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e19517 Background: Although immunotherapy shows favorable survival outcomes among heavily pretreated relapsed/refractory multiple myeloma (RRMM) patients, infections are a common cause of morbidity and mortality that are not well characterized in this patient population. The goal of this study was to estimate the incidence of infections from clinical trials of treatments for RRMM by grade, infection type, and treatment received. Methods: We conducted a literature search in EMBASE, PubMed, Cochrane, approval packages and labeling, and conference proceedings to identify phase 2-3 clinical trials of single drug interventions published prior to 18 June 2023 with data on infections. We included studies of patients aged ≥18 years who received prior MM treatment with an immunomodulatory agent, protease inhibitor, and anti-CD38 antibody. A Bayesian meta-analysis accounting for left-censored data was used to estimate the pooled incidence of infection from the studies by infection type (upper respiratory tract infection uRTI, sepsis, bacteremia, pneumonia, SARS-COV-2, and bacterial and viral infections), grade (all, grades ≥3, and 5/fatal) and type of treatment received (antibody and CAR-T). Results: Nine studies (7 phase 2, 1 phase 3 and 1 product label) of seven compounds (1 selective inhibitor of nuclear export, 2 CAR-T, and 4 monoclonal and bispecific antibodies) were identified and are/were approved in the US for RRMM treatment. All included articles were published after July 2019 on treatments approved since 2020 for patients who had received ≥4 prior lines of therapy. They included a total of 1,141 patients (median follow-up 10.1 - 23 months). The pooled incidence of all infections was 61.6% (95% credible interval, 58.6%-64.6%), 28.7% (24.7%-32.2%) and 4.1% (2.9%-5.6%) for all-grades, grades ≥3, and 5 respectively. uRTI was the most common type of all-grade infection (22.8% 20.0%-25.6%) while SARS-COV-2 (6.8% 4.9%-9.4%) and pneumonia (6.8% 5.0%-9.1%) were the most common grade ≥3 infections. Sepsis was the most common fatal infection (1.0% 0.4%-1.8%). Patients treated with monoclonal/bispecific antibodies had a slightly higher incidence of all-grade infections (64.2% 60.4%-67.9%) compared to CAR-T (58.6% 52.8%-64.2%). The incidences for these treatments were similar for grades ≥3 (28.9% vs 28.2%) and 5 (3.5% vs 4.5%) infections. Conclusions: In clinical trials of treatment for triple class exposed RRMM, the incidence of infection was high, including grade 3 or higher infections. A large proportion of grade ≥3 infections were attributable to SARS-COV-2 and pneumonia, with sepsis as the most common fatal infection. The incidence of grade ≥3 infection was generally consistent for CAR-T and monoclonal/bispecific antibody therapy.
Omofuma et al. (Sat,) studied this question.