Oral antivirals for COVID-19 among patients with cancer.

PURPOSE: Immunocompromised individuals, such as those diagnosed with cancer, are at a significantly higher risk for severe illness and mortality when infected with SARS-CoV-2 (COVID-19) than the general population. Two oral antiviral treatments are approved for COVID-19: Paxlovid® (nirmatrelvir/ritonavir) and Lagevrio® (molnupiravir). There is a paucity of data regarding the benefit from these antivirals among immunocompromised patients with cancer, and recent studies have questioned their efficacy among vaccinated patients, even those with risk factors for severe COVID-19. METHODS: We evaluated the efficacy and safety of nirmatrelvir/ritonavir and molnupiravir in preventing severe illness and death using our database of 457 patients with cancer and COVID-19 from Brown University-affiliated hospitals. RESULTS: Sixty-seven patients received nirmatrelvir/ritonavir or molnupiravir and were compared to 45 concurrent controls who received no antiviral treatment despite being eligible to receive it. Administration of nirmatrelvir/ritonavir or molnupiravir was associated with improved survival and lower 90-day all-cause and COVID-19-attributed mortality (p < 0.05) and with lower peak O2 requirements (ordinal odds ratio [OR] 1.52, 95% confidence interval [CI] 0.92-2.56). CONCLUSION: Acknowledging the small size of our sample as a limitation, we concluded that early antiviral treatment might be beneficial to immunocompromised individuals, particularly those with cancer, when infected with SARS-CoV-2. Larger-scale, well-stratified studies are needed in this patient population.

The impact of cancer metastases on COVID-19 outcomes: A COVID-19 and Cancer Consortium registry-based retrospective cohort study.

BACKGROUND: COVID-19 can have a particularly detrimental effect on patients with cancer, but no studies to date have examined if the presence, or site, of metastatic cancer is related to COVID-19 outcomes. METHODS: Using the COVID-19 and Cancer Consortium (CCC19) registry, the authors identified 10,065 patients with COVID-19 and cancer (2325 with and 7740 without metastasis at the time of COVID-19 diagnosis). The primary ordinal outcome was COVID-19 severity: not hospitalized, hospitalized but did not receive supplemental O2, hospitalized and received supplemental O2, admitted to an intensive care unit, received mechanical ventilation, or died from any cause. The authors used ordinal logistic regression models to compare COVID-19 severity by presence and specific site of metastatic cancer. They used logistic regression models to assess 30-day all-cause mortality. RESULTS: Compared to patients without metastasis, patients with metastases have increased hospitalization rates (59% vs. 49%) and higher 30 day mortality (18% vs. 9%). Patients with metastasis to bone, lung, liver, lymph nodes, and brain have significantly higher COVID-19 severity (adjusted odds ratios [ORs], 1.38, 1.59, 1.38, 1.00, and 2.21) compared to patients without metastases at those sites. Patients with metastasis to the lung have significantly higher odds of 30-day mortality (adjusted OR, 1.53; 95% confidence interval, 1.17-2.00) when adjusting for COVID-19 severity. CONCLUSIONS: Patients with metastatic cancer, especially with metastasis to the brain, are more likely to have severe outcomes after COVID-19 whereas patients with metastasis to the lung, compared to patients with cancer metastasis to other sites, have the highest 30-day mortality after COVID-19.

Oral antivirals for COVID-19 among patients with cancer.

