(OA-57) IVIG and Longer Dosing Intervals Reduce Risk of Infections in Patients with RRMM Treated with Teclistamab

Patients with relapsed/refractory multiple myeloma (RRMM) who are treated with BCMA-directed bispecific antibodies (BsAbs) are at increased risk of infections. Previous studies have shown that treatment with intravenous immunoglobulin (IVIG) reduces the risk for severe infections. However, whether IVIG also reduces all-grade infections and whether prolonging dosing intervals influences infection risk, remains unknown. To address this, we retrospectively investigated 80 patients who were treated with teclistamab.



Methods:

All patients with RRMM who were treated with teclistamab between 2019 and 2025 in Amsterdam University Medical Center in The Netherlands were included. Patients received cotrimoxazole and valaciclovir as antimicrobial prophylaxis. IVIG was prescribed as primary prophylaxis for infections when polyclonal IgG was < 4 g/L, or as secondary prophylaxis after a severe infection (CTC grade ≥3) with polyclonal IgG < 4 g/L, based on evolving clinical practice. Annualized infection rates were calculated for each patient by dividing the total number of infections by the total time on treatment and compared between patients who received IVIG and those who did not, using Poisson models. Associations between annualized infection rates and dosing schedules were assessed using negative binomial regression models.



Results:

Eighty patients with RRMM who received teclistamab were included in the study. Fifty-one patients (64%) participated in a clinical trial and 29 patients (36%) enrolled in a compassionate use program. Median age was 65 years (range 42 – 81). In total, 66/80 patients (83%) received IVIG supplementation, of whom 51 patients (77%) received IVIG as primary prophylaxis and 15 (23%) received IVIG after a severe infection.

After a median follow-up of 21 months, in total 390 infections were reported, of which 48 were severe. Treatment with IVIG resulted in significantly lower rates of both severe infections (0.33 versus 0.93 per patient-year, p< 0.001) as well as of all-grade infections (3.15 versus 4.41 per patient-year, p< 0.01). Older age and elevated beta-2-microglobulin were found to be independently associated with risk for severe breakthrough infections.

During weekly dosing, 6.08 all-grade infections occurred per patient-year (py). These numbers were 3.54/py during biweekly (p< 0.01), 2.93 during monthly (p< 0.01) and 2.25 during bimonthly dosing schedules (p< 0.001). Severe infection rates decreased from 0.81 per patient-year during weekly, to 0.39 during biweekly (p=0.19), 0.29 during monthly (p=0.07) and 0.1 during bimonthly dosing (p< 0.05). Importantly, a sensitivity analysis in 66 patients who received IVIG prophylaxis, revealed that a reduction in severe infections was still observed, when patients switched to longer dosing intervals.



Conclusions:

We here show for the first time that there is a benefit of longer dosing intervals for reducing the risk of severe infections during treatment with teclistamab, also in patients receiving IVIG supplementation.