Impact of chemotherapy and/or immunotherapy on neutralizing antibody response to SARS-CoV-2 mRNA-1237 vaccine in patients with solid tumors.

Patients with solid tumors have been a risk group since the beginning of the SARS-CoV-2 pandemic due to more significant complications, hospitalizations or deaths. The immunosuppressive state of cancer treatments or the tumor itself could influence the development of post-vaccination antibodies. This study prospectively analyzed 89 patients under chemotherapy and/or immunotherapy, who received two doses of the mRNA-1237 vaccine, and were compared with a group of 26 non-cancer individuals. Information on adverse events and neutralizing antibodies against the ancestral strain of SARS-CoV-2 (WH1) have been analyzed. Local reactions accounted for 65%, while systemic reactions accounted for 46% of oncologic individuals/cancer patients. Regarding the response to vaccination, 6.7% of cancer patients developed low neutralizing antibody levels. Lower levels of neutralizing antibodies between cancer and non-cancer groups were significant in individuals without previous SARS-CoV-2 infection, but not in previously infected individuals. We also observed that patients receiving chemotherapy or chemoimmunotherapy have significantly lower levels of neutralizing antibodies than non-cancer individuals. In conclusion, our study confirms the importance of prioritizing cancer patients receiving anticancer treatment in SARS-CoV-2 vaccination programs.

Anticancer Therapy and Mortality of Adult Patients with Hematologic Malignancy and COVID-19: A Systematic Review and Meta-Analysis.

Coronavirus disease 2019 (COVID-19) might affect cancer treatment outcomes. This systematic review and meta-analysis identified the prognostic predictors of adult patients with hematologic malignancies and COVID-19, and evaluated the effect of anticancer therapy on mortality. We performed a literature search of electronic databases and identified additional studies from the bibliographies of the articles that were retrieved. Two investigators independently extracted data according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. We evaluated study quality using the Newcastle-Ottawa Scale and performed a meta-analyses in order to evaluate the effect of anticancer therapy on mortality among adult patients with hematologic malignancies and COVID-19. Heterogeneity was assessed with the I2 statistic. The meta-analysis included 12 studies. The overall mortality rate was 36.3%. The pooled risk difference (RD) in mortality between patients receiving and not receiving anticancer therapy was 0.14 (95% confidence interval [CI]: 0.02-0.26; I2 = 76%). The pooled RD in mortality associated with chemotherapy was 0.22 (95% CI: 0.05-0.39; I2 = 48%), and with immunosuppression was 0.20 (95% CI: 0.05-0.34; I2 = 67%). In the subgroup analyses, anticancer-therapy-associated mortality was higher in females (RD = 0.57; 95% CI: 0.29-0.85; I2 = 0%) than in males (RD = 0.28; 95% CI: 0.04-0.52; I2 = 0%). Among patients with hematologic malignancies and COVID-19, those receiving anticancer therapy had a higher mortality risk, regardless of sex. The mortality risk was higher in females than in males. These results indicate that caution should be exercised when administering anticancer therapy to patients with hematologic malignancies and COVID-19.

Assessing the Acceptability of Home Blood Monitoring for Patients With Cancer Who Are Receiving Systemic Anticancer Therapy From a Patient, Caregiver, and Clinician Perspective: Focus Group and Interview Study.

BACKGROUND: Regular blood testing is an integral part of systemic anticancer therapy delivery. Blood tests are required before every administration of treatment to ensure that a patient is sufficiently well to receive it. Blood testing is burdensome for patients as they require either an extra visit within 48 hours of planned administration of treatment or a significantly long visit if performed on the day of treatment. The additional time for appointments can have a significant impact on the quality of life of someone who is living with cancer. In the United Kingdom, the COVID-19 pandemic created unprecedented disruption to the delivery of cancer care. Face-to-face hospital visits were reduced, resulting in the need to develop more innovative ways of working to minimize treatment interruptions. This led to significant uptake of digital technologies, with new models of care rapidly deployed across the UK health service to meet these challenges. OBJECTIVE: This study aimed to explore the acceptability of a point-of-care home blood monitoring device for people with cancer who are receiving systemic anticancer therapy, which is being developed in response to the increased need for remote care for patients with cancer. METHODS: Qualitative focus groups and semistructured interviews were conducted with patients (23/47, 49%), caregivers (6/47, 13%), and health care professionals (18/47, 38%) over a 19-month time frame from May 2019 to December 2020. Data were analyzed using framework analysis guided by the Unified Theory of Acceptance and Use of Technology model. RESULTS: Analysis identified 4 overarching themes: performance expectancy, effort expectancy, social influence, and facilitating conditions. CONCLUSIONS: This study found that patients with cancer, their caregivers, and health care professionals had positive perceptions about home blood monitoring. Although they are often considered synonymously, self-testing and self-management are not mutually exclusive, and this study illustrated some disparity in opinions regarding patient self-management. Home blood monitoring has the potential to provide patients with cancer with a convenient option for blood monitoring. It would minimize hospital attendances, decrease late treatment deferrals, and provide prompt recognition of cancer treatment toxicities, thus enhancing the existing nurse-led protocols and clinical pathways. Home blood monitoring would create a long-term sustainable transformation for the delivery of cancer care, using digital health to act as a facilitator to address a pertinent issue regarding improving the efficiency of hospital resources and increasing the delivery of personalized patient care. Further studies are needed to determine how and where home blood monitoring would fit within clinical pathways, in a way that is robust and equitable.