Purpose: Immunocompromised individuals, such as those diagnosed with cancer, are at a significantly higher risk for severe illness and mortality when infected with SARS-CoV-2 (COVID-19) than the general population. Two oral antiviral treatments are approved for COVID-19: Paxlovid® (nirmatrelvir/ritonavir) and Lagevrio® (molnupiravir). There is a paucity of data regarding the benefit from these antivirals among immunocompromised patients with cancer, and recent studies have questioned their efficacy among vaccinated patients, even those with risk factors for severe COVID-19. Methods: We evaluated the efficacy and safety of nirmatrelvir/ritonavir and molnupiravir in preventing severe illness and death using our database of 457 patients with cancer and COVID-19 from Brown University-affiliated hospitals. 67 patients received nirmatrelvir/ritonavir or molnupiravir and were compared to 56 concurrent controls who received no antiviral treatment despite being eligible to receive it. Results: Administration of nirmatrelvir/ritonavir or molnupiravir was associated with improved survival and lower 90-day all-cause and COVID-19-attributed mortality (p<0.05) and with lower peak O2 requirements (ordinal odds ratio [OR] 1.52, 95% confidence interval [CI] 0.92-2.56). Conclusion: Acknowledging the small size of our sample as a limitation, we concluded that early antiviral treatment might be beneficial to immunocompromised individuals, particularly those with cancer, when infected with SARS-CoV-2. Larger-scale, well-stratified studies are needed in this patient population.

Outpatient anti-spike monoclonal antibody administration is associated with decreased morbidity and mortality among patients with cancer and COVID-19.

Patients with cancer have many comorbidities that increase their risk of death from Coronavirus disease 2019 (COVID-19). Anti-spike monoclonal antibodies (mAbs) reduce the risk of hospitalization or death from COVID-19 in the general population. To our knowledge, no studies have focused on the clinical efficacy of mAbs compared to no outpatient treatment exclusively among patients with solid tumors and hematologic malignancies, who are often excluded from clinical trials. We studied patients with cancer who had COVID-19 between 11.9.2020 and 7.21.2022 and received mAbs in an outpatient setting. We compared hospitalization and mortality rates to those of patients with cancer concurrently diagnosed with COVID-19, who were eligible for mAbs, but did not receive any outpatient treatment. 63 patients received mAbs and 89 no outpatient treatment. Administration of mAbs was associated with lower 90-day hospitalization (20.6% vs. 60.7%, p <0.001), all-cause (6.3% vs. 19.1%, p 0.025) and COVID-19-attributed (3.2% vs. 14.6%, p 0.019) mortality rates, and lower peak O2 requirements (ordinal Odds Ratio [OR] = 0.33, 95% Confidence Intervals [CI] = 0.20-0.53). Administration of mAbs (aHR 0.21, p <0.001), age (≥ 60 years, adjusted Hazard Ratio [aHR] 1.86, p=0.033), and metastases (aHR 0.41, p 0.007) were independently associated with hospitalization. mAb treatment remained significantly associated with all-cause (aHR 0.27, p 0.019) and COVID-19-attributed (aHR 0.19, p 0.031) mortality, after adjustment for other factors. mAb administration was associated with improved clinical outcomes among vulnerable patients with cancer and COVID-19. With no mAbs approved currently for treatment against the prevalent circulating variants, the development of new mAbs should be a research priority.

Outpatient anti-spike monoclonal antibody administration is associated with decreased morbidity and mortality among patients with cancer and COVID-19.

BACKGROUND: Patients with cancer have many comorbidities that increase their risk of death from Coronavirus disease 2019 (COVID-19). Anti-spike monoclonal antibodies (mAbs) reduce the risk of hospitalization or death from COVID-19 in the general population. To our knowledge, no studies have focused on the clinical efficacy of mAbs compared to no outpatient treatment exclusively among patients with solid tumors and hematologic malignancies, who are often excluded from clinical trials. METHODS: We studied patients with cancer who had COVID-19 between 11.9.2020 and 7.21.2022 and received mAbs in an outpatient setting. We compared hospitalization and mortality rates to those of patients with cancer concurrently diagnosed with COVID-19, who were eligible for mAbs, but did not receive any outpatient treatment. RESULTS: 63 patients received mAbs and 89 no outpatient treatment. Administration of mAbs was associated with lower 90-day hospitalization (20.6% vs. 60.7%, p<0.001), all-cause (6.3% vs. 19.1%, p=0.025) and COVID-19-attributed (3.2% vs. 14.6%, p=0.019) mortality rates, and lower peak O2 requirements (ordinal Odds Ratio [OR]=0.33, 95%Confidence Intervals [CI]=0.20-0.53). Administration of mAbs (aHR 0.21, p<0.001), age (≥ 60 years, adjusted Hazard Ratio [aHR] 1.86, p=0.033), and metastases (aHR 0.41, p=0.007) were independently associated with hospitalization. mAb treatment remained significantly associated with all-cause (aHR 0.27, p=0.019) and COVID-19-attributed (aHR 0.19, p=0.031) mortality, after adjustment for other factors. CONCLUSIONS: mAb administration was associated with improved clinical outcomes among vulnerable patients with cancer and COVID-19. With no mAbs approved currently for treatment against the prevalent circulating variants, the development of new mAbs should be a research priority.

