Perales Examines the Impact of COVID-19 on Recipients of Cellular Therapies for Cancer

Miguel-Angel Perales, MD

Following stem cell transplant or treatment with CAR T-cell therapies, patients with hematologic malignancies and coronavirus disease 2019 (COVID-19) tend to have favorable outcomes, especially if they are diagnosed in complete remission (CR) and further out from their cell infusion, according to Miguel-Angel Perales, MD, underscoring that care should not be delayed despite the ongoing pandemic.

“Delayed therapy results in patients with relapse or progression of disease who did not receive the intended cellular therapy; [we’ve seen this happen] in 34% of cases,” Perales, chief of the Adult Bone Marrow Transplant Service at Memorial Sloan Kettering Cancer Center (MSKCC), said during a presentation delivered at the 2021 AACR Virtual Meeting on COVID-19 and Cancer.¹ “Given that we can avoid the risk of nosocomial transmission, I think this clearly indicates that we should be careful about how we manage these patients and not try to delay their care.”

In his talk, Perales highlighted registry data detailing the impact of the pandemic on cellular treatment in patients with cancer, outcomes of patients who were infected with the virus and received hematopoietic cell transplantation, and the impact of virus-related delays in care.

Examining Registry Data to Gain Insight on Outcomes

Data reported to the ASH Research Collaborative COVID-19 Registry for Hematology, a global reference tool available to the public, showed that as of January 15, 2021, a total of 813 malignant and non-malignant cases of COVID-19 were reported, with just over 500 cases reported in the United States alone.²

When looking at cellular therapies received prior to a diagnosis with the virus, 10 patients had received CAR T-cell therapies (6 recovered, 4 died), 46 patients had undergone allogeneic stem cell transplantation (34 recovered, 7 died, 5 had unknown outcome), and the majority, or 78 patients, had undergone autologous stem cell transplantation (67 recovered, 7 died, 4 had unknown outcome).

An earlier analysis of data collected from this registry showed that among the first 250 patients for whom data were collected, the overall mortality rate was 28% (95% CI, 23%-34%).³ However, in patients with moderate to severe COVID-19 infection, the mortality rate was even higher, at 42% (95% CI, 34%-50%). “This is a condition that has significantly impacted our patients with hematologic malignancies,” noted Perales.

Another registry, of the Center for International Blood & Marrow Transplant Research (CIBMTR), requires the inclusion of outcomes of patients who have undergone transplantation or received CAR T cells.⁴ As of January 15, 2021, data for 1258 patients from 195 centers were reported to the registry and showed that 50.08% of patients had undergone allogeneic transplantation and 44.66% had undergone autologous transplantation. Only a small percentage of patients received cell therapy, according to Perales.

The age of patients at the time of infection ranged from less than 20 years to older than 70 years, with the majority of patients between the ages of 60 years and 69 years. When looking at infections by region, 29.35% of cases were reported in the Midwest, 23.44% were reported in the Northeast, and 22.73% were reported in the South. The majority of cases occurred within the first 2 years of their infusion. A total of 614 cases—almost half of all patients—had their infection resolve, while 58 experienced improvement; 187 patients had died.

In a subsequent paper, investigators examined risk factors associated with death from COVID-19 in recipients of allogeneic transplantation based on data from the CIBTR registry.⁵ Results from the multivariate analysis showed that age greater than 50 years (P = .016), male gender (P = .006), and COVID-19 infection in less than 12 months following transplantation (P = .019) were all significantly associated with increased risk of death.

“Interestingly, race and ethnicity were not significant in this series,” noted Perales. “Similarly, when we look at patients [who have undergone] autologous transplant, the only factor that we saw was the diagnosis of lymphoma versus myeloma. Other factors were not significant.”

Lessons Learned at MSKCC

In another analysis, investigators examined outcomes of patients following transplant who were infected with the virus at MSKCC. Of the first 77 patients diagnosed between March 15, 2020 and May 7, 2020, 37 had undergone autologous transplant, 35 had undergone allogeneic transplant, and 5 had received CAR T-cell therapy.⁶

The disease distribution was as expected, according to Perales. Thirty-eight percent of patients had plasma cell disease, 23% had acute leukemia, 23% had aggressive non-Hodgkin lymphoma (NHL), 5% had Hodgkin lymphoma, 4% had chronic myeloid leukemia, 4% had myelodysplastic syndrome, and 3% had indolent NHL.

“When you look at day [of infection] post infusion, you see there was a significant range,” said Perales. “In fact, the number of patients were diagnosed with COVID-19 several months or even years after their cell therapy. These are the demographics of 77 patients, but this is representative of the patients that we transplant at our center.”

Notably, 44% of patients did not have any comorbidities. Investigators also examined the home medications that patients were receiving at the time of their COVID-19 diagnosis. Here, 10 patients were receiving steroids, 18 were receiving immunomodulatory agents, 4 were receiving anticoagulation agents, and 14 were receiving immunosuppressive drugs.