Targeting CD38 in Neoplasms and Non-Cancer Diseases.

CD38 is a myeloid antigen present both on the cell membrane and in the intracellular compartment of the cell. Its occurrence is often enhanced in cancer cells, thus making it a potential target in anticancer therapy. Daratumumab and isatuximab already received FDA approval, and novel agents such as MOR202, TAK079 and TNB-738 undergo clinical trials. Also, novel therapeutics such as SAR442085 aim to outrank the older antibodies against CD38. Multiple myeloma and immunoglobulin light-chain amyloidosis may be effectively treated with anti-CD38 immunotherapy. Its role in other hematological malignancies is also important concerning both diagnostic process and potential treatment in the future. Aside from the hematological malignancies, CD38 remains a potential target in gastrointestinal, neurological and pulmonary system disorders. Due to the strong interaction of CD38 with TCR and CD16 on T cells, it may also serve as the biomarker in transplant rejection in renal transplant patients. Besides, CD38 finds its role outside oncology in systemic lupus erythematosus and collagen-induced arthritis. CD38 plays an important role in viral infections, including AIDS and COVID-19. Most of the undergoing clinical trials focus on the use of anti-CD38 antibodies in the therapy of multiple myeloma, CD19- B-cell malignancies, and NK cell lymphomas. This review focuses on targeting CD38 in cancer and non-cancerous diseases using antibodies, cell-based therapies and CD38 inhibitors. We also provide a summary of current clinical trials targeting CD38.

Cyclophilin A/CD147 Interaction: A Promising Target for Anticancer Therapy.

Cyclophilin A (CypA), which has peptidyl-prolyl cis-trans isomerase (PPIase) activity, regulates multiple functions of cells by binding to its extracellular receptor CD147. The CypA/CD147 interaction plays a crucial role in the progression of several diseases, including inflammatory diseases, coronavirus infection, and cancer, by activating CD147-mediated intracellular downstream signaling pathways. Many studies have identified CypA and CD147 as potential therapeutic targets for cancer. Their overexpression promotes growth, metastasis, therapeutic resistance, and the stem-like properties of cancer cells and is related to the poor prognosis of patients with cancer. This review aims to understand the biology and interaction of CypA and CD147 and to review the roles of the CypA/CD147 interaction in cancer pathology and the therapeutic potential of targeting the CypA/CD147 axis. To validate the clinical significance of the CypA/CD147 interaction, we analyzed the expression levels of PPIA and BSG genes encoding CypA and CD147, respectively, in a wide range of tumor types using The Cancer Genome Atlas (TCGA) database. We observed a significant association between PPIA/BSG overexpression and poor prognosis, such as a low survival rate and high cancer stage, in several tumor types. Furthermore, the expression of PPIA and BSG was positively correlated in many cancers. Therefore, this review supports the hypothesis that targeting the CypA/CD147 interaction may improve treatment outcomes for patients with cancer.

Accurate Triage of Oncological Patients for Safely Continuing Cancer Therapy During the SARS-CoV-2 Pandemic.

