The evolution of the SARS-CoV-2 virus has presented ongoing challenges in the prevention and treatment of COVID-19, particularly since omicron and its subvariants began to emerge.
Vaccine development has not kept pace with the emergence of new variants, and monoclonal antibodies (mAbs) that were previously used for COVID-19 prevention and treatment are ineffective against the omicron subvariants currently in circulation.
These developments are especially concerning for patients who are moderately to severely immunocompromised and thus at higher risk for more severe and lasting symptoms, hospitalization, and death due to COVID-19.1
Many cancer patients are included in that group, noted Julie Gralow, MD, chief medical officer and executive vice president of the American Society of Clinical Oncology (ASCO).
“Patients with hematologic malignancies, those with solid tumors on active cytotoxic chemotherapy or certain immunosuppressive or immunomodulatory biologic agents, those who have undergone stem cell or bone marrow transplant — and may remain on immunosuppressive drugs — and those on high doses of corticosteroids meet the CDC’s definition of moderately to severely immunocompromised,” Dr Gralow explained.
Methods of preventing and treating COVID-19 in these vulnerable patients have had to evolve alongside the SARS-CoV-2 virus.
Vaccine Efficacy May Vary, Vaccination Still Recommended
Even before the original omicron variant (BA.1) emerged, studies suggested that cancer patients did not always mount an adequate response to COVID-19 vaccination, and the risk of breakthrough COVID-19 and death was higher in cancer patients than in the general population.2-6
Breakthrough COVID-19 was found to be even more common in cancer patients after omicron emerged, and recent research suggests cancer patients still have a higher risk of breakthrough COVID-19, hospitalization, and death than the general population.7,8
Some recent studies in the general population have suggested that the bivalent mRNA vaccines can provide better protection against omicron subvariants than monovalent mRNA vaccines.9-11 Other studies have suggested that bivalent vaccines may be no more effective than monovalent vaccines against the currently circulating omicron subvariants.12-15
Data showing the effects of the bivalent vaccines in cancer patients are limited. One small study suggested that Pfizer-BioNTech’s bivalent vaccine increased virus-neutralizing capacity against the BQ.1.1 subvariant but not against the XBB.1 and XBB.1.5 subvariants.16
Although the antibody response to vaccination may be suboptimal in immunocompromised patients, the “vaccines have the advantage of stimulating multiple arms of the immune system, which likely still offers some degree of protection, even with omicron subvariants,” according to Amy Sherman, MD, instructor at Harvard Medical School, associate physician at Brigham and Women’s Hospital, and clinician-scientist with the Precision Vaccines Program at Boston Children’s Hospital in Massachusetts.
Patients should be encouraged to get a bivalent booster in addition to the initial monovalent vaccine series, said Sarah Hochman, MD, assistant professor at NYU Grossman School of Medicine and section chief of infectious diseases at Tisch Hospital in New York, New York.
“As new variants arise, new vaccines likely will be made to better match these variants, and staying up to date with these new boosters will be important,” Dr Hochman said.
Staying up to date on vaccinations is particularly important for hematopoietic stem cell transplant recipients, noted Eric Tam, MD, a blood and marrow transplant and hematology-oncology specialist at the USC Norris Comprehensive Cancer Center at Keck Medicine in Los Angeles, California.
“Post-hematopoietic stem cell transplant patients need to be revaccinated, usually after 3 months post-transplant,” he said.
Additional Protective Measures, Emerging Challenges
Patients should “continue to follow nonpharmacological behavioral preventative measures, including avoiding crowds, masking in public, social distancing, and hand hygiene,” advised Sherif Mossad, MD, an infectious disease specialist at Cleveland Clinic and associate professor in the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University in Ohio.
Dr Mossad also noted the importance of at-home testing using COVID-19 rapid antigen detection tests. Patients should self-test if they develop COVID-19 symptoms, and a positive test should prompt contact with their health care provider. Symptomatic patients who test negative should pursue PCR testing.
