Novel Antibody-Drug Conjugate in Resistant Multiple Myeloma
Posted: Thursday, March 21, 2019
Patients with relapsed or refractory multiple myeloma did not seem to respond to DFRF4539A, an anti-FcRH5 antibody-drug conjugate to the antimitotic agent monomethyl auristatin E, according to a phase I trial published in Blood Cancer Journal. Although A. Keith Stewart, MB, CHB, of Mayo Clinic, Phoenix, and colleagues concluded that the treatment was unsuccessful, FcRH5, a cell-surface marker enriched on diseased plasma cells versus normal tissues or other hematologic malignancies, remains a valid myeloma target.
“Drugs with other mechanisms of action, including T-cell directing, bispecific antibodies, or chimeric antigen receptor–modified T cells, may prove beneficial to multiple myeloma patients in the future, when directed against FcRH5,” the authors concluded.
DFRF4539A was given intravenously to 39 patients. Two dosage regimens were assessed: 0.3 to 2.4 mg/kg every 3 weeks and 0.8 to 1.1 mg/kg weekly.
Overall, the authors observed 37 adverse events (95%), 8 serious adverse events (21%), and 15 grade 3 or higher adverse events (39%). The most common treatment-related adverse event was anemia (n = 10). No deaths were reported, although 2 patients reported grade 3 acute renal failure. The maximum tolerated dose was not reached.
At the tested dosage regimens, the authors observed limited activity. Partial response, minimal response, and stable disease were observed in 2 patients (5%), 1 patient (3%), and 18 patients (46%), respectively. Progressive disease was reported in 16 patients (41%). Although patients did not respond to treatment, the authors confirmed the expression and presence of FcRH5.
Disclosure: The study authors’ disclosure information can be found at www.nature.com.