Seroconversion rate after vaccination against COVID-19 in patients with cancer-a systematic review.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has affected >210 million people worldwide. An optimal therapeutic approach for COVID-19 remains uncertain, to date. Since the history of cancer was linked to higher mortality rates due to COVID-19, the establishment of a safe and effective vaccine coverage is crucial in these patients. However, patients with cancer (PsC) were mostly excluded from vaccine candidates' clinical trials. This systematic review aims to investigate the current available evidence about the immunogenicity of COVID-19 vaccines in PsC. PATIENTS AND METHODS: All prospective studies that evaluated the safety and efficacy of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were included, with immunogenicity after the first and the second dose as the primary endpoint, when available. RESULTS: Vaccination against COVID-19 for PsC seems overall safe and immunogenic after well-conducted vaccination schedules. Yet the seroconversion rate remains lower, lagged or both compared to the general population. Patients with hematologic malignancies, especially those receiving B-cell-depleting agents in the past 12 months, are the most at risk of poor seroconversion. CONCLUSION: A tailored approach to vaccination may be proposed to PsC, especially on the basis of the type of malignancy and of the specific oncologic treatments received.

Impact of COVID-19 on ongoing oncological and hematological treatment strategy

Background: Outcomes and risk factors associated with COVID-19 worsening among cancer patients have previously been reported. However, the actual impact of SARs-Co-V2 infection on the cancer treatment strategy remains unknown. Here, we report the Gustave Roussy (GR) experience, one year after the onset of the pandemic focusing on the impact of COVID-19 in patients with ongoing management of oncohematological disease. Methods: All patients positively tested for SARS-CoV-2 and managed at GR between Mar 14th 2020 and Feb 15th 2021 (data cut-off) have been included. Patients underlying oncohematological disease and COVID19 characteristics have been collected. Cancer and COVID-19 management and outcomes have been assessed. Primary endpoint was the overall impact of COVID-19 on oncological and hematological treatment strategy assessed at 1, 3, 6 and 12 months. Results: At the time of the analysis, 423 patients (median age: 62 years) were found positive for SARS-CoV-2 and managed at GR with a median follow up of 5.6 months (0-13 months). Among them, 284 (67%) were admitted due to COVID-19. Clinical deterioration occurred in 87 patients (21%), 43 patients (10%) were transferred in intensive care unit and 123 (29%) patients died, among which 47 (11%) died from COVID-19. Overall, 329 (78%) patients were on active treatment for underlying oncohematological disease at time of COVID diagnosis. Impact of COVID-19 on cancer treatment strategy in those patients is presented in the Table. The majority (N=268, 81%) had no change in oncological strategy. For those who experienced a delay, median delay in treatment was 21 days (N=99, [1-77]), 30 days (N=15, [15-56]), 7 days (N=8,[3-35]) for systemic treatment, surgery and radiotherapy respectively. [Formula presented] Conclusions: COVID-19 outbreak is associated with a significant mortality in patients with cancer. However, for patients who did not die from COVID-19, we provide the first report supporting that ongoing treatment was maintained or could be resumed in the majority of cases in a timely manner. Legal entity responsible for the study: Gustave Roussy. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.

