ABSTRACT
Background: The Omicron (B.1.1.529) SARS-CoV-2 variant is highly transmissible and escapes vaccinal immunity. Evidence is lacking as to the impact of Omicron in oncological patients. Method(s): Capitalizing on OnCovid study data (NCT04393974), we analysed COVID-19 morbidity and case fatality rate at 28 days (CFR28) of unvaccinated patients across 3 phases defined following the evolution of the pandemic in Europe, according to date of COVID-19 diagnosis: "Pre-vaccination" phase (27/02/2020-30/11/2020), "Alpha- Delta variant" phase (01/12/2020-14/12/2021), "Omicron variant" phase (15/12/2021-31/01/2022). Finding(s): By the data lock of 04/02/2022, 3820 patients from 37 institutions across 6 countries were entered. Out of 3473 eligible patients, 2033 (58.6%), 1075 (30.9%) and 365 (10.5%) were diagnosed during the Pre-vaccination, Alpha-Delta and Omicron phases. In total 659 (61.3%) and 42 (11.5%) were unvaccinated in the Alpha-Delta and Omicron. Unvaccinated patients across the Omicron, Alpha-Delta and Pre-vaccination phases experienced similar CFR28 (27.5%, 28%, 29%, respectively). Following propensity score matching, 42 unvaccinated Omicron patients were matched with 122 and 121 patients from the Pre-vaccination and Alpha-Delta phases respectively, based on country of origin, sex, age, comorbidity burden, primary tumour, cancer stage and status, and the receipt of systemic anticancer therapy at COVID-19. Unvaccinated Omicron patients experienced improved COVID-19 outcomes in comparison to patients diagnosed during the Prevaccination phase. Morbidity and mortality were comparable to those of unvaccinated patients diagnosed during the Alpha-Delta phase. Interpretation(s): Despite time-dependent improvements in outcomes reported in the Omicron phase, patients with cancer remain highly vulnerable to SARS-CoV-2 in absence of vaccinal protection. This study provides unequivocal evidence in support of universal vaccination of patients with cancer as a protective measure against morbidity and mortality from COVID-19.
ABSTRACT
Background: Durable clinical benefit has been achieved with nivolumab (NIVO) + ipilimumab (IPI), including an overall survival (OS) of 49% and a melanoma-specific survival (MSS) of 56%, with median MSS not reached (NR) at 6.5-y minimum follow-up. Here we report sustained efficacy outcomes at 7.5 y. Methods: Patients (pts) with previously untreated, unresectable stage III/IV melanoma were randomly assigned 1:1:1 and stratified by PD-L1 status, BRAF mutation status, and metastasis stage to receive NIVO 1 mg/kg + IPI 3 mg/kg for 4 doses Q3W, followed by NIVO 3 mg/kg Q2W (n = 314);NIVO 3 mg/kg Q2W + placebo (n = 316);or IPI 3 mg/kg Q3W for 4 doses + placebo (n = 315) until progression or unacceptable toxicity. Co-primary endpoints were progression-free survival (PFS) and OS with NIVO + IPI or NIVO alone versus IPI. Results: With a minimum follow-up of 7.5 y, median OS remained stable at 72.1 mo (NIVO + IPI), 36.9 mo (NIVO), and 19.9 mo (IPI);median MSS was NR, 49.4 mo, and 21.9 mo, respectively (Table). While the objective response rate remained stable at 58% (NIVO + IPI), 45% (NIVO), and 19% (IPI), median duration of response had now been reached for NIVO at 90.8 mo and remains NR and 19.2 mo for NIVO + IPI and IPI, respectively. Subsequent systemic therapy was received by 36%, 49%, and 66% of NIVO + IPI-, NIVO-, and IPI-treated patients, respectively, and median time to that therapy was NR (95% CI, 45.9-NR), 24.7 mo (16.0-38.7), and 8.0 mo (6.5-8.7). Of patients alive at 7.5 y, 106/138 (77%, NIVO + IPI), 80/115 (70%, NIVO), and 27/60 (45%, IPI) were off treatment and had never received subsequent systemic therapy. No change to the safety summary was observed with additional follow-up;updated health-related quality of life data will be reported. Of the 10 new deaths since the 6.5-y follow-up (ie, 5 NIVO + IPI;3 NIVO;2 IPI), none were treatment-related;4 were due to melanoma progression;1 was due to an unknown cause;and 5 were due to other causes, but not associated with a COVID diagnosis. Conclusions: The 7.5-y follow-up continues to demonstrate the durability of responses with NIVO + IPI and an ongoing survival plateau. A substantial difference in median OS and MSS between patients treated with NIVO + IPI or NIVO was observed in descriptive analyses.
