P-030: Low infection rates in patients (pts) with relapsed/refractory myeloma (RRMM) treated with alnuctamab (ALNUC) in a setting of infection reduction strategies (IRS) and less frequent dosing

Introduction: Treatment with BCMA T-cell engagers (TCEs) increases infection risk. ALNUC is an IV or subcutaneously (SC) dosed TCE with bivalent BCMA binding and head-to-tail structure. SC ALNUC has shown a low rate of grade (G) ≥3 infections in a phase 1 study (NCT03486067) in pts with RRMM (Bar N et al. ASH. 2023). We hypothesized that less frequent dosing in later cycles and IRS implementation are associated with lower infection risk.

Methods: Pts had ≥3 prior therapy lines and were triple-class exposed. IV ALNUC (0.15–10 mg doses; enrolled 2018–2021) and SC ALNUC (3–60 mg doses; enrolled 2021–2023) were given QW in cycle (C) 1–3 (after step-up doses, if used), Q2W in C4–6, and Q4W in C7+ (28-d cycles). IRS were implemented in IV cohorts after March 2020 in response to G≥3 infections and in SC cohorts for entire duration. IRS included exclusion of pts with respiratory viruses and prophylaxis against bacteria (eg, levofloxacin; C1–3 and during G≥3 neutropenia), Pneumocystis (eg, trimethoprim-sulfamethoxazole; all Cs), and HSV/VZV (eg, acyclovir; all Cs). ALNUC was held for infections until recovery (G≤1/baseline). Immunoglobulin (Ig) levels were measured every C; Ig replacement therapy (IRT) was recommended for IgG < 400 mg/dL. Peripheral blood immune parameters were measured by flow cytometry. Correlations between baseline features and infections were assessed using 2-sided Wilcoxon test. Data cutoff was 4-Sep-2023.

Results: Of 70 pts who received IV ALNUC (median follow-up [MFU], 8 months), infections (any-G/G3–4/G5) occurred in 66%/36%/4%; 1 G5 event each of pneumonia, bacterial respiratory tract infection, and sepsis. Infection rates were reduced in the 39% of pts who enrolled after IRS implementation (56%/26%/0%) vs 61% of pts who enrolled prior (72%/42%/7%). There were no reported COVID-19 infections prior to IRS implementation; 5 pts (7%) had a COVID-19 event.

Of 78 pts who received SC ALNUC (MFU, 12 months), infection rates (any-G/G3–4/G5) were 59%/17%/1%; 1 G5 influenza event occurred. Opportunistic infections (4%) included cytomegalovirus reactivation (3%; n=2, both G2 and no organ involvement) and fungal esophagitis (1%; n=1, G1). COVID-19 events occurred in 24% of pts. IgG < 400 mg/dL occurred in 56% of pts (≥1 events) and was more common in pts with than without G≥3 infections, particularly in later cycles (64% vs 35% at C4D1). IRT was used in 41% of pts. Rate of G≥3 infections decreased over time; 7.8% in C1–3, 7.5% in C4–6, 8.8% in C7–9, 6.5% in C10–12, 3.8% in C13–15, and 0% in C16+. Baseline pt factors (eg, disease burden, baseline labs, and immunophenotyping data) were not found to be associated with on-treatment G≥3 infections among pts who received SC ALNUC.

Conclusions: These data suggest that aggressive IRS, IRT, and reduced dosing frequency of ALNUC in later cycles contributed to successful reduction of infection rates. Additional immunologic analyses are ongoing to determine the relationship between low infection rates and the unique bivalent format/schedule of ALNUC.