Coinfections in Patients With Cancer and COVID-19: A COVID-19 and Cancer Consortium (CCC19) Study.

BACKGROUND: The frequency of coinfections and their association with outcomes have not been adequately studied among patients with cancer and coronavirus disease 2019 (COVID-19), a high-risk group for coinfection. METHODS: We included adult (≥18 years) patients with active or prior hematologic or invasive solid malignancies and laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection, using data from the COVID-19 and Cancer Consortium (CCC19, NCT04354701). We captured coinfections within ±2 weeks from diagnosis of COVID-19, identified factors cross-sectionally associated with risk of coinfection, and quantified the association of coinfections with 30-day mortality. RESULTS: Among 8765 patients (hospitalized or not; median age, 65 years; 47.4% male), 16.6% developed coinfections: 12.1% bacterial, 2.1% viral, 0.9% fungal. An additional 6.4% only had clinical diagnosis of a coinfection. The adjusted risk of any coinfection was positively associated with age >50 years, male sex, cardiovascular, pulmonary, and renal comorbidities, diabetes, hematologic malignancy, multiple malignancies, Eastern Cooperative Oncology Group Performance Status, progressing cancer, recent cytotoxic chemotherapy, and baseline corticosteroids; the adjusted risk of superinfection was positively associated with tocilizumab administration. Among hospitalized patients, high neutrophil count and C-reactive protein were positively associated with bacterial coinfection risk, and high or low neutrophil count with fungal coinfection risk. Adjusted mortality rates were significantly higher among patients with bacterial (odds ratio [OR], 1.61; 95% CI, 1.33-1.95) and fungal (OR, 2.20; 95% CI, 1.28-3.76) coinfections. CONCLUSIONS: Viral and fungal coinfections are infrequent among patients with cancer and COVID-19, with the latter associated with very high mortality rates. Clinical and laboratory parameters can be used to guide early empiric antimicrobial therapy, which may improve clinical outcomes.

Use of antibiotics is associated with worse clinical outcomes in patients with cancer treated with immune checkpoint inhibitors: A systematic review and meta-analysis.

OBJECTIVES: Observational and experimental studies suggest that the use of antibiotics close to administration of immune checkpoint inhibitors (ICI) can have a negative effect on tumour response and patient survival, due to microbiome dysbiosis and the resultant suppression of host immune response against neoplastic cells. METHODS: A systematic search of PUBMED and EMBASE was undertaken for studies published between 1 January 2017 and 1 June 2020, evaluating the association between the use of antibiotics and clinical outcomes in patients with cancer treated with ICIs. A meta-analysis of the association between the use of antibiotics and clinical outcomes was also performed. RESULTS: Forty-eight studies met the inclusion criteria (12,794 patients). Use of antibiotics was associated with shorter overall survival [hazard ratio (HR) 1.88, 95% confidence interval (CI) 1.59-2.22; adjusted HR 1.87, 95% CI 1.55-2.25] and progression-free survival (HR 1.52, 95% CI 1.36-1.70; adjusted HR 1.93, 95% CI 1.59-2.36), decreased response rate [odds ratio (OR) 0.54, 95% CI 0.34-0.86] and more disease progression (OR 2.00, 95% CI 1.27-3.14). The negative association between the use of antibiotics and progression-free survival was stronger in patients with renal cell carcinoma or melanoma compared with lung cancer. Only antibiotic administration >1 month prior to ICI initiation was associated with increased disease progression. Heterogeneity was substantial for all outcomes. CONCLUSIONS: Recent use of antibiotics in patients with cancer treated with ICIs was associated with worse clinical outcomes. Such patients may benefit from dedicated antimicrobial stewardship programmes.

