 9%)
ANCHOR (Phase I/II) (64)	Melflufen + dexamethasone + daratumumab	33	2 (1–4)	11.9	70	11.5	No DLTs grade 3/4 TRAEs: neutropenia (58%), thrombocytopenia (55%), anemia (24%); serious TRAEs: 36% (influenza 9%)
	Melflufen + dexamethasone + bortezomib	10	2.5 (1–4)	NR	60	NR	No DLTs grade 3/4 TRAEs: thrombocytopenia (80%), neutropenia (60%), anemia (40%); serious TRAEs: 60% (pneumonia 20%)

Abbreviations: No, number; ORR, overall response rate; PFS, progression-free survival; NR, not reported; DLT, dose-limiting toxicity; TRAE, treatment-related adverse event.