Presenter: James Davis, PharmD, BCOP, Medical University of South Carolina, Hollings Cancer Center, Charleston, SC
Co-Authors: Katelynn Granger, PharmD; Kiera Roubal, PharmD; Deidra Smith, PharmD; Kelly J. Gaffney, PharmD, BCOP; Mary McGann, PharmD, BCOP; Alyssa Cendagorta, PharmD; Aswani Thurlapati, MD; Amanda Herbst, PA-C; Lindsey Hendrickson, DNP; Hamza Hashmi, MD; Brian T. Hess, MD, Medical University of South Carolina, Hollings Cancer Center, Charleston, SC
BACKGROUND: Despite the use of COVID-19 mRNA vaccines, patients with hematologic malignancies who become infected with severe acute respiratory virus (SARS-CoV-2) have increased risks for morbidity and mortality as a result of a diminished immune response to vaccination, advanced age, the use of immunosuppressive therapies, and immunodeficiency.1-5 Pre-exposure prophylaxis with tixagevimab-cilgavimab (Evusheld) may be an alternative strategy to decrease the incidence and/or severity of COVID-19 in these patients.6,7
OBJECTIVE: To determine the real-world efficacy and incidence of COVID-19 breakthrough infections in patients with hematologic malignancy who are receiving pre-exposure prophylaxis with tixagevimab-cilgavimab.
METHOD: We retrospectively analyzed the medical records at our institution to define the incidence of COVID-19 infection in patients with hematologic malignancies who received pre-exposure prophylaxis with tixagevimab-cilgavimab from January 2022 to November 2022. COVID-19 infection was defined by confirmed positive SARS-CoV-2 polymerase chain reaction and/or rapid antigen testing.
RESULTS: At a median follow-up of 190 days (range 19-289), 351 patients received tixagevimab-cilgavimab. A total of 41 (11.7%) patients had a confirmed COVID-19 breakthrough infection at a median of 90 days (range 3-170) after the administration of tixagevimab-cilgavimab. There were 31 (76%) infections that occurred ≥30 days after the administration of tixagevimab-cilgavimab. Among infected patients, 21 (51%) were receiving active treatment at the time of infection. In all, 3 (8%), 10 (25%), and 1 (2%) infected patients had undergone an autologous stem-cell transplant, allogeneic stem-cell transplant, or CAR T-cell therapy, respectively. The median time from transplant to infection was 135 days (range, 32-842 days), with 4 (10%) infections occurring before day 100 after the transplant. A total of 8 (20%) patients were hospitalized for severe infections, and 2 COVID-19–related deaths were observed. The majority (61%) of infected patients had received ≥3 previous COVID-19 vaccinations. Overall, tixagevimab-cilgavimab was well-tolerated, with 2 patients having low-grade adverse reactions, including diarrhea and rash.
CONCLUSION: Patients with hematologic malignancies are at risk for breakthrough infections, despite the use of pre-exposure prophylaxis with tixagevimab-cilgavimab, although it should be emphasized that hospitalization and mortality rates were low. Our findings suggest that these patients should maintain a multimodal prevention strategy, including social distancing, vaccination, and treatment with tixagevimab-cilgavimab.
- Vijenthira A, Gong IY, Fox TA, et al. Outcomes of patients with hematologic malignancies and COVID-19: a systematic review and meta-analysis of 3377 patients. Blood. 2020;136:2881-2892.
- Mato AR, Roeker LE, Lamanna N, et al. Outcomes of COVID-19 in patients with CLL: a multicenter international experience. Blood. 2020;136:1134-1143.
- Scarfò L, Chatzikonstantinou T, Rigolin GM, et al. COVID-19 severity and mortality in patients with chronic lymphocytic leukemia: a joint study by ERIC, the European Research Initiative on CLL, and CLL Campus. Leukemia. 2020;34:2354-2363.
- Pagano L, Salmanton-García J, Marchesi F, et al. COVID-19 in vaccinated adult patients with hematological malignancies: preliminary results from EPICOVIDEHA. Blood. 2022;139:1588-1592.
- Roeker LE, Knorr DA, Thompson MC, et al. COVID-19 vaccine efficacy in patients with chronic lymphocytic leukemia. Leukemia. 2021;35:2703-2705.
- Evusheld. Fact sheet for healthcare providers: emergency use authorization for Evusheld (tixagevimab co-packaged with cilgavimab). AstraZeneca Pharmaceuticals, LP; 2022.
- Levin MJ, Ustianowski A, De Wit S, et al. Intramuscular AZD7442 (tixagevimab-cilgavimab) for prevention of Covid-19. N Engl J Med. 2022;386:2188-2200.