People with hematologic malignancies (blood cancers), including leukemia, lymphoma, and multiple myeloma—have an impaired immune system due to their disease and its treatment, putting them at risk of severe COVID-19 infection and experiencing a reduced response to COVID-19 vaccination.[1]

About 2% of the global population is considered at increased risk of such an inadequate response to a COVID-19 vaccine. This includes aproximately seven million people in the US who are immunocompromised because of a diagnosis of a hematologic malignancy or other cancers being treated with chemotherapy, but also patients taking medications after an organ transplant or who are taking immunosuppressive drugs for conditions including multiple sclerosis and rheumatoid arthritis.[1]

In a recent study published online in CANCER, a peer-reviewed journal of the American Cancer Society, less than half of patients with hematologic malignancies mounted detectable antibodies after initial COVID-19 vaccination, but 56% of “nonresponders” produced antibodies after receiving a booster dose.[2]

For this study, Thomas Ollila, MD, of Brown University (Providence, RI), and his colleagues retrospectively analyzed antibody responses to initial and booster COVID-19 vaccination in 378 patients with hematologic malignancies.

Anti-SARS-CoV-2 antibodies were detected in the blood of 181 patients (48%) after initial vaccination with one of three U.S. Food and Drug Administration (FDA)-authorized or approved COVID-19 vaccines, and patients with active cancer or those recently treated with an immune cell–depleting therapy were least likely to produce these antibodies. Among patients who did not mount an antibody response following initial vaccination, responses were observed after a booster dose in 48 of 85 (56%) patients who were assessed.

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By the end of February 2022, 33 patients (8.8%) developed a COVID-19 infection, with three COVID-19-related deaths (0.8%). Although there was no significant link between post-vaccination antibody response and incidence of COVID-19 infection, no patient with antibody responses died from COVID-19.

Also, patient who received intramuscular monoclonal-antibody combination AZD7442 (tixagevimab plus cilgavimab; Evusheld®; AstraZeneca) were not diagnosed with a COVID-19 infection.

Tixagevimab (AZD8895) and cilgavimab (AZD1061) are antibody therapies derived from B-cells donated by convalescent patients after SARS-CoV-2 virus that bind to non-overlapping portions of the SARS-CoV-2 spike protein. This prevents the virus from binding to and infecting cells. Pharmacokinetic data in humans indicate that the combination of tixagevimab plus cilgavimab has an extended half-life of approximately 90 days. [3]

The FDA authorized the combination therapy for emergency use during the COVID-19 pandemic as a way to help prevent COVID-19 infection in certain individuals.

“Our findings build on the wealth of literature showing that patients with hematologic malignancies have an impaired response to COVID vaccination. Importantly, we show that many of these patients who did not respond initially will in fact have a response to booster vaccination,” Ollila said.

“Moreover, when we looked at outcomes, we found that deaths from COVID-19 in the patient population we reviewed only occurred in those with undetectable antibodies, and nobody who received prophylactic antibody therapy was diagnosed with COVID-19. This suggests to us the importance of checking antibody levels in these patients and arranging prophylactic antibody therapy,” he added.

Ollila encourages providing booster vaccines for patients and prioritizing prophylactic antibody therapy when indicated.

“This is real world evidence that these actions can save lives,” he concluded.

[1] Oliver, S. Data and clinical considerations for additional doses in immunocompromised people. ACIP Meeting July 22, 2021. CDC. Online.  Last accesses on July 7. 2022.
[2] Ollila TA, Masel RH, Reagan JL, Lu S, Rogers RD, Paiva KJ, Taher R, Burguera-Couce E, Zayac AS, Yakirevich I, Niroula R, Barth P, Olszewski AJ. Seroconversion and outcomes after initial and booster COVID-19 vaccination in adults with hematologic malignancies. CANCER; Published Online: July 11, 2022 (DOI: 10.1002/cncr.34354).
[2] Levin MJ, Ustianowski A, De Wit S, Launay O, Avila M, Templeton A, Yuan Y, Seegobin S, Ellery A, Levinson DJ, Ambery P, Arends RH, Beavon R, Dey K, Garbes P, Kelly EJ, Koh GCKW, Near KA, Padilla KW, Psachoulia K, Sharbaugh A, Streicher K, Pangalos MN, Esser MT; PROVENT Study Group. Intramuscular AZD7442 (Tixagevimab-Cilgavimab) for Prevention of Covid-19. N Engl J Med. 2022 Jun 9;386(23):2188-2200. doi: 10.1056/NEJMoa2116620. Epub 2022 Apr 20. PMID: 35443106; PMCID: PMC9069994.

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