Worse outcomes for immunosuppressed patients with cancer and COVID-19 treated with immunotherapy
A report published in JAMA Oncology suggests that cancer patients with baseline immunosuppression and COVID-19 experience worse outcomes and an increased incidence of cytokine storm when treated with systemic anticancer therapy, and particularly immunotherapy.1 Meanwhile patients without immunosuppression can safely receive anticancer regimens.1
COVID-19 disproportionately affects cancer patients with high rates of hospitalization and death,2 some of which have been linked to immunosuppressive anticancer treatment such as cytotoxic chemotherapy.3 However, the true impact of immunotherapies and immunosuppressive treatment on outcomes of patients with cancer and COVID-19 has yet to be established, with studies so far presenting conflicting results.4-6
Several studies have been established to explore whether immune checkpoint inhibitors (ICIs) could overcome the immunosuppression associated with COVID-19 by reversing CD8+ T-cell exhaustion and improve outcomes (NCT04413838, NCT04268537, NCT04356508). Yet there has been concern that ICIs may also impact negatively on COVID-19 outcomes, with the induction of immune activation, either through direct cytotoxicity or cytokine release, potentially exacerbating the inflammation which is characteristic of COVID-19.7-9 Meanwhile immunosuppression, which Chris Labaki, MD, of the Dana-Farber Cancer Institute, Boston, MA, notes is common for cancer patients, may limit antiviral responses and consequently lead to poor outcomes.
The registry-based retrospective cohort study (NCT04354701) included 12,046 patients reported to the COVID-19 and Cancer Consortium (CCC19) registry from March 2020 to May 2022, and sought to evaluate the interplay between immunotherapy, immunosuppression and the outcomes of patients with cancer during COVID-19 infection.1 The primary outcome was COVID-19 severity and the secondary outcome was occurrence of cytokine storm, a state of systemic inflammation resulting in end organ damage. 1
Within the cohort 53.0% of patients were women, 55% were non-Hispanic White, the median (interquartile range [IQR]) age was 65 (54-74) years, and the median (IQR) follow-up was 90 (30-180) days.1
Within the three months prior to COVID-19 diagnosis, 599 (5.0%) patients received IO, 4327 (35.9%) received non-IO systemic anticancer therapies, and 7120 (59.1%) were untreated. In the IO group, 138 (23%) patients died, compared with 856 (20%) in the non-IO group, and 1124 (16%) in the untreated group.1 The raw incidence of cytokine storm was comparable across all groups at 12% (684, 533, and 860 instances for the IO, non-IO, and untreated groups, respectively).1 There was also no difference found in the severity of COVID-19 across the groups in the general population (multivariable adjusted odds ratio [aOR] versus untreated [95% CI] non-IO = 1.01 [0.91-1.12], IO = 0.80 [0.56-1.13]).1
However, in multivariable regression analysis Dr Labaki explained that “immunotherapy was associated with worse outcomes in the immunosuppressed patients with COVID-19, as opposed to the non-immunosuppressed population, with a much higher rate of severe outcomes.” When multivariable analysis was stratified by baseline immunosuppression both the IO and non-IO groups were associated with worse COVID-19 outcomes when there was pre-existing immunosuppression, compared to the untreated group (aOR [95% CI], 3.33 [1.38-8.01], and 1.79 [1.36-2.35], respectively).1
“In regards to the secondary endpoint of cytokine storm, we also saw very similar results,” stated Dr Labaki. A higher risk of cytokine storm with IO and non-IO versus untreated was identified among immunosuppressed patients (aOR [95% CI], 4.41 [1.71-11.38], and 2.32 [1.42-3.79], respectively).1
“In general, there is an association with immunotherapy and worse outcomes, specifically in patients who present a state of baseline immunosuppression after confounding for all clinical and demographic parameters that are relevant to this analysis. This is seen to a lesser extent with non-immunotherapy regimens,” states Dr Labaki. However in his conclusion he notes the importance of not stopping potentially life-saving systemic therapies, even with the association, highlighting the need for immunosuppressed patients to follow stringent regulations with regards to preventative measures for COVID-19.
Written by Hannah Balfour
Edited by Sol Yohannes
- Bakouny Z, Labaki C, Grover P, et al. Interplay of immunosuppression and immunotherapy among patients with cancer and COVID-19. JAMA Oncology. 2022Nov3.
- Bakouny Z, Hawley JE, Choueiri TK, et al. Covid-19 and cancer: Current challenges and perspectives. Cancer Cell. 2020Nov9;38(5):629–46.
- Lee LYW, Cazier J-B, Angelis V, et al. Covid-19 mortality in patients with cancer on chemotherapy or other anticancer treatments: A prospective cohort study. The Lancet. 2020Jun20;395(10241):1919–26.
- Dai M, Liu D, Liu M, et al. Patients with cancer appear more vulnerable to SARS-COV-2: A Multicenter study during the COVID-19 Outbreak. Cancer Discovery. 2020Jun10;10(6):783–91.
- Tian J, Yuan X, Xiao J, et al. Clinical characteristics and risk factors associated with COVID-19 disease severity in patients with cancer in Wuhan, China: A Multicentre, retrospective, cohort study. The Lancet Oncology. 2020Jul21;21(7):893–903.
- Robilotti EV, Babady NE, Mead PA, et al. Determinants of covid-19 disease severity in patients with cancer. Nature Medicine. 2020Aug26;26(8):1218–23.
- Garassino MC, Ribas A. At the crossroads: Covid-19 and immune-checkpoint blockade for cancer. Cancer Immunology Research. 2021Jan15;9(3):261–4.
- Luo J, Rizvi H, Egger JV, et al. Impact of PD-1 blockade on severity of COVID-19 in patients with lung cancers. Cancer Discovery. 2020Aug10;10(8):1121–8.
- Rogiers A, Pires da Silva I, Tentori C, et al. Clinical impact of COVID-19 on patients with cancer treated with immune checkpoint inhibition. Journal for ImmunoTherapy of Cancer. 2021Jan19;9(1).