r?=?0.69 p??0,0001 Spearman test.(40K, docx) Acknowledgements We warmly thank Sylvie Miconnet, Asmaa Mamoune, Bineta Ly, Juliette Pascaud, Isabelle Bonnet, Elodie Rivire, Marie-Armelle Roudault for their high implication in the vaccination process of the patients Authors’ information Samuel Bitoun and Julien Henry have contributed equally to this work. Abbreviations HCHealthy controlsHSCTHematopoietic stem-cell transplantationIMWGInternational Myeloma Working GroupMMMultiple myeloma Authors’ contributions SB, JH, RS and XM designed research, SB, JH, ND, CVF, LM, CJ, DD, MB, AMR, RLG, RS and XM performed research, SB, JH, RS and XM analyzed data, SB, JH, ND, CVF, LM, DD, CJ, AMR, RLG, RS and XM wrote the paper. a gamechanger. Melagatran We sought to examine response to mRNA vaccine between healthy controls (value(%)0.09?Female ((%)0.65?Had HSCT ((%)0.03?On therapy ((%)?Myeloma in complete response or in very good partial response or partial response ((%)?Daratumumab-based therapy (Hematopoietic stem-cell Melagatran transplantation, International Myeloma Working Group Open in a separate window Fig. 1 a Anti-spike IgG levels compared at day 56 after first vaccine injection between multiple myeloma patients and healthy controls. em p /em ?=?0.0013 using MannCWhitney test. b Neutralizing activity of anti-SARS-CoV-2 antibodies compared at day 56 after first vaccine injection between multiple myeloma patients and Healthy controls. em p /em Rabbit polyclonal to Kinesin1 ?=?0.0002 using MannCWhitney test The main predictive factor of absence of response was MM disease status. Effectively, the only three MM patients with no detectable anti-spike IgG had a progressive or stable MM on therapy (none on daratumumab, Table ?Table1).1). Progressive or stable disease was associated with a worse response to vaccine taking both detectable (3/3 vs. 0/24; em p /em ?=?0.0003 Fischers exact test) or ?50?IU/ml anti-spike IgG thresholds (3/7 vs. 20/20; em p /em ?=?0.01; Fischer test). Residual gammaglobulin level was significantly higher in responders (?50?IU/mL) compared to non-responders (6.1??3.9 vs. 2.3??0.8 mean??SD em p /em ?=?0.0009 MannCWhitney test). Conversely, we found that daratumumab was not associated with worse immunogenicity, since 6/9 (66.7%) patients receiving daratumumab had anti-spike titers ?50?UI/ml versus 14/18 (78%) not receiving daratumumab ( em p /em ?=?0.65). Using a different assay to detect neutralizing anti-SARS-CoV-2 antibodies, we found a higher response rate in the MM group compared to Terpos Melagatran et al. [2], but they assessed Melagatran neutralization after only one injection. Compared to Pimpinelli et al. [1] who assessed immunogenicity after the second injection [1], we had similar response rates (74.1% vs. 78.6% respectively), even though we assessed response a little later (4 vs. 2?weeks after the second dose). However, contrarily to 2 other publications [1, 3] we did not confirm the unfavorable impact of daratumumab on vaccine immunogenicity even though there was a numerical decrease of responders with neutralizing antibodies in those patients (66.7% vs. 78%). This might be due to lack of power in our study. It might also be due to the fact that most of our patients treated with daratumumab were in complete response and we have shown, as others, that active disease was a risk factor of low immunogenicity [3]. Thus, we also identified MM disease status (progressive or stable disease on treatment) regardless of treatment and low residual gammaglobulin level, as the main potential factors of non-response which is in line with was found by Terpos et al. [2] and Van Oekelen et al. [3]. The impact of MM status was not assessed by Pimpinelli et al. Overall, these results support a diminished response to 2 doses of anti?SARS?CoV?2 BNT162b2 vaccine in MM patients compared to HC. Similarly to the previous studies of the literature [1C3], a high proportion of MM patients still achieve a detectable humoral response: 89% in MM versus 97% in HC and neutralizing antibodies: 75% in MM vs 96% in HC. This is to be compared to no response at all in patients treated with anti-CD20-based regimen in chronic lymphocytic leukemia which received this drug in the previous year [4]. Even if most of MM patients achieved humoral immunization, diminished titers of anti-Spike and neutralizing antibodies are of a concern in the era of the delta variant. We identified uncontrolled MM on treatment as the main potential risk factor of non-response to COVID-19 vaccine. This requires confirmation in lager studies. In these patients without response, it is crucial to vaccinate their family members and primary caregivers. The Melagatran use of a third dose should be evaluated in MM patients. Supplementary Information Additional file 1..