Almost half, or 48%, of patients had mild COVID-19 infection, so they were not admitted to the hospital. Twenty-six percent of patients had moderate infection, and thus, were admitted to the hospital, while 22% had severe infection and were either admitted to the intensive care unit or died.

“In that group, the majority of them actually had active malignancy, unlike the other 2 groups where the majority actually were in remission,” said Perales. “Patients who required high levels of oxygen [were often those who] had active malignancy.”

Results from a univariate analysis looking at the predictors of disease severity revealed significant associations between the presence of comorbidities and infiltrates on imaging at the time of diagnosis. “Overall, however, we were able to see favorable outcomes with patients after COVID-19 infection,” said Perales. “Two-thirds of patients actually had a resolution. We did see 14 deaths, which represented 18% of patients. This was 41% of patients who were admitted, but particularly those with an active malignancy.”

Among patients who were admitted to the hospital but had a malignancy that was in remission, the mortality rate was 21%. “This was due, in part, to the fact that in many cases, patients or their family members decided to forego aggressive medical care.”

Additional data revealed that COVID-19 was linked with a drop in lymphocyte populations across the board, added Perales. Notably, lymphopenia with COVID-19 was not found to impair long-term immune reconstitution in patients who had undergone bone marrow transplant.

When looking at survival in patients after infection with COVID-19, overall outcomes were found to be favorable.

Risk of Nosocomial Infection

Investigators also examined the risk of nosocomial infections in patients who had undergone transplantation or received cellular treatment in light of the pandemic. They looked at a series of 44 cases.

In March 2020, 2 healthcare workers were exposed at MSKCC and 3 patients had documented COVID-19 infection. One patient was receiving treatment in the inpatient setting, but the patient did have frequent visits from family members, according to Perales. “So, it’s unclear when or how the exposure occurred,” Perales said. The patient ended up dying.

Two additional patients may have been exposed in the donor room while they were collecting the stem cell from the autologous transplant, added Perales. One patient eventually died from the virus.

“Again, it’s unclear whether these patients were infected in the center or in the community, as COVID-19 was very prevalent at the time,” said Perales. “Importantly, we have not seen any additional cases of potential or definite COVID-19 nosocomial infection since March 2020 at our center.”

Impact of COVID-19 on Treatment Delays

When examining the impact of the pandemic on treatment delays, in March 2020, investigators started to prospectively collect data from patients whose transplant or cellular therapy was delayed as a result of the impact of the virus on resources at the hospital, particularly the capability of using intensive care unit beds.¹

Results showed that 85 patients delayed treatment; of those patients, 29 have not received their intended cellular treatment. Sixteen were supposed to receive autologous transplant, 12 were supposed to undergo allogeneic transplant, and 1 was supposed to receive CAR T-cell therapy.

Of the 56 patients who eventually proceeded to treatment, 62% received autologous transplant, 67% received allogeneic transplant, and 86% received CAR T-cell therapy. The biggest reason for not proceeding to treatment with autologous transplant and CAR T-cell therapy was because they were deferred due to good disease control. Other reasons included was because of a new comorbidity (12%) or they died from the virus. The most prominent reason for not proceeding to allogeneic transplant during the pandemic was progression of disease (42%).

“We conclude that patients who are recipients of allogeneic transplant, and particularly those with acute leukemia, as much as possible should proceed to their indicated therapy and not be delayed,” concluded Perales.

References

1. Perales M-A. Impact of COVID-19 on recipients of cellular therapies. Presented at: 2021 AACR Virtual Meeting on COVID-19 and Cancer; February 3-5, 2021; Virtual.
2. ASH RC COVID-19 Registry for Hematology. ASH Research Collaborative. Accessed February 5, 2021. http://bit.ly/3huP7CG.
3. Wood WA, Neuberg DS, Thompson JC, et al. Outcomes of patients with hematologic malignancies and COVID-19: a report from the ASH Research Collaborative Data Hub. Blood. 2020;4(23):5966-5975. doi:10.1182/bloodadvances.2020003170
4. COVID-19 updates. Center for International Blood & Marrow Transplant Research. Accessed February 5, 2021. http://bit.ly/39V0e6W.
5. Sharma A, Bhatt NS, St Martin A, et al. Clinical characteristics and outcomes of COVID-19 in haematopoietic stem-cell transplantation recipients: an observational cohort study. Lancet Hamatol. Published online January 19, 2021. doi:10.1016/S2352-3026(20)30429-4
6. Shah GL, DeWolf S, Lee YL, et al. Favorable outcomes of COVID-19 recipients of hematopoietic cell transplantation. J Clin Invest. Published online December 1, 2020. doi:10.1172/JCI141777