P27: humoral response rate post mrna covid19 vaccination (bnt162b2) is higly dependent to bone marrow plasmacytosis: long follow-up of symptomatic multiple myeloma patients

Background: SARS-COV-2 anti-Spike IgG response following mRNA vaccination (BNT162b2) is suboptimal and highly variable in MM patients. Patients and Methods: We report here a single-institution retrospective analysis of 127 consecutive patients with symptomatic MM (71 males, 56 females), [median age 69.5 years (range 45-85)], 63 patients with untreated MM and 64 patients with MM refractory to one or more previous treatment lines. Myeloma therapies included PI+IMiD combos, IMiD-based regimens, PI-based regimens, anti-CD38 mAb-based therapies, antibody-drug conjugates (Belantamab Mafodotin monotherapy), dexamethasone and high dose melphalan. Anti-spike IgG antibody were detected also in 50 healthy volunteers. Patients with symptomatic MM and healthy controls received two dose of COVID-19 mRNA vaccine (Pfizer BioNTech) on days 1 and 21 between 29 April and 15 May 2021. Patients with prior history of SARS-CoV-2 were excluded from analysis. Quantitative determination of anti-spike S1/S2 IgG antibody was performed at 4 weeks from vaccination completion (LIAISON® SARS-COV-2 S1/S2 IgG, LIAISON®). It was previously established a threshold >15 AU/ml of anti-Spike IgG which was related to neutralizing activity of anti-SARS-COV-2 antibodies. Results: Sixty-five out of 127 patients were evaluable for response. Anti-spike IgG antibody were detected in 50/65 (76.9%) MM patients, defined as responders [177 AU/mL (range 26.4 – 1430)]. 23.1% of MM patients, defined as non-responders, failed to respond at two doses of COVID-19 mRNA vaccine [3.8 AU/mL (range 0.65 – 9.33)]. Seroprotection rate at cutoff of 15 AU/mL was 100% in controls [249 AU/mL (range 104 - 2430)]. No statistically significant differences were found between the two subgroups of patients for myeloma disease phase (relapse/refractory MM vs. untreated symptomatic MM), LDH, residual gammaglobulin levels, WBC, ANC, lymphocytic response, age and sex (Tab. 2). Conversely, plasmacytosis, B2M and haemoglobin concentration were associated with a different response to vaccine. Patients with extreme plasmacytosis (60.0 ± 20.3 vs. 28.2 ± 18.8 mean ± SD; p <0.001) (Tab. 2) had a mean titer less than 15 AU/ml of anti-Spike IgG compared with patients with a low plasmacytosis, who, conversely, showed significantly higher mean titers of anti-Spike IgG. B2M was significantly higher in non-responders compared to responders (4.6 ± 4.1 vs. 3.2 ± 3.6 mean ± SD; p = 0.006) (Tab. 2). Haemoglobin value was significantly lower in non-responders compared to responders (10.8 ± 1.8 vs. 12.1 ± 1.8 mean ± SD; p = 0.008) (Tab. 2). Multivariate analysis confirmed the bone marrow infiltration pattern and haemoglobin value as statistically significant variables. In addition, in the present cohort, the myeloma treatment, including high-dose melphalan and autologous stem cell transplantation, have not been associated with SARS-CoV-2 infection. Conclusions: In our experience, significant fraction of MM patients (23.1%) does not developed any detectable anti-Spike IgG after two dose of COVID-19 mRNA vaccine. Lack of IgG response associated with three statistically significant variables: extreme plasmacytosis, B2M, and haemoglobin concentration. In the subgroup of patients with good response to vaccine, after a median follow-up of 7 months from second dose of COVID-19 mRNA vaccine, no cases of COVID-19 occurred.