Sustained cancer clinical trial activity during the COVID-19 pandemic

Background: The COVID-19 pandemic deeply threatens the rigorous conduct of clinical trials, notably by delaying site initiation visits, patient enrolment, treatment administration, trial-associated procedures, and data monitoring. Unlike most other medical specialties, clinical trials are an integral part of patient care in oncology. Limiting access to clinical trials therefore results in a loss of chance for patients. Methods: In this retrospective single-center study, we collected clinical trial-specific items (including patient-related or trial management-related items) during the first pandemic wave (March– June 2020) and lockdown (March 17th-May 11th) at Gustave Roussy, and compared them to those of the same period in 2019. Results: In March 2020, 84 phase I (P1) and 210 phase II/III (P2/3) trials were open. During the first pandemic wave, 21 (25%) P1 and 20 (9%) P2/3 trials were temporarily halted, following a unilateral sponsor decision in virtually all cases;all but one were industry-sponsored. Despite this, all important metrics of the P1/2 trial activity remained similar to those of 2019, including the number of patients referred for inclusion (599 vs 620), inclusion consultations (215 vs 247), patients starting treatment (130 vs 130), Internal Review Board (IRB) submissions (14 vs 16), and site initiation visits (11 vs 15), all in 2020 vs 2019, respectively. The impact of the first lock-down was more marked on P2/3, with 152 patient inclusions (vs 346 in 2019), 125 randomizations (vs 278), 43 IRB submissions (vs 50) and 34 site initiation visits (vs 40). However, in parallel, 475 patients were included in three “COVID and cancer” trials. Among the 443 P1 and 2851 P2/3 patients, 198 and 628 COVID-19 PCR were performed internally, and five and 15 (2.5%) were positive, respectively. One patient with a community-based COVID-19 died after transfer in intensive care. Conclusions: Cancer clinical trials can, and must be maintained despite challenges brought by COVID-19. Sharing experiences and retrospectively evaluating the impact on patients’ safety and cancer-related outcomes will be critical to durably improve the clinical trials conduct and to anticipate at best challenges brought by future similar crises. Legal entity responsible for the study: Gustave Roussy. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.

Discovery of circulating biomarkers in COVID-19 patients undergoing anti-IL6R immunotherapy

Background: The severe pneumonitis in coronavirus disease 2019 (COVID-19) requires prolonged treatment in intensive care units, leading to overwhelmed hospital facilities. Treatment with tocilizumab (Actemra, Roche), a monoclonal antibody targeting interleukin 6 receptor (IL6R), has shown promising efficacy in alleviating the severe pneumonitis. However, only around 50% of the treated patients benefit from this intervention. It is therefore an unmet medical need to identify biomarkers associated with the severity of disease and theranostic biomarkers to predict and differentiate potential responders from non-responders to the treatment. Methods: An unbiased hyper reaction monitoring mass spectrometry (HRM™-MS) approach was used to analyze serum samples from severe COVID-19 cases before and 7 days after treatment with tocilizumab (n = 28), enabling simultaneous identification and quantification of all detectable serum proteins. All samples were measured using 1h gradient on a nano-flow LC-MS/MS setup operated in data-independent acquisition (DIA) mode. Data was extracted using Spectronaut™ (Biognosys). Univariate and multivariate statistical analyses were conducted to identify biomarker candidates. Pathway analysis was used to identify dysregulated biological functions and signaling pathways. Results: Over 450 proteins were quantified across all samples by HRM-MS. Univariate statistical analysis identified significantly changing proteins across conditions (mortality day 30, pre-post treatment, responder/non-responder, q-value > 0.05 and fold change >1.5). Multivariate analysis (PLS-DA) was also used to classify proteins based on their abundance across condition. Proteomic data was further integrated with clinical outcome data to identify a panel of protein biomarker candidates potentially useful in predicting tocilizumab treatment efficiency and the COVID-19 disease severity. Conclusions: Unbiased proteomic profiling of COVID-19 patient serum identified a panel of candidate protein biomarkers that associate with tocilizumab treatment response as well as the ensuing course of the disease. Further validation of these biomarker candidates opens the way for a personalized medicine approach in treating COVID-19. Legal entity responsible for the study: Biognosys AG. Funding: Biognosys AG. Disclosure: J-M. Michot;F-X. Danlos;F. Pommeret;A. Marabelle: Full/Part-time employment: Institut Gustave Roussy. V. Dozio;E. Kishazi;C. Escher;K. Kakalacheva - Beeler: Full/Part-time employment: Biognosys AG. M. Vasse;J. Rohmere;M. Roumier: Full/Part-time employment: Hôpital Foch.