OBJECTIVE: To evaluate the efficacy of clinical triage of oncological patients for safe continuation of cancer therapy implemented during the first SARS-CoV-2 outbreak. METHODS: Between 25 February and 21 April 2020, patients attending the Medical Oncology Unit, Spedali Civili Hospital, Brescia (Italy) for cancer therapy underwent triage to identify those with no signs and symptoms suspicious for SARS-CoV-2 infection in which antineoplastic treatment could be continued as scheduled. Triage questions investigated common symptoms (e.g., fever, cough, dyspnea, anosmia, dysgeusia, headache, nasal congestion, conjunctival congestion, sore throat, diarrhea, nausea and vomiting); body temperature and pulse oximetry were also recorded. All patients were followed-up for overt SARS-CoV-2 through to 18th May 2020. RESULTS: Overall, 1180 patients (median age 65 years) underwent triage during the study period. The most frequent primary malignances were breast (32%), gastrointestinal (18%), and lung (16.5%) cancer. Thirty-one (2.5%) presented with clinically evident SARS-CoV-2 infection and tested positive on nasopharyngeal swab testing and/or radiological imaging. Triage identified 69 (6%) grey zone patients with symptoms suspicious for SARS-CoV-2; 5 (7.2%) subsequently developed symptomatic disease. Neither the symptomatic nor the grey zone patients received their scheduled treatment; instead, they were referred for hospitalization or home quarantine. CONCLUSION: Triage of oncological patients at our Unit provided for safe continuation of scheduled cancer treatment in 91.5% of patients during the initial SARS-CoV-2 outbreak.

Lung cancer patients with COVID-19 in Spain: GRAVID study.

INTRODUCTION: Patients with cancer may be at increased risk of more severe COVID-19 disease; however, prognostic factors are not yet clearly identified. The GRAVID study aimed to describe clinical characteristics, outcomes, and predictors of poor outcome in patients with lung cancer and COVID-19. METHODS: Prospective observational study that included medical records of patients with lung cancer and PCR-confirmed COVID-19 diagnosis across 65 Spanish hospitals. The primary endpoint was all-cause mortality; secondary endpoints were hospitalization and admission to intensive care units (ICU). RESULTS: A total of 447 patients with a mean age of 67.1 ± 9.8 years were analysed. The majority were men (74.3 %) and current/former smokers (85.7 %). NSCLC was the most frequent type of cancer (84.5 %), mainly as adenocarcinoma (51.0 %), and stage III metastatic or unresectable disease (79.2 %). Nearly 60 % of patients were receiving anticancer treatment, mostly first-line chemotherapy. Overall, 350 (78.3 %) patients were hospitalized for a mean of 13.4 ± 11.4 days, 9 (2.0 %) were admitted to ICU and 146 (32.7 %) died. Advanced disease and the use of corticosteroids to treat COVID-19 during hospitalization were predictors of mortality. Hospitalized, non-end-of-life stage patients with lymphocytopenia and high LDH had an increased risk of death. Severity of COVID-19 correlated to higher mortality, ICU admission, and mechanical ventilation rates. CONCLUSIONS: Mortality rate was higher among patients treated with corticosteroids during hospitalization, while anticancer therapy was not associated with an increased risk of hospitalization or death. Tailored approaches are warranted to ensure effective cancer management while minimizing the risk of exposure to SARS-CoV-2.

Association of clinical factors and recent anticancer therapy with COVID-19 severity among patients with cancer: a report from the COVID-19 and Cancer Consortium.

BACKGROUND: Patients with cancer may be at high risk of adverse outcomes from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We analyzed a cohort of patients with cancer and coronavirus 2019 (COVID-19) reported to the COVID-19 and Cancer Consortium (CCC19) to identify prognostic clinical factors, including laboratory measurements and anticancer therapies. PATIENTS AND METHODS: Patients with active or historical cancer and a laboratory-confirmed SARS-CoV-2 diagnosis recorded between 17 March and 18 November 2020 were included. The primary outcome was COVID-19 severity measured on an ordinal scale (uncomplicated, hospitalized, admitted to intensive care unit, mechanically ventilated, died within 30 days). Multivariable regression models included demographics, cancer status, anticancer therapy and timing, COVID-19-directed therapies, and laboratory measurements (among hospitalized patients). RESULTS: A total of 4966 patients were included (median age 66 years, 51% female, 50% non-Hispanic white); 2872 (58%) were hospitalized and 695 (14%) died; 61% had cancer that was present, diagnosed, or treated within the year prior to COVID-19 diagnosis. Older age, male sex, obesity, cardiovascular and pulmonary comorbidities, renal disease, diabetes mellitus, non-Hispanic black race, Hispanic ethnicity, worse Eastern Cooperative Oncology Group performance status, recent cytotoxic chemotherapy, and hematologic malignancy were associated with higher COVID-19 severity. Among hospitalized patients, low or high absolute lymphocyte count; high absolute neutrophil count; low platelet count; abnormal creatinine; troponin; lactate dehydrogenase; and C-reactive protein were associated with higher COVID-19 severity. Patients diagnosed early in the COVID-19 pandemic (January-April 2020) had worse outcomes than those diagnosed later. Specific anticancer therapies (e.g. R-CHOP, platinum combined with etoposide, and DNA methyltransferase inhibitors) were associated with high 30-day all-cause mortality. CONCLUSIONS: Clinical factors (e.g. older age, hematological malignancy, recent chemotherapy) and laboratory measurements were associated with poor outcomes among patients with cancer and COVID-19. Although further studies are needed, caution may be required in utilizing particular anticancer therapies. CLINICAL TRIAL IDENTIFIER: NCT04354701.

