Patients with multiple myeloma (MM) are at increased risk for severe clinical symptoms and mortality due to SARS-CoV-2 infection. To protect against these complications, the International Myeloma Society recommends vaccinating all patients with monoclonal gammopathy of undetermined significance (MGUS), monoclonal gammopathies of clinical significance, smoldering MM (SMM), and MM. 1 Protective immunity against SARS-CoV2 in those patients is partially relevant given their increased risk for infections, which may cause significant morbidity and represent the second most frequent cause of mortality. 2 The extent of the immune impairment in MM largely depends on the disease-inherent immune suppression exerted by the malignant clone that can affect all immune effector mechanism including B cells, T cells, NK cell, and dendritic cells, and the complement system. 3, 4 The myeloma-induced immune deficiency can resolve completely during periods of deep response, such as minimal residual disease negativity, but deep responses are achieved in a proportion of patients only, and several of those eventually relapse and become immune suppressed again and/or suffer from other causes of reduced immune competence. Many patients present at older age with comorbidities and immunosenescence5 with an impaired defense against infections and compromised development of long-term immune memory, which is aimed at by vaccination. Myeloma therapy including proteasome inhibitors, dexamethasone, high dose melphalan, monoclonal antibodies, antibody-drug conjugates, BiTEs and cellular therapies, such as CAR-T cells, result in specific and cumulative immune suppression, and after extensive therapy in T cell exhaustion. 6 Hence, myeloma and myeloma treatmentinduced immunosuppression and other above mentioned factors frequently impose critical hurdles for an effective vaccination response in many patients and emerging data seem to underpin these concerns. 7

A recent study in 48 elderly patients with MM (median age 83 years) reported a significantly lower proportion of MM patients with a neutralizing antibody response on day 22 after the first dose of the BNT162b2 vaccine compared to controls of the same age category (20.6% versus 32.5%, respectively). Virus neutralizing antibody titers of≥ 50% deemed to be clinically relevant, were noted in four (8.3%) of 48 patients and in 21 of 104 (20.2%) controls only; all these four patients were in remission without any therapy. 8 Only one of the nine patients with SMM had neutralizing antibody titers. This poor response did not improve substantially with the second dose. Part of the observed low response rate could be due to the high age of the study participants as specific antibody production in response to vaccination declines with older age. 9, 10 Similar results were noted in 93 patients (median age 67 years) after one dose of the BNT162b2 or ChAdOx1-S vaccine. 11 After a median time from first dose to antibody testing of 33days, SARS-CoV-2 IgG antibodies were noted in 55.9% of patients, with no difference between both vaccines.