Close contacts of cancer patients should follow these measures as well and stay up to date with vaccinations to create a “circle of protection” around patients, Dr Mossad said.
With the newer variants, the “virus binds more strongly to our cells and has mutations that allow it to escape the immune response,” said Jim Boonyaratanakornkit, MD, PhD, an infectious disease specialist and researcher at the Fred Hutchinson Cancer Center in Seattle, Washington. The greater transmissibility of these variants underscores the importance of preventive measures, he added.
“While we don’t have a single ‘magic bullet’ for prevention and protection for our patients, the combination of vaccination, masking, and testing is the best way to optimize protection using all the tools available,” Dr Sherman said.
Unfortunately, these tools are becoming more difficult for cancer patients and the general public to use as the pandemic wears on. Though anecdotal reports suggest cancer patients tend to wear masks and would like others to wear masks around them, mask mandates are largely a thing of the past, even in some health care settings.17-19
Another potential barrier to protecting patients from COVID-19 is the impending end of the public health emergency, which will take place on May 11.20 Although COVID-19 vaccines will remain available and Moderna’s vaccines will remain free, Pfizer is planning to charge for its COVID-19 vaccines.21
The end of the public health emergency also means that patients with Medicare will no longer receive free at-home COVID-19 tests.22 Some patients with private insurance may have access to free at-home tests, but others may not. Likewise, COVID-19 tests ordered or given by health care professionals may or may not be free after the public health emergency ends.
One method of COVID-19 prevention that was found to be effective for cancer patients but is no longer an option is tixagevimab-cilgavimab (Evusheld).23-25 The US Food and Drug Administration (FDA) recently withdrew the emergency use authorization (EUA) for Evusheld when it was shown to be ineffective against more than 90% of the omicron subvariants circulating in the United States at the time.
Changes to COVID-19 Treatment, Remaining Options
Like the case with Evusheld, many mAbs that were previously authorized for COVID-19 treatment are no longer authorized for use because they are not active against currently circulating variants, Dr Hochman said.
Over the course of the pandemic, the FDA has revoked EUAs for several mAbs once used to treat COVID-19, including bamlanivimab-etesevimab, casirivimab-imdevimab (REGEN-COV), bamlanivimab alone, sotrovimab, and bebtelovimab.26-31
However, there are a few antiviral therapies that are expected to remain active against the dominant subvariants of SARS-CoV-2 when administered early in the course of illness. These include nirmatrelvir-ritonavir (Paxlovid), remdesivir, and molnupiravir.32
“Paxlovid is the preferred treatment for most outpatients, or remdesivir if Paxlovid is contraindicated, and the oral antiviral molnupiravir is authorized as an alternative when Paxlovid and remdesivir are not accessible or clinically appropriate,” Dr Tam said.33
Due to the potential for severe drug-drug interactions with Paxlovid, particularly with certain immunosuppressant medications, close monitoring and dose adjustments may be needed when initiating Paxlovid, Dr Tam noted.
“I always confer with a pharmacist first to ensure that Paxlovid won’t have any drug-drug interactions with the medications my patients are already on,” said Rahul Banerjee, MD, an assistant professor in medical oncology at the University of Washington and the Fred Hutchinson Cancer Center in Seattle.
Dr Hochman explained that while molnupiravir does not carry the risk of drug-drug interactions associated with Paxlovid, it does “pose a theoretical risk of being incorporated into host DNA, leading to mutations,” and thus is contraindicated for use in pregnant patients or for “men of reproductive potential who are sexually active with women of childbearing potential for the duration of treatment and for 3 months after completing treatment, unless they use a reliable method of contraception.”34
Dr Mossad also noted that clinicians should be aware of the risk for rebound symptoms in patients treated with Paxlovid or molnupiravir.35,36
For patients who are hospitalized for COVID-19 but don’t require oxygen, remdesivir is recommended.37 For hospitalized patients who require conventional oxygen, options include remdesivir plus dexamethasone, baricitinib, and tocilizumab. Baricitinib and tocilizumab can be combined with dexamethasone in patients who require high-flow nasal cannula oxygen, noninvasive ventilation, mechanical ventilation, or extracorporeal membrane oxygenation.
