TECVAYLI - Impact of Primary Immunoglobulin Prophylaxis on Infections

SUMMARY  

• Johnson & Johnson does not recommend the use of TECVAYLI in a manner inconsistent with the approved labeling.
• The information presented below is limited to evaluations of primary intravenous immunoglobulin (IVIG) prophylaxis compared with patients who received no IVIG prophylaxis and infection outcomes.

Clinical Data

• MajesTEC-1 is a phase 1/2, multicohort study evaluating the safety and efficacy of TECVAYLI in patients with relapsed or refractory multiple myeloma (RRMM).¹
  • Frerichs et al (2024)² evaluated the impact of IVIG supplementation on the frequency of severe infections in 52 patients treated with TECVAYLI in the MajesTEC-1 study at Amsterdam University Medical Center.
    • Primary IVIG prophylaxis referred to preemptive IVIG replacement in patients with polyclonal immunoglobulin G (IgG) <4 g/L. Secondary IVIG prophylaxis was administered at the physician’s discretion in patients who developed a severe infection with IgG <4g/L. Primary IVIG supplementation was administered to 20 patients. None of these patients discontinued IVIG while on TECVAYLI. IVIG as secondary prophylaxis was administered to 32 patients (observation group).
    • The incidence rate of infections was 0.12 per patient-year (95% confidence interval [CI], 0.014-0.42) in the primary IVIG prophylaxis group, compared to 1.36 per patient-year (95% CI, 0.84-2.03) in the observation group (incidence rate ratio, 11.6; 95% CI, 2.70-50.0; P=0.001). The cumulative incidence of serious infections at 6 months was 5.3% in the primary IVIG prophylaxis group and 54.8% in the observation group (P<0.001).
    • A total of 2 serious infections in 2 patients occurred during 204.5 months of IVIG treatment, compared to 20 infections in 18 patients not receiving IVIG during 176.8 months of observation. The most common type of grade ≥3 infections in the observation group were lower respiratory tract infections, accounting for 13 of 20 infections (65%).
    • Fourteen of the 18 patients in the observation group who developed a serious infection were subsequently administered IVIG (secondary prophylaxis). During 144.8 months of follow-up, 1 of these patients developed a serious infection after IVIG was initiated (incidence rate, 0.083 per patient-year; 95% CI, 0.0021-0.45). This was significantly lower than what was observed in the absence of IVIG supplementation (incidence rate ratio, 16.4; 95% CI, 2.22-125; P=0.006). Of the remaining 4 patients who were not initiated on IVIG, 3 patients died as a result of infection, and 1 patient discontinued study due to disease progression.
    • After 6 months, the cumulative frequency of serious infections after initiation of secondary IVIG prophylaxis was 0%.

additional Data

Smits et al (2026)³ published results from a retrospective, single-center cohort study evaluating infection incidence and the impact of IVIG prophylaxis in patients with RRMM treated with TECVAYLI.

This section presents the overall incidence of infections and outcomes associated with primary infection prophylaxis.

Study Design/Methods

• Patients initiated TECVAYLI at the Amsterdam University Medical Center in the Netherlands between January 2019 and December 2024.
• Polyclonal IgG levels were assessed at baseline and monitored monthly throughout treatment. In patients with IgG myeloma, the M-spike component was subtracted from total IgG levels to estimate polyclonal IgG levels.
• IVIG was administered as primary prophylaxis for infections in patients with polyclonal IgG <4 g/L or as secondary prophylaxis following a severe infection (Common Terminology Criteria for Adverse Events grade ≥3) in patients with polyclonal IgG <4 g/L.
• IVIG was administered every 4 weeks, on the same day as TECVAYLI, at an initial dose of 10-20 g; doses were subsequently adjusted to maintain polyclonal IgG levels >4 g/L.
• IVIG treatment was continued throughout TECVAYLI therapy and, in patients who discontinued TECVAYLI, for at least 6 months after the last TECVAYLI administration.
• Patients received standard antimicrobial prophylaxis with cotrimoxazole (or pentamidine in case of allergy) and valaciclovir; no other antibacterial or antifungal prophylaxis was administered.

Results

Patient Characteristics

• Among 80 patients with RRMM, 64% (n=51) participated in a clinical trial and 36% (n=29) were treated through a compassionate use program.
• High disease stage (International Staging System III) was present in 17% of patients, 39% had high-risk cytogenetic abnormalities, 23% had extramedullary disease, and 56% were triple-class refractory. Patients received a median of 5 prior lines of therapy.
• A total of 83% of patients (n=66) received IVIG supplementation, including 51 patients who received IVIG as primary prophylaxis.
• The median time to initiation of IVIG as primary prophylaxis was 1.11 months.