Has the COVID-19 Pandemic Increased Mortality Among Patients with Cancer Receiving Systemic Anticancer Treatments?

OBJECTIVE: To evaluate the mortality rates in patients receiving anticancer therapy in the coronavirus disease-19 (COVID-19) pandemic period. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Department of Medical Oncology, Sakarya University Training and Research Hospital, Sakarya, Turkey, from December 2017 to May 2020. METHODOLOGY: Only patients who received chemotherapy and immunotherapy were selected and enrolled in the study. All patients (n=3,204) were divided into three groups, namely the first group (1st December 2017-31st May 2018, n=918), second group (1st December 2018-31st May 2019, n=1,147), and the pandemic period group (PPG) (1st December 2019-31st May 2020, n=1,139), according to the period during which they received anticancer treatment. The clinical and demographic characteristics and mortality rates of these three groups of patients were compared. RESULTS: The median age of the total of 3,204 patients was 61 (53-69). In this study, 51.1% (n=1,636) were females and 48.9% were males. The mortality rates were 13.5% (n=124) in the first group, 13.4% (n=154) in the second group, and 13.0% (n=148) in the PPG, respectively. Overall mortality rates did not differ among patients with cancer in the three different six-month periods analysed (p = 0.931). CONCLUSION: There was no unexpected increased in mortality rate among patients undergoing cancer therapy during the COVID-19 pandemic as compared to the previous years of the same timeline. No increase in monthly mortality rates among patients receiving anti-cancer treatment were demonstrated during the pandemic period.

How Fear of COVID-19 Can Affect Treatment Choices for Anaplastic Large Cell Lymphomas ALK+ Therapy: A Case Report.

BACKGROUND: The t (2; 5) chromosomal rearrangement of the ALK gene with nucleophosmin 1 gene (NPM1), resulting in an NPM1-ALK fusion, was first demonstrated in 1994 in anaplastic large cell lymphoma, (ALCL), a T-cell lymphoma responsive to cyclophosphamide, abriblastine, vincristine and prednisone in approximately 80% of cases; refractory cases usually respond favorably to brentuximab vedotin. These treatments are regarded as a bridge to allogeneic hematopoietic stem cell transplantation (allo-SCT). Nowadays, transplant procedures and the monitoring of chemotherapy patients proceed very slowly because the SARS-CoV-2 pandemic has heavily clogged the hospitals in all countries. RESULTS: A 40-year-old Caucasian woman was first seen at our clinical center in June 2020. She had ALCL ALK+, a history of failure to two previous therapeutic lines and was in complete remission after 12 courses of brentuximab, still pending allo-SCT after two failed donor selections. Facing a new therapeutic failure, we requested and obtained authorization from the Italian drug regulatory agency to administer 250 mg of crizotinib twice a day, a drug incomprehensibly not registered for ALCL ALK +. CONCLUSIONS: The response to crizotinib was optimal since no adverse event occurred, and CT-PET scans persisted negative; this drug has proved to be a valid bridge to allo-SCT.

Rescue Therapy of Refractory Diffuse Large B-Cell Lymphomas BCL2 with Venetoclax: Case Report.