ABSTRACT
Background: The long-term impact of COVID-19 in cancer patients (pts) is undefined. Methods: Among 2795 consecutive pts with COVID-19 and cancer registered to OnCovid between 01/2020 and 02/2021, we examined clinical outcomes of pts reassessed post COVID-19 recovery. Results: Among 1557 COVID-19 survivors, 234 (15%) reported sequelae including respiratory symptoms (49.6%), fatigue (41%) and cognitive/psychological dysfunction (4.3%). Persisting COVID-19 sequelae were more likely found in males (p=0.0407) aged ≥65 years (p=0.0489) with ≥2 comorbidities (p=0.0006) and positive smoking history (p=0.0004). Sequelae were associated with history of prior hospitalisation (p<0.0001), complicated disease (p<0.0001) and COVID-19 therapy (p=0.0002). With a median post-COVID-19 follow up of 128 days (95%CI 113-148), multivariable analysis of survival revealed COVID-19 sequelae to be associated with an increased risk of death (HR 1.76, 95%CI 1.16-2.66) after adjusting for sex, age, comorbidities, tumour characteristics, anticancer therapy and COVID-19 severity. Out of 473 patients who were on systemic anticancer therapy (SACT) at COVID-19 diagnosis;62 (13.1%) permanently discontinued therapy and 75 (15.8%) received SACT adjustments, respectively. Discontinuations were due to worsening performance status (45.1%), disease progression (16.1%) and residual organ disfunction (6.3%). SACT adjustments were pursued to avoid hospital attendance (40%), prevent immunosuppression (57.3%) or adverse events (20.3%). Multivariable analyses showed permanent discontinuation to be associated with an increased risk of death (HR 4.2, 95%CI: 1.62-10.7), whereas SACT adjustments did not adversely affect survival. Conclusions: Sequelae post-COVID-19 affect up to 15% of patients with cancer and adversely influence survival and oncological outcomes after recovery. SACT adjustments can be safely pursued to preserve oncological outcomes in patients who remain eligible to treatment.
ABSTRACT
Background: There are many assumptions that raise fears of auto-immune toxicity of SARS-COV-2 vaccine in patients affected by Thymic epithelial tumours (TETs). TETs are associated with paraneoplastic autoimmune disorders and vaccine autoimmune cross reactivity is associated with many syndromes such as Guillain-Barre, multiple sclerosis, demyelinating neuropathies. Moreover, a crossreaction between SARS-Cov-2 anti protein spike antibodies and several tissue proteins has been reported. Material and methods: We are prospectively collecting data on safety and new onset or recurrence of autoimmune disorders in patients with TETs who received SARSCOV- 2 vaccine and are treated in referral centres of the TYME network. Patients with both Thymoma [T] and Thymic carcinoma [TC], with and without pre-existing autoimmune disorders, treated with chemotherapy, immunotherapy, TKI or just in follow up are included in the analysis. Association between epidemiological-clinical factors and risk of general Adverse Events (AEs), immune-related AEs and worsening of autoimmune disorders will be assessed. Results: Preliminary data from the first 20 patients (14 TC and 4 T) suggest that the administration of SARSCOV- 2 vaccines is well tolerated, with no safety signals nor reactivation or new onset of autoimmune diseases observed. Prospective data collection of all TETs patients treated in referral centres of the TYME network is ongