NCCN Guidelines Now Recommend Pemivibart for COVID-19 Prevention in B-Cell Lymphomas

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The National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology have added the investigational monoclonal antibody pemivibart (Pemgarda; VYD222) for B-cell lymphomas.1

Alongside the Infectious Disease Society of America (IDSA), which updated its COVID-19 guidelines in 2024, the NCCN recommends the use of pemivibart for pre-exposure prophylaxis (PrEP) in adult and adolescent (12 years of age or older) patients who are moderately to severely immunocompromised and are at risk for progression to severe COVID-19 variants that are susceptible to pemivibart. Of note, the NCCN’s inclusion of pemivibart poses the agent as a potential treatment for PrEP against COVID-19, particularly in patients with B-cell malignancies who may not have an optimal immune response to vaccination.

“We are honored that NCCN has acknowledged the role of pemivibart in helping protect one of the most vulnerable patient populations—those with compromised immune systems due to B-cell lymphomas—especially in light of ongoing COVID-19 threats,” Tim Lee, chief commercial officer at Invivyd, the developer of pemivibart, stated in a news release. “This recognition reflects the growing confidence in the therapeutic potential of pemivibart, and reinforces our commitment to immunocompromised patients, including those facing difficult to treat lymphomas, particularly as COVID-19 remains a year-round threat, with another surge expected this summer.”

The NCCN’s recommendation for pemivibart was due to persisting unmet needs in patients with B-cell lymphomas, specifically as this patient population is at higher risk for COVID-19–related complications. Notably, pemivibart is a monoclonal antibody against SARS-CoV-2 variants, which is also authorized under Emergency Use Authorization from the FDA for PrEP of COVID-19.

The phase 3 CANOPY trial (NCT06039449) evaluated pemivibart to prevent COVID-19 in immunocompromised patients at higher risk of exposure.2 Patients on the study were at least 18 years of age and did not have SARS-CoV-2 infection at enrollment. In cohort A, patients were significantly immunocompromised due to solid tumors or hematologic malignancies, CAR T-cell therapy or hematopoietic stem cell transplantation, primary immunodeficiency, advanced HIV infection, or qualifying immunosuppressive therapies.3 Those in cohort B were at risk of contracting SARS-CoV-2 following indoor face-to-face interactions without adequate masking. Patients were randomly assigned 2:1 to be treated with blinded pemivibart or placebo (cohort B) 90 days apart.2 From September to November 2023, patients from cohort A were treated with pemivibart (n = 306); those in cohort B were either treated with pemivibart (n = 317) or placebo (n = 162). Patients in cohort A were treated with 2 intravenous infusions of pemivibart at 4500 mg. Additionally, those in cohort B were either treated with the same dose of pemivibart or placebo. The primary end point was safety; exploratory end points included the composite incidence of reverse transcription–polymerase chain reaction–confirmed symptomatic COVID-19, hospitalization due to COVID-19, and all-cause mortality.

The most common treatment-related adverse effect was infusion-related reactions (cohort A, 3.6%; cohort B, 2.2%; placebo, 0%). Of note, 4 patients in the overall population treated with pemivibart experienced anaphylactic reactions, 2 of which were deemed serious.

“Managing B-cell lymphoma is inherently challenging for patients, and the added risk of severe COVID-19 further complicates their care,” George Yaghmour, MD, assistant professor of clinical medicine at Keck Medicine of the University of Southern California, said in the news release.1 “The inclusion of pemivibart in the NCCN Guidelines is an important development, providing clinicians with a valuable tool to guide treatment decisions. It helps protect vulnerable patients from COVID-19, allowing them to stay out of the hospital, continue their cancer care, and focus on their recovery.”

References

1. Invivyd announces inclusion of Pemgarda (pemivibart) in National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology for B-cell lymphomas. News release. Invivyd. May 23, 2025. Accessed May 28, 2025. https://investors.invivyd.com/news-releases/news-release-details/invivyd-announces-inclusion-pemgardar-pemivibart-national
2. Wolfe CR, Cohen J, Mahoney K, et al. Safety and efficacy of pemivibart, a long-acting monoclonal antibody, for prevention of symptomatic COVID-19: interim results from a phase 3 randomized clinical trial (CANOPY). Clin Infect Dis. Published online May 24, 2025. doi:10.1093/cid/ciaf265
3. A study to investigate the prevention of COVID-19 with VYD222 in adults with immune compromise and in participants aged 12 years or older who are at risk of exposure to SARS-CoV-2. ClinicalTrials.gov. Updated December 9, 2024. Accessed May 28, 2025. https://clinicaltrials.gov/study/NCT06039449