(066) Incidence of Infections in Clinical Trials of Treatments for Relapsed/Refractory Multiple Myeloma: Systematic Review and Meta-Analysis

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 and are not well characterized in this patient population.

Objectives: To estimate the incidence of infections from clinical trials of treatments for triple-class exposed (TCE) RRMM by grade and infection type.

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 minimum reporting thresholds 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) and grade (all, grades ≥3, and 5/fatal).

Results: Ten studies (6 phase 2, 1 phase 3, 1 product label and 2 assessment reports) of seven compounds (1 SINE, 2 CAR-T, 1 antibody drug conjugate and 3 bispecific antibodies (2 BCMA x CD3 and 1 GPRC5D x CD3) 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 ranged from 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%]), which was reported in 4 of the compounds, and pneumonia (6.8% [5.0%-9.1%]) were the most common grade ≥3 infections. Sepsis was the most common fatal infection (1.7% [1.3%-2.8%]).

Conclusions: In clinical trials of treatment for TCE RRMM, infections occurred in 61.6% of patients and the incidence of grade 3 or higher infections was 28.7%. A large proportion of grade ≥3 infections were attributable to SARS-COV-2 and pneumonia, with sepsis as the most common fatal infection.