PURPOSE Vaccine-induced neutralizing antibodies (nAbs) play a critical role in protection from SARS CoV-2. Patients with B-cell malignancies including myeloma are at increased risk of COVID-19–related mortality and exhibit variable serologic response to the vaccine. The capacity of vaccine-induced antibodies in these patients to neutralize SARS CoV-2 or its variants is not known. METHODS Sera from 238 patients with multiple myeloma (MM) undergoing SARS CoV-2 vaccination were analyzed. Antibodies against the SARS CoV-2 spike receptor-binding domain (RBD) and viral nucleocapsid were measured to detect serologic response to vaccine and environmental exposure to the virus. The capacity of antibodies to neutralize virus was quantified using pseudovirus neutralization assay and live virus neutralization against the initial SARS CoV-2 strain and the B1.617.2 (Delta) variant. RESULTS Vaccine-induced nAbs are detectable at much lower rates (54%) than estimated in previous seroconversion studies