Antifungal prophylaxis during 7 + 3 induction chemotherapy for acute myeloid leukemia is associated with improved survival, in a setting with low incidence of invasive mold infections.

Invasive fungal infections (IFIs) are a major cause of morbidity and mortality in patients undergoing induction chemotherapy for acute myeloid leukemia (AML). In this patient population, antifungal prophylaxis (AP) has been associated with decreased incidence of IFIs and better survival. However, some centers have not adopted AP during induction chemotherapy for AML, as it is unclear whether AP improves outcomes in settings where the incidence of invasive mold infections is low. We retrospectively assessed the differences in clinical outcomes and resource utilization in patients undergoing 7 + 3 induction chemotherapy for AML, after implementing a policy of AP as part of a dedicated inpatient malignant hematology service (HS) at Rhode Island Hospital. Between January 1, 2007 and April 1, 2019, 56 patients with AML received AP during 7 + 3 induction chemotherapy and 52 patients did not, without significant differences in their baseline characteristics. Use of AP was associated with less proven or probable IFI (0% vs. 6%, P = 0.1) and lower all-cause in-hospital mortality (7% vs. 21%, P < 0.05), without significant increases in resource utilization or toxicities. Empiric and targeted antifungal therapies were more frequently started in the non-AP group (69%) than changed in the AP group (41%, P < 0.005). Having a dedicated inpatient malignant hematology service was also associated with improved outcomes. However, use of AP was associated with better survival (30-day post-induction survival log-rank P < 0.05), prior to the implementation of this clinical service as well, which is suggestive of an independent benefit from AP.

Clinical experience with a novel assay measuring cytomegalovirus (CMV)-specific CD4+ and CD8+ T-cell immunity by flow cytometry and intracellular cytokine staining to predict clinically significant CMV events.

BACKGROUND: Cytomegalovirus (CMV) infection is one of the most common opportunistic infections following organ transplantation, despite administration of CMV prophylaxis. CMV-specific T-cell immunity (TCI) has been associated with reduced rates of CMV infection. We describe for the first time clinical experience using the CMV T-Cell Immunity Panel (CMV-TCIP), a commercially available assay which measures CMV-specific CD4+ and CD8+ T-cell responses, to predict clinically significant CMV events. METHODS: Adult (> 18-year-old) patients with CMV-TCIP results and ≥ 1 subsequent assessment for CMV DNAemia were included at Brown University and the University of Maryland Medical Center-affiliated hospitals between 4/2017 and 5/2019. A clinically significant CMV event was defined as CMV DNAemia prompting initiation of treatment. We excluded indeterminate results, mostly due to background positivity, allogeneic hematopoetic cell transplant (HCT) recipients, or patients who were continued on antiviral therapy against CMV irrespective of the CMV-TCIP result, because ongoing antiviral therapy could prevent a CMV event. RESULTS: We analyzed 44 samples from 37 patients: 31 were solid organ transplant recipients, 4 had hematologic malignancies, 2 had autoimmune disorders. The CMV-protection receiver operating characteristic (ROC) area under the curve (AUC) was significant for %CMV-specific CD4+ (AUC: 0.78, P < 0.001) and borderline for CD8+ (AUC: 0.66, P = 0.064) T-cells. At a cut-off value of 0.22% CMV-specific CD4+ T-cells, positive predictive value (PPV) for protection against CMV was 85% (95%CI 65-96%), and negative predictive value (NPV) was 67% (95%CI 41-87%). CONCLUSIONS: The CMV-TCIP, in particular %CMV-specific CD4+ T-cells, showed good diagnostic performance to predict CMV events. The CMV-TCIP may be a useful test in clinical practice, and merits further validation in larger prospective studies.