COVID-19 convalescent plasma, in the outpatient or inpatient setting, is an additional option for patients who have immunosuppressive disease or are receiving immunosuppressive treatment.38
For pediatric cancer patients, treatment strategies are limited, said Diego Hijano, MD, assistant faculty member in the department of infectious diseases at St. Jude Children’s Research Hospital in Memphis, Tennessee.
Paxlovid can be used to treat mild to moderate COVID-19 in nonhospitalized patients who are 12 years or older, weigh at least 40 kg, and are at high risk of progression to severe COVID-19.39
However, for children under 12 years of age who are high risk and have mild-to-moderate COVID-19 symptoms, remdesivir is the only available treatment that can be used to prevent severe disease, Dr Hijano said.
For children who already have severe COVID-19, remdesivir, dexamethasone, baracitinib, tofacitinib, and tocalizumab are options.40
“For patients who have moderate to severe disease requiring hospitalization and supplemental oxygen, we use remdesivir and dexamethasone,” Dr Hijano noted. “For patients who can’t receive steroids or have a lack of response in the first 24 hours, we consider the use of baricitinib.”
Unmet Needs: Better Vaccines, Treatments, and Guidelines
There are still many areas of need in COVID-19 prevention and treatment, according to experts.
“The biggest needs are in vaccine research, drug development, and education targeting vaccine hesitancy,” Dr Hochman said. Researchers should aim to “develop vaccines that target areas other than the SARS-CoV-2 spike protein, which has mutated over time and resulted in reduced protection from prior SARS-CoV-2 infection,” she added.
Dr Banerjee pointed to the need to develop mAbs like Evusheld that could protect against new variants and to create a faster pipeline to get these mAbs to vulnerable patients.
“Many of our patients aren’t able to mount adequate responses to COVID-19 vaccines because of their underlying malignancies or the treatments they’re on, so the ability to confer passive immunity is critical,” he said.
Dr Hijano hopes to see changes in the regulatory process to allow the identification of a prophylactic mAb for younger children.
“The fast pace at which SARS-CoV-2 changes has left children under 12 years to almost never have a monoclonal option available, because every time companies were opening trials in children, the monoclonals were ineffective against the newest variants and the study could not continue,” he explained. He also noted the need for antivirals that can be used in all age groups.
Another unmet need is COVID-19 management guidelines relevant to specific patient groups.
“Most of the current guidelines are for immunocompromised patients in general, which lumps together people with hematologic malignancies, solid organ transplantation, and those receiving immunomodulatory therapy for inflammatory or rheumatologic conditions,” Dr Sherman said. “We urgently need more specific guidelines for each of these groups of patients, since the underlying disease and treatments received impact the immune system differently.”
“Clinicians need to be able to provide evidence-based recommendations to protect all patients with cancer and be able to address the vast amount of misinformation propagated on social media and through other avenues,” Dr Gralow said. “That means staying up to date and understanding the evidence and rationale for recommendations.”
Disclosures: Dr Mossad, Dr Gralow, Dr Hochman, Dr Tam, and Dr Hijano reported having no relevant disclosures. Dr Banerjee disclosed relationships with SparkCures, Sanofi Pasteur, Genentech/Roche, Janssen Oncology, Bristol-Myers Squibb/Celgene, and Pack Health. Dr Sherman is involved in COVID-19, HIV, and other vaccine trials conducted in collaboration with the National Institutes of Health, HIV Vaccine Trials Network, COVID Vaccine Prevention Network. Dr Boonyaratanakornkit disclosed research funding from Vir Biotechnology and GlaxoSmithKline.
1. Patel P, Twentyman E, Koumans E, et al. Information for persons who are immunocompromised regarding prevention and treatment of SARS-CoV-2 infection in the context of currently circulating omicron sublineages — United States, January 2023. MMWR Morb Mortal Wkly Rep. 2023;72(5):128–131. doi:10.15585.mmwr.mm7205e3
2. Forster V. Responses to COVID-19 vaccines vary in patients with hematologic malignancies. Cancer Therapy Advisor. Published August 20, 2021. Accessed February 28, 2023.