Eleven years ago, a 64-year-old Caucasian man had LNH Follicular 3a, IV A stage, FLIPI 2 as a prognostic index of follicular lymphoma. He received 8 cycles of RCHOP followed by rituximab maintenance, with complete remission. Due to a systemic recurrence, a new treatment schedule (RCOMP, 6 cycles) was introduced with partial remission persisting during a long-term maintenance treatment with rituximab. Three years ago, LNH Follicular 3a progressed into GC type diffuse large B-cell lymphomas (DLBCL); 6 cycles of rituximab and bendamustine were followed by R-ICE and R OXALI DHAP treatments without beneficial effect. Due to the worse general condition (ECOG 3-4), the patient was treated with pixantrone (6 cycles) until July 10, 2019, with a partial response. On Jan 13, 2020, an extreme compassioned treatment with venetoclax alone was started; this drug was well tolerated and provided a satisfactory clinical and laboratory improvement. In June 2020, however, he developed bone marrow toxicity and septic fever. Nasal and pharyngeal secretions were SARS-CoV-2 RNA negative. Blood cultures for mycotic agents and Gram-positive, Gram-negative, and anaerobic bacteria were negative, but few days later, the patients died of sepsis due to unidentified agents. The use of venetoclax as a single drug to treat DLBCL BCL2 patients deserves further investigation.

COVID-19 and Oncology: Service transformation during pandemic.

BACKGROUND: The COVID-19 pandemic has challenged healthcare systems around the world, where resources have refocused on increasing critical bed capacity to prepare for the peak in incidence of COVID-19. Oncology faces an unprecedented challenge as patients require multidisciplinary care and are more likely to be immunosuppressed. Services in oncology have been transformed using minimal resources over a short period of time. This transformation continues and telemedicine is playing a key role. AIMS: We explore how services in oncology have transformed to deliver services including consultations, systemic anticancer therapy, and surgery for patients, while shielding them from contracting COVID-19. We assess the risks and benefits of the service transformation in the immediate, interim, and long term, and how telemedicine supports the process. METHODS: We performed a comprehensive review of the literature using suitable keywords on the search engines of PubMed, SCOPUS, Google Scholar, and latest official data from May to June 2020. RESULTS: Through the published literature on this topic, we discuss the transformations in oncology and the impact on patients and healthcare workers due to the COVID-19 pandemic. We reflect on the lessions from COVID-19 and assess the role of telemedicine in the future of oncology services. CONCLUSION: Transformation of services in oncology effectively shields patients from COVID-19 infections, and telemedicine plays a role in virtual consultations. The long-term effects are yet to be seen, such as safety of home-based treatment, and effectiveness of virtual communication on patient care. As oncology requires a multidisciplinary approach, telemedicine will play a key role to improve patient-centered cancer care in the future.

Defining the true impact of coronavirus disease 2019 in the at-risk population of patients with cancer.

BACKGROUND: In light of the coronavirus disease 2019 (COVID-19) pandemic, cancer centres in the United Kingdom and Europe re-organised their services at an unprecedented pace, and many patients with cancer have had their treatments severely disrupted. Patients with cancer were considered at high risk on sparse evidence, and despite a small number of emerging observational studies, the true incidence and impact of COVID-19 in the 'at-risk' population of patients with cancer is yet to be defined. METHODS: Epidemiological and clinical data were collected prospectively for patients attending the Royal Marsden Hospital and three network hospitals between March 1st and April 30th 2020 that were confirmed to have Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection. Significance of clinical and pathological characteristics was assessed using the Fisher's exact test and Wilcoxon rank sum test, whilst univariate and multivariate logistic regression models were used to further assess risk. The number of patients attending in March/April 2020 for face-to-face attendances was also extracted. FINDINGS: During the 2-month study period, 867 of 13,489 (6.4%) patients met the criteria leading to swab testing. Of the total at-risk population, only 113 of 13,489 (0.84%) were swab positive, 101 of 13,489 (0.75%) required hospital admission and 29 of 13,489 (0.21%) died of COVID-19. Of the patients that attended the hospital to receive cytotoxic chemotherapy alone or in combination with other therapy, 59 of 2001 (2.9%) were admitted to the hospital for COVID-19-related issues and 20 of 2001 (1%) died. Of the patients that collected targeted treatments, 16 of 1126 (1.4%) were admitted and 1 of 1126 (0.1%) died. Of the 11 patients that had received radiotherapy, 6 of 1042 (0.6%) required inpatient admission and 2 of 1042 (0.2%) died. INTERPRETATIONS: Administration of systemic anticancer therapy appears to be associated with a modest risk of severe COVID-19 infection. Based on this snapshot taken as the first wave of COVID-19 hit our practice, we conclude that continuation of active cancer treatment, even in the palliative setting, is appropriate.