(C) Specific IgG titers (mg/mL) at baseline, as well as 4 and 8 weeks following type B vaccination in 17 daratumumab-treated RRMM patients. during daratumumab therapy. In addition, daratumumab-treated RRMM patients produced protective IgG antibody titers following vaccination against type B and seasonal influenza, to a similar extent as observed in daratumumab-na?ve RRMM patients. We first examined the levels of expression of CD38 on the surface of normal PC in BM samples from healthy controls, and on MM cells in BM samples obtained from RRMM patients, treated in the GEN501 study, before initiation of daratumumab monotherapy (NCT00574288) (and type B during daratumumab monotherapy (first a part of DARA/ATRA study) (vaccination consisted of the conjugated PCV-13 vaccine (Prevenar, Pfizer) followed by the polysaccharide PPV-23 vaccine (Pneumovax, Merck Sharp & Dohme), both administered intramuscularly with an 8-week interval.7 Specific antibody titers were measured using an enzyme-linked immunoabsorbent assay (ELISA) at baseline, as well as 4 and 8 weeks after each vaccine. Response was defined as an absolute titer 2 mg/mL or a 2-fold increase in six out of nine analyzed pneumococcal subtypes (6B, 8, 9, 14, 15B, 19F, 20, 23F and 33F).8 vaccination consisted of a single intramuscular dose of Act-Hib (Sanofi), and specific antibody titers were assessed using ELISA at baseline, as well as 4 and 8 weeks following vaccination. Response was defined as an absolute titer 1 mg/mL, Ankrd1 or a 4-fold increase in titer (for details see Corynoxeine the and type B vaccinations were observed between daratumumab-treated (68.8% and 66.7%, respectively) and daratumumab-na?ve patients (55.6% and 62.5%, respectively; at baseline, and retained immunity.8 These results are similar to, or better than, those previously reported in less heavily pretreated Corynoxeine MM patients.8C11 Open in a separate window Determine 3. Response to type B, and seasonal influenza vaccination in daratumumab-treated and daratumumab-na?ve patients with relapsed/refractory multiple myeloma. (A) Specific IgG titers (g/mL) against pneumococcal serotypes 6B, 8, 9, 14, 15B, 19F, 20, 23F and 33F, assessed by enzyme-linked immunosorbent assay (ELISA), at baseline and at best response following PCV-13 and PPV-23 vaccination in 16 daratumumab-treated patients with refractory/relapsed multiple myeloma (RRMM). Connected dots represent individual patients. One individual was lost to follow-up and excluded from response evaluation. (B) Specific IgG titers (mg/mL) to the aforementioned pneumococcal serotypes, assessed by ELISA, at baseline and at best response in nine daratumumab-na?ve RRMM patients. Connected dots represent individual Corynoxeine patients. One patient was not evaluable for response due to disease progression requiring a new treatment regimen, which included daratumumab. (C) Specific IgG titers (mg/mL) at baseline, as well Corynoxeine as 4 and 8 weeks following type B vaccination in 17 daratumumab-treated RRMM patients. Bars represent imply titer standard error of imply (SEM). (D) Specific IgG titers (mg/mL) at baseline, as well as 4 and 8 weeks following H.influenzae type B vaccination in ten daratumumab-na?ve RRMM patients. Bars represent imply titer SEM. (E) Strain-specific hemagglutinin inhibition assay geometric mean titers at baseline, as well as 3 and 12 weeks following seasonal influenza vaccination in 13 daratumumab-treated RRMM patients. Bars represent imply SEM. (F) Seroprotection and seroconversion rates to the three influenza strains included in the seasonal influenza vaccination in 13 daratumumab-treated RRMM patients. *In one patient, seroconversion rates could not be assessed because of Corynoxeine missing baseline titers. This individual experienced seroprotective titers against H3N2 and H1N1. #One patient experienced seroprotective titers against all three strains. type B. This individual did not develop protective antibody titers against following vaccination. The infection resolved completely with antibiotic treatment. To the best of our knowledge, none of the other infections was caused by or influenza (for details, see the Online Supplementary Methods). In conclusion, our data show that daratumumab reduces the frequency of normal PC, which is reflected in reduced levels of polyclonal IgA,.