3. Storrs C. Responses to COVID-19 vaccines in cancer patients: Impact of tumor and treatment type. Cancer Therapy Advisor. Published August 31, 2021. Accessed February 28, 2023.
4. Storrs C. Cancer patients may have double the risk of breakthrough infection after COVID-19 vaccination. Cancer Therapy Advisor. Published December 7, 2021. Accessed February 28, 2023.
5. Goodman J. Risk of death from COVID-19 “remains high” in vaccinated cancer patients. Cancer Therapy Advisor. Published February 16, 2022. Accessed February 28, 2023.
6. Schieszer J. Risk of breakthrough COVID-19 higher for patients with cancer. Cancer Therapy Advisor. Published April 7, 2022. Accessed February 28, 2023.
7. Schieszer J. Breakthrough COVID-19 in cancer patients more common during omicron wave. Cancer Therapy Advisor. Published April 21, 2022. Accessed February 28, 2023.
8. Blevins Primeau AS. Cancer patients have higher risk of breakthrough COVID-19, poor outcomes. Cancer Therapy Advisor. Published January 9, 2023. Accessed February 28, 2023.
9. Link-Gelles R, Ciesla AA, Fleming-Dutra KE, et al. Effectiveness of bivalent mRNA vaccines in preventing symptomatic SARS-CoV-2 infection — Increasing community access to testing program, United States, September–November 2022. MMWR Morb Mortal Wkly Rep. 2022;71(48):1526–1530. doi:10.15585/mmwr.mm7148e1
10. Link-Gelles R, Ciesla AA, Roper LE, et al. Early estimates of bivalent mRNA booster dose vaccine effectiveness in preventing symptomatic SARS-CoV-2 infection attributable to omicron BA.5- and XBB/XBB.1.5-related sublineages among immunocompetent adults – Increasing community access to testing program, United States, December 2022-January 2023. MMWR Morb Mortal Wkly Rep. 2023;72(5):119-124. doi:10.15585/mmwr.mm7205e1
11. Lin D-Y, Xu Y, Gu Y, et al. Effectiveness of bivalent boosters against severe omicron infection. N Engl J Med. 2023; 388:764-766. doi:10.1056/NEJMc2215471
12. Chalkias S, Harper C, Vrbicky K, et al. A bivalent omicron-containing booster vaccine against Covid-19. N Engl J Med. 2022 Oct 6;387(14):1279-1291. doi:10.1056/NEJMoa2208343
13. Wang, Q, Bowen A, Valdez R, et al. Antibody response to omicron BA.4–BA.5 bivalent booster. N Engl J Med. 2023; 388:567-569. doi:10.1056/NEJMc2213907
14. Miller J, Hachmann NP, Collier AY, et al. Substantial neutralization escape by sars-cov-2 omicron variants BQ.1.1 and XBB.1. N Engl J Med. 2023; 388:662-664. doi:10.1056/NEJMc2214314
15. Collier AY, Miller J, Hachmann NP, et al. Immunogenicity of BA.5 bivalent mRNA vaccine boosters. N Engl J Med. 2023;388:565-567. doi:10.1056/NEJMc2213948
16. Healy LM. Bivalent COVID-19 vaccine may not protect cancer patients from current variants. Cancer Therapy Advisor. Published February 15, 2023. Accessed February 28, 2023.
17. Forster V. Lack of mask mandates leaves cancer patients feeling unprotected. Cancer Therapy Advisor. Published July 6, 2022. Accessed February 28, 2023.
18. Lee BY. New York state drops face mask requirements for hospitals, health care facilities. Forbes. Published February 12, 2023. Accessed February 28, 2023.
19. Markowitz A. State-by-state guide to face mask requirements. AARP. Updated February 13, 2023. Accessed February 28, 2023.
