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Study Proposes Recommendations for Infections During Teclistamab Treatment of R/R MM

February 2, 2024

February 2024

Katie Robinson

Katie Robinson is a medical writer based in New York.

When using teclistamab to treat patients with relapsed or refractory (R/R) multiple myeloma (MM), clinicians should remain vigilant for a range of infection types and undertake appropriate screening, prophylaxis, and management of infections, hypogammaglobulinemia, and neutropenia. This is according to an analysis, published in Cancer, of the phase I/II MajesTEC-1 study, which examined infections during treatment with the B-cell maturation antigen-directed bispecific antibody that is approved for the treatment of triple-class-exposed R/R MM.1

“Based on this experience, the recommendations for safer administration of teclistimab include up-to-date vaccinations, including COVID-19, screenings for hepatitis B and C and HIV, and initiating viral suppressive therapy as indicated,” said corresponding author Ajay K. Nooka, MD, MPH, of the Winship Cancer Institute at Emory University School of Medicine in Atlanta. “Teclistamab should not be initiated in patients with any active infections.”

In the MajesTEC-1 study, 165 patients (median age = 64; 58.2% male) with R/R MM were enrolled between March 2020 and August 2021. They received subcutaneous teclistamab 1.5 mg/kg weekly after a step-up dosing schedule, with an option to extend the dosing interval to biweekly or monthly after the first six months of therapy. Patients were monitored for infections frequently, while prophylaxis and management followed institutional guidelines.1,2

At a median follow-up of 22.8 months, infections were reported in 80.0% of the patients, with grade 3 or 4 infections occurring in 55.2%. The median time to first onset of infection was 1.7 months for any grade infection and 4.2 months for those of grade 3 or greater.1

“A decrease in new-onset infections of grade 3 or above over time was observed, specifically, after 12 months of teclistamab treatment. This was more evident among patients who switched to biweekly teclistamab by one year compared with those who remained on weekly dosing,” Dr. Nooka explained.

The most common grade 3 or higher infections were COVID-19 (21.2%) or respiratory infections (19.4%), followed by Pneumocystis jirovecii pneumonia (PJP; 4.2%), viral infections (4.2%), and gastrointestinal infections (1.2%). Twenty-one patients (12.7%) died from infections, of which 18 deaths were from COVID-19.

“Unfortunately, there were no COVID-19 vaccines available until nine months after enrollment for MajesTEC-1 had started. Very few patients had therefore been vaccinated before starting teclistamab, and the study population may have been particularly vulnerable to COVID-19 infection, which also explains why these occurred throughout the study as the enrollment period for MajesTEC-1 overlapped with the COVID-19 pandemic,” Dr. Nooka said. “Adding to this, very few published guidelines existed on the prevention and management of infections with bispecific antibodies at the time of peak enrollment.”

Overall, 70.9% of patients had one or more post-baseline immunoglobulin G (IgG) levels below 400 mg/dL. The median time to hypogammaglobulinemia was 1.2 months, and 46.1% received at least one dose of IgG replacement. Neutropenia occurred in 71% of patients, with grade 3 or higher occurring in 65%. The peak incidence of neutropenia was observed at 2.3 months after starting teclistimab.

“Over half of the patients received granulocyte colony-stimulating factor (GCSF), beyond the step-up dosing schedule when the risk of cytokine release syndrome is minimized,” Dr. Nooka said. “Usage of GCSF for grade 3 neutropenia with infection or fever and grade 4 neutropenia and intravenous IgG replacements for IgG levels below 400 mg/dL during teclistamab treatment is crucial in minimizing the risk of higher-grade infections.

“Prophylaxis for PJP, herpes simplex virus, and varicella zoster virus should be given to all patients during teclistamab treatment,” Dr. Nooka said. “Other prophylactic antimicrobials should be administered based on patient risk factors and institutional guidelines.”

The authors noted that the single-arm trial of heavily pretreated patients did not enable the impact of teclistamab on infections to be differentiated from the effects of previous therapies, prior relapses, or MM. Another limitation was the varied treatment practices across institutions involved in the study.

Any conflicts of interest declared by the authors can be found in the original article.

References

  1. Nooka AK, Rodriguez C, Mateos MV, et al. Incidence, timing, and management of infections in patients receiving teclistamab for the treatment of relapsed/refractory multiple myeloma in the MajesTEC-1 study. Cancer [published online ahead of print, 2023 Nov 14]. doi: 1002/cncr.35107.
  2. Moreau P, Garfall AL, van de Donk NWCJ, et al. Teclistamab in relapsed or refractory multiple myeloma. N Engl J Med. 2022;387(6):495-505.

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