P-042: Early infections in myeloma patients treated with anti-BCMA bispecific antibodies.

Introduction: Myeloma patients treated with anti-BCMA bispecific antibodies (bsAb) are at high risk of developing infections due to subsequent depletion of immunoglobulins (IG) and T cell exhaustion. Preventive measures include IG replacement, but no firm recommendations about timing and target levels exist. We aimed to describe early infection incidence, severity, and IgG levels in patients treated with anti-BCMA bsAb.

Methods: We retrospectively analyzed patients who received at least one cycle of anti-BCMA bsAB therapy. The parameters of interest included: infection occurrence, onset time of infection, severity, source of infection, microbiological documentation of infection, IgG levels before treatment and after treatment initiation within 30-60 days where available. Infections were graded per CTCAE v 5.0.

Results: Overall, 32 patients were included in the analysis. Patients received median 0 prior lines of therapy (range 0-4). 29 patients (90,7%) received anti-BCMA as monotherapy, 3 patients (9,3%) as combination with antiCD38 antibody. Overall, 15 patients (47%) of patients experienced an infectious episode within the observation period, 5 (16%) grade 2, 7 (22%) grade 3, 2 (6%) grade 4 and 1 (3%) grade 5. All but one were respiratory tract infections, one was CMV reactivation. Out of 7 microbiologically documented infections, 6 were COVID-19 (omicron era) and one CMV. No patient received IG replacement therapy before the infection onset and 9/15 (60%) patients received IG after an infectious episode. IgG levels before and after treatment were available in 24 patients. One patient had IgG levels below 4 g/L before treatment initiation, whereas 17 (70.8%) patients had IgG below 4 g/L within the first 60 days of treatment initiation.

Conclusions: Early onset infections are frequent and early IgG drop is present in the majority of patients. Early immunoglobulin replacement should be adopted as a preferable strategy. The possibility of preemptive IG replacement should be evaluated in a prospective manner. COVID-19 remains a significant source of morbidity in patients treated with anti-BCMA bsAb.