20. Biden to lift COVID-19 emergency measures in May. HealthDay via Cancer Therapy Advisor. Published February 2, 2023. Accessed February 28, 2023.
21. Moderna will not be charging for COVID-19 vaccination after public health emergency ends. HealthDay via Cancer Therapy Advisor. Published February 21, 2023. Accessed February 28, 2023.
22. Cox C, Kates J, Cubanski J, Tolbert J. The end of the COVID-19 public health emergency: Details on health coverage and access. Kaiser Family Foundation. Published Feb 03, 2023. Accessed February 28, 2023.
23. Lawrence L. COVID-19 vaccine booster, Evusheld improve protection for patients with blood cancers. Cancer Therapy Advisor. Published July 13, 2022. Accessed February 28, 2023.
24. Goodman J. Evusheld appears less effective against omicron for patients with blood cancer. Cancer Therapy Advisor. Published May 31, 2022. Accessed February 28, 2023.
25. FDA announces Evusheld is not currently authorized for emergency use in the U.S. US Food and Drug Administration. Updated January 26, 2023. Accessed February 28, 2023.
26. Coronavirus (COVID-19) update: FDA revokes emergency use authorization for monoclonal antibody bamlanivimab. US Food and Drug Administration. Published April 16, 2021. Accessed February 28, 2023.
27. Coronavirus (COVID-19) update: FDA limits use of certain monoclonal antibodies to treat COVID-19 due to the omicron variant. US Food and Drug Administration. Published January 24, 2022. Accessed February 28, 2023.
28. REGEN-COV usage revisions. Regeneron. Published January 24, 2022. Accessed February 28, 2023.
29. Emergency use authorization (EUA) for the treatment or post-exposure prophylaxis of COVID-19. Lilly. Accessed February 28, 2023.
30. FDA updates sotrovimab emergency use authorization. US Food and Drug Administration. Updated April 5, 2022. Accessed February 28, 2023.
31. FDA announces bebtelovimab is not currently authorized in any US region. US Food and Drug Administration. Updated November 30, 2022. Accessed February 28, 2023.
32. Interim clinical considerations for COVID-19 treatment in outpatients. Centers for Disease Control and Prevention. Updated February 10, 2023. Accessed February 28, 2023.
33. Therapeutic management of nonhospitalized adults with COVID-19. National Institutes of Health. Updated December 28, 2022. Accessed February 28, 2023.
34. Waters MD, Warren S, Hughes C, Lewis P, Zhang F. Human genetic risk of treatment with antiviral nucleoside analog drugs that induce lethal mutagenesis: The special case of molnupiravir. Environ Mol Mutagen. 2022;63(1):37-63. doi:10.1002/em.22471
35. Wang L, Berger NA, Davis PB, Kaelber DC, Volkow ND, Xu R. COVID-19 rebound after Paxlovid and molnupiravir during January-June 2022. medRxiv [Preprint]. 2022:2022.06.21.22276724. doi:10.1101/2022.06.21.22276724
36. Wong GL, Yip TC, Lai MS, Wong VW, Hui DS, Lui GC. Incidence of viral rebound after treatment with nirmatrelvir-ritonavir and molnupiravir. JAMA Netw Open. 2022;5(12):e2245086. doi:10.1001/jamanetworkopen.2022.45086
37. Therapeutic management of hospitalized adults with COVID-19. National Institutes of Health. Updated August 8, 2022. Accessed February 28, 2023.
38. COVID-19 convalescent plasma. COVID-19 treatment guidelines. National Institutes of Health. Updated December 1, 2022. Accessed February 28, 2023.
39. Therapeutic management of nonhospitalized children with COVID-19. COVID-19 treatment guidelines. National Institutes of Health. Updated December 28, 2022. Accessed February 28, 2023.
40. Therapeutic management of hospitalized children with COVID-19. COVID-19 treatment guidelines. National Institutes of Health. Updated August 8, 2022. Accessed February 28, 2023.
This article originally appeared on Cancer Therapy Advisor