Coming down with a bug is never fun, but for patients receiving cellular therapies such as hematopoietic cell transplant (HCT) or chimeric antigen receptor T cell (CAR-T), getting an infection is one of the last things they want. This is especially important for these patients because they are put into a fragile immune state where they are highly susceptible to infectious diseases due to immune depletion from the pre-therapy conditioning radiation or chemotherapies. The cellular transplant itself also leaves them in a compromised condition since it can result in strong inflammatory responses as the new cells settle in (and hopefully successfully engraft). During the COVID-19 pandemic, patients who’d received either HCT or CAR-T were at higher risk than the average public for severe outcomes if they contracted the virus after their cellular transplant, but whether there was also increased risk if they became infected before the transplant wasn’t well documented. Despite not having a clear understanding of the consequences of SARS-CoV-2 infection prior to cellular therapy, current guidelines recommend delaying transplantation, stemming from data of outcomes from other respiratory infections in these patients. While this could be a reasonable approach to err on the side of caution, it also can result in requiring additional or delayed pre-transplant chemotherapy and in more concerning cases, disease progression.
Recently, Internal Medical Resident Dr. Ila Nimgaonkar in Dr. Joshua Hill’s lab published in Clinical Infectious Diseases their findings that, in fact, SARS-CoV-2 infection just prior to either HCT or CAR-T therapy was not associated with poor outcomes after transplant, regardless of whether there was a delay in treatment. With the Hutch being a pre-eminent center for cellular therapies, the authors were able to acquire data on 37 patients who tested positive for SARS-CoV-2 within 90 days before scheduled cellular therapies between January 2020 and November 2022. While this number may not sound very high, Dr. Nimgaonkar remarked that it was “actually a large sample size” considering that most other publications at the time were either case studies or had much smaller samples of patients. During the time frame that their study sampled, Fred Hutch performed weekly SARS-CoV-2 testing on all of their patients. But if a patient tested positive, especially if they were asymptomatic, Dr. Nimgaonkar added that with conflicting or unclear guidelines, “what do you do with that?” Since these patients are some of the most immunocompromised individuals out there, there is clearly a need to define appropriate measures to ensure their well-being throughout treatment.
When looking at their sample of 37 patients, all but one patient had tested negative for SARS-CoV-2 by the time of transplant and remained negative in the 100 days post-therapy. Most patients were asymptomatic or had mild COVID-19 symptoms, with a few having visible ground-glass opacities by chest radiographic imaging, something that is often seen in viral pneumonia, and two patients were hospitalized while they tested positive. However, regardless of variable disease severities or clinical manifestations prior to cellular therapy, none of the patients had worsening conditions afterwards, an important and slightly surprising finding for the research team. Since the current guidelines recommend delaying cellular therapy if the patient tests positive for SARS-CoV-2, the research team wanted to see if any delay might be associated with more beneficial outcomes after cellular therapy. They observed that the majority of patients (70%) had some form of delay due to their SARS-CoV-2 infection. As a result of this, some patients had to repeat or delay pre-transplant workups, had delays in apheresis, or in pre-transplant chemotherapy. A few patients required additional chemotherapy, and for one patient, their underlying multiple myeloma progressed rapidly during their delay. Some patients saw no delay, mainly those receiving allogeneic HCT, and compared to those who were delayed, the research team did not observe any worse outcomes after therapy. This was particularly important to them, as it highlighted that delay would not be necessary for these patients but may actually cause additional hardship due to risks associated with delaying therapy.
Overall, the results from this retrospective study provide an important piece of data for patients receiving cellular therapies for blood-related malignancies. As the pandemic has receded, Fred Hutch no longer performs weekly COVID-19 screenings, and Dr. Nimgaonkar pointed out that this is at least supported by their data, highlighting that a positive test prior to therapy would not put them at higher risk for complications. She also noted that their study could have had limitations if their sampled population excluded individuals whose cellular therapy did not end up happening. If this was the case, they would not be able to define if a particularly serious SARS-CoV-2 infection was to blame. However, for patients with moderate, mild, or asymptomatic COVID-19 before they undergo cellular therapy, there is no strong reason to believe that this should cause alarm or any delay in treatment. Dr. Nimgaonkar hopes that this large-scale study can “help hone the guidelines” on how to approach this situation, and to give patients the best chance to return to a normal life.
Nimgaonkar I, Yoke LH, Roychoudhury P, Flaherty PW, Oshima MU, Weixler A, Gauthier J, Greninger AL, Mielcarek M, Boeckh M, Liu C, Hill JA. Outcomes in Hematopoietic Cell Transplant and Chimeric Antigen Receptor T Cell Therapy Recipients with Pre-Cellular Therapy SARS-CoV-2 Infection. Clin Infect Dis. 2024 Mar 1:ciae116. doi: 10.1093/cid/ciae116. Epub ahead of print. PMID: 38427848.
Ila Nimgaonkar was supported by the Physician Scientist Learning Pathway through the University of Washington Internal Medicine Residency Program for this Spotlight work.
Fred Hutch/University of Washington/Seattle Children's Cancer Consortium members Drs. Masumi Ueda Oshima, Jordan Gauthier, Marco Mielcarek, Michael Boeckh, Catherine Liu, and Joshua Hill contributed to this work.