(OA-20) Temporal Trends in Infectious Risk Among Multiple Myeloma Patients Treated with Daratumumab: A Meta-Analysis

Multiple myeloma (MM) is associated with a significant infectious risk, particularly among patients treated with the anti-CD38 monoclonal antibody (mAb), daratumumab. The design of infectious prophylaxis studies requires granular characterization of infection risk over time, something missing from clinical trial reports. We aimed to characterize the nature, frequency and timing of infections in patients with daratumumab (dara) vs non-daratumumab (non-dara) regimens.

Methods:

We performed an individual patient-level meta-analysis of adverse event (AE) data for phase 2 or 3 randomized clinical trials shared on the Yale Open Access Data (YODA) repository. Included trials compared dara vs non-dara regimens (NDMM trials: MAIA, ALCYONE, GRIFFIN; RRMM trials: POLLUX, CASTOR, and APOLLO). Infectious AE terms were grouped to determine organ involvement, type of pathogen, and severity (CTCAE grading). For patients treated on the GRIFFIN trial, infectious complications within 90 days post autologous transplant were excluded. The primary outcome was to characterize the proportion of patients followed in each 3-month (quarter, Q) with a grade ≥1 infection, for up to 2 years after treatment initiation.

Results: In total, 2,989 clinical trial patients were included in this analysis (1,500 Dara patients; 1,489 non-Dara patients). Baseline characteristics—including age, performance status, ISS stage, and baseline neutrophil count—were similar between patients who experienced grade 1–2 versus grade 3–5 infections in both the Dara and non-Dara cohorts. Overall, 1,178 (79%) Dara patients and 914 (61%) non-Dara patients experienced an infectious AE within 2 years of treatment. Grade ≥3 infections occurred in 436 (29%) Dara patients and 301 (20%) non-Dara patients. Multiple grade 0–2 infections were observed in 753 (50%) Dara patients and 452 (30%) non-Dara patients, while multiple grade ≥3 infections occurred in 167 (11%) and 101 (7%) patients, respectively.

The proportion of Dara-treated patients with infections of any grade was 42.2% in Q1, plateauing at 22.8–28% from Q3–Q8. The corresponding proportions for non-Dara–treated patients were 36.2% in Q1 and 17.8–21.9% from Q2–Q8. The incidence of grade ≥3 infections in Dara-treated patients was 13.1% (Q1), 5.9% (Q2), and 3.1–4.6% (Q3–Q8), compared to 9.8% (Q1) and 3.2–4.0% (Q2–Q8) in non-Dara patients.

Conclusions:

This is the first study to characterize infection risk over time in Dara-treated patients. Infectious risk is higher in dara-treated patients, mostly due to grade 1-2 events. Regardless of treatment, risk of infection is highest in the first 3 months, reaching a plateau in the second quarter and beyond, highlighting the contribution of disease burden to immune deficiency. These findings clarify anti-CD38 mAb toxicity and may guide prophylaxis strategies by identifying the early period as highest risk. An in-depth analysis by line of therapy, patient and disease characteristics and type of infection will be presented at the meeting.