Experts discuss management of cancer therapies in the era of COVID-19
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Management of cancer therapies in the era of COVID-19 infection and vaccination requires careful consideration of both disease and patient characteristics, according to members of a crossfire panel at Chemotherapy Foundation Symposium.
Panelists included Ajai Chari, MD, professor of medicine, hematology and medical oncology at Icahn School of Medicine at Mount Sinai; Pinkal Desai, MD, MPH, assistant professor of medicine at Weill Cornell Medicine; Peter Martin, MD, associate professor of medicine and chief of the lymphoma program at Weill Cornell Medicine; and Jacqueline C. Barrientos, MD, associate professor in the division of hematology and medical oncology at Donald and Barbara Zucker School of Medicine at Hofstra/Northwell.
Q: What are the risk factors for worse COVID-19 outcomes in patients with cancer?
Chari: Results of a global data set have shown that age, renal failure, uncontrolled myeloma and high-risk myeloma are associated with worse outcomes. However, no specific treatments appeared associated with worse outcomes in patients with COVID-19. There are no data that suggest withholding treatments — including transplant or CAR T-cell therapy. We can adjust oral therapy in older, fragile patients whose disease is well-controlled, whereas in younger, fit patients we need to continue treatment aggressively because uncontrolled myeloma and renal failure would compromise the patient.
Desai: For patients with acute myeloid leukemia and myelodysplastic syndrome [MDS], we have paradoxically found that physicians’ ability to prognosticate the disease is what leads to higher mortality. If a prognosis for primary AML is less than 6 months, it is associated with higher mortality. However, remission status or active disease does not appear associated with mortality. Regarding therapy, chemotherapy is extremely aggressive, and we would not stop therapy in a patient with or without COVID-19. Vaccination status also does not matter, but these individuals should get vaccinated. In the past, when we have withheld therapy due to COVID-19, it did not help, so we should continue to treat leukemia and MDS aggressively in patients with COVID-19.
Martin: Patients with blood cancers in general appear to fare worse from COVID-19 compared with patients with solid tumors. This appears most so in patients with B-cell malignancies, and we are learning that this is from B-cell-depleting treatments. These treatments appear associated with an increased risk for mortality and morbidity following infection, as well as a poor response to vaccination.
Barrientos: For patients with hairy cell leukemia, we alter treatment depending on peak and nonpeak COVID-19 season. For CLL [chronic lymphoblastic leukemia], we have moved away from chemotherapy; however, patients on certain therapies may experience issues with development of antibodies. As such, the moment these patients are exposed to COVID-19, we do not wait for a positive COVID-19 test. We immediately start them on monoclonal antibodies, which are lifesaving in these patients. This is one of the interventions that we actively do at our institution. Monoclonal antibodies must be administered as soon as possible in these patients.
Q: Do certain cancer types and treatments affect COVID-19 vaccine response?
Desai: For patients with AML and MDS, we are not seeing issues with vaccine response. We try to not vaccinate a patient who is actively ablated and in the middle of consolidation therapy, as there are practically no cells. On count recovery, we try to create the vaccination schedule in a way that as the counts recover, vaccinations happen. Right now, we recommend a booster dose even though we do not know the longevity of response yet for patients with AML and MDS. For patients with ALL, therapies are associated with toxicity and tend to last for years. We have seen subpar COVID-19 vaccine responses in patients with [acute lymphoblastic leukemia] compared with those with AML and MDS, for whom we recommend vaccination and booster doses.
Martin: In patients with lymphoma, it is complicated because there are so many types of lymphomas. Many but not all patients with Hodgkin lymphoma or T-cell lymphoma respond to the COVID-19 vaccines. This will ultimately require a meta-analysis a year or so from now to try to tease out which factors may or may not be associated with vaccine response in those patients.
Barrientos: Patients with CLL unfortunately have poor T-cell function, and this is why CAR T-cell therapy does not work as well in these patients as it does for other patients with lymphoma. As such, it is difficult for these patients to achieve a response from COVID-19 vaccination. Regarding BTK [Bruton tyrosine kinase] inhibitors for CLL, there are no prospective data yet. The NIH has a current ongoing trial where they are stopping BTK inhibitors a couple of days before and a couple of days after COVID-19 vaccination to see if that may boost the percentage of patients who respond to the vaccine. We already know from data from hepatitis B vaccination that it blunted the antibody response in patients with CLL. Therefore, at this moment, we advise patients with CLL to continue treatment with BTK inhibitors, get vaccinated and, if they do not produce antibodies, get a booster unless they experience major toxicity. Even if chances are low to develop antibodies, at least a little bit is better than zero.
Chari: For patients with multiple myeloma, vaccine response is interesting. These patients have higher mortality rates than age-matched controls and, as a group, have a lower serologic vaccination response than age-matched controls. Interestingly, patients with myeloma who have had COVID-19 have antibody responses identical to age-matched controls. There is something about patients who have had the infection that seems to be quite immunogenic. With respect to therapies in our data set and other data sets including about 250 patients with myeloma, those who lack serologic response also lack T-cell response, so there seems to be something similar going on there. Data have shown that of all treatment classes, 15% of patients with myeloma do not achieve a serologic response — half of which are anti-CD38 monoclonal antibodies, and others targeted B-cell maturation antigen. Bottom line, I tell my patients to get a third vaccine dose, not the booster. We want these patients to get the third full dose of the [messenger RNA] vaccine, not the dose-attenuation, because of the impact to these patients.
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Chari A, et al. Medical Crossfire: Managing chemotherapy in the era of COVID-19 disease and vaccinations. Presented at: 39th Annual Chemotherapy Foundation Symposium: Innovative Cancer Therapy for Tomorrow; Nov. 3-5, 2021.
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