Efficacy

• At a median follow-up of 21 months, median progression-free survival (PFS) was 18.1 months (95% CI, 11.8-37.6) and median overall survival (OS) was 43.5 months (95% CI, 24.6-not estimable [NE]).

Safety

IVIG-Related Reactions

• Infusion-related reactions associated with IVIG were reported in 10/66 patients (15%):
  • Grade 1 reactions accounted for 30% of events and were managed by interrupting the infusion and resuming administration at a slower rate.
  • Grade 2 reactions accounted for 70% of events; these patients also received prednisolone and clemastine.
  • Patients with grade 2 reactions subsequently received prednisolone 25 mg and clemastine 1-2 mg prophylactically before future IVIG infusions.

Overall Incidence of Infections and Impact of Primary IVIG Prophylaxis

• At a median follow-up of 21 months, 72/80 patients (90%) experienced ≥1 infection and 30/80 patients (38%) experienced ≥1 severe infection (grade ≥3).
• Four patients (5%) died due to infection; all infection-related deaths were attributed to pneumosepsis, and 3 of the 4 patients had not received IVIG supplementation.
• The median time to first infection was 1.3 months and the median time to first severe infection was 6.5 months.
• Overall, 390 infections were reported, of which 48 (12%) were severe. Annualized rates were 3.81 all-grade infections and 0.47 severe infections per patient-year.
• The cumulative incidence of severe infections was significantly lower among patients receiving primary IVIG prophylaxis (P<0.001).
• No difference in cumulative incidence of all-grade infections was observed between patients who received primary IVIG prophylaxis and those who did not receive primary IVIG prophylaxis (P=0.99).

Infection Characteristics

• Respiratory infections represented the most common infections, accounting for 316 of 390 infections (81%), while gastrointestinal infections accounted for 43 infections (11%).
• Infection type distribution was comparable between patients who received IVIG and those who did not receive IVIG; respiratory infections represented 80% and 84% of infections, respectively.
• All reported opportunistic infections occurred during IVIG supplementation, except for Pneumocystis jirovecii pneumonia.

Mohan et al (2025)⁴ presented results from a multi-institutional study evaluating the effect of primary IVIG replacement (n=92) compared with no primary IVIG prophylaxis (n=133) in patients with RRMM who received at least one dose of TECVAYLI or an investigational B-cell maturation antigen (BCMA)-directed bispecific antibody (BsAb). 

• Primary IVIG prophylaxis was administered following the start of BsAb therapy and prior to a documented infection, whereas secondary IVIG prophylaxis was administered following a documented infection. In patients who received TECVAYLI, 78 patients received primary IVIG prophylaxis while 82 patients received no primary IVIG prophylaxis.
• Treatment groups were pooled, and results were provided for spectrum of infections, infection-free survival and PFS/OS and IVIG prophylaxis.

Mohan et al (2024)⁵ conducted a retrospective cohort study on the efficacy and safety of TECVAYLI in 110 patients with RRMM across 5 United States (US) academic centers from January 2023 to August 2023.

• Primary IVIG prophylaxis referred to preemptive IVIG replacement given in patients with hypogammaglobulinemia, regardless of any history of infection. IVIG supplementation was administered to 43% of patients (n=46) as primary prophylaxis.
• Overall, 78 infections were diagnosed in 44 patients; all grades and grade ≥3 infections were 40% (n=44) and 26% (n=29), respectively. Recipients of IVIG had a statistically significant reduction in rates of all grades (0.95 vs 0.45; P=0.005) and grade ≥3 infections (0.61 vs 0.24; P=0.011) per 100 days compared to patients who did not receive IVIG supplementation.
• The cumulative incidence of infections (all grades) at 3 and 6 months in patients who received primary IVIG supplementation was 35% (95% CI, 23-55) and 35% (95% CI, 23-55), respectively, compared with 44% (95% CI, 33-60) and 54% (95% CI, 41-71), respectively, in patients who did not receive IVIG supplementation. The cumulative incidence of grade ≥3 infections at 3 and 6 months in patients who received primary IVIG supplementation was 17% (95% CI, 8.7-35) each, compared to 31% (95% CI, 21-46) and 43% (95% CI, 31-61) respectively, in patients who did not receive primary IVIG prophylaxis.

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File databases (and/or other resources, including internal/external databases) was conducted on 09 September 2026.