question: Background The worldwide COVID-19 pandemic represents an unprecedented crisis that affects the entire medical community, and appears to be a devastating infection in patients with hematological disorders, including myeloma (MM). Vaccination is therefore crucial in this population. Seroconversion after COVID-19 has been shown to be lower in MM patients compared to the general population. The same is expected after vaccination, as different reports have already revealed a lower antibody response after anti-SARS-CoV-2 vaccination in this group. We investigated the role of anti-SARS-CoV-2 vaccination in our MM patients. Method We collected data on the occurrence and outcome of COVID-19, and impact of anti-SARS-CoV-2 vaccination in patients with MM or related disorders, excluding MGUS. Diagnosis of COVID-19 relied on a positive RT-PCR nasopharyngeal swab, while immunization was assessed after two shots of either a mRNA (Pfizer®/Moderna®) or a viral vector (Astra Zeneca®) vaccine, using the Elecsys immunoassay (Roche®) that measures anti-SARS-CoV-2 antibodies including IgG. Results From March 2020 to date, 219 patients with plasma cell dyscrasias were seen on a regular basis at our outpatient facility. Only 15 of them were diagnosed with COVID-19 (median age 71, range 55-85), with an adverse outcome occurring in 3 patients with an advanced disease. We then collected the serological status at day 30, of the first 129 patients that completed vaccination. 97 were affected by MM, 19 by SMM, 3 by MGRS, 10 by AL amyloidosis. 118 developed regular antibodies confirmed by the presence of the receptor binding domain of the spike protein (RBD) antibodies, while 7 presented nucleocapsid protein (N) antibodies, suggesting a previous contact with the virus in the absence of any clinical manifestation. 11 patients failed to develop any immunization, all had received immunosuppressive therapies (renal transplantation in 1, long-term corticosteroid in 1, cyclophosphamide in 7, anti-CD20 monoclonal antibodies in 2) or multiple previous lines of therapies. We could not identify any link with immunoparesis or CD4/CD8 levels, additional tests are pending. With a 3 month median follow up, only 1 patient experienced a mild form of COVID-19 after vaccination despite high levels of neutralizing antibodies. Conclusion So far, SARS-CoV-2 vaccination provides an adequate coverage in our MM population since only one case of COVID-19 occurred after vaccination. Extended follow-up will however be needed to confirm this, particularly with the appearance of new variants, and to know how long this protection will last over time. Whether non responding patients will eventually develop T-cell protection against COVID-19 remains also to be answered, as well as the positivity cutoff that measures neutralizing antibodies, optimal timing of vaccination, particularly in the context of immunodeficiency and diverse anti-MM therapies, and the role of a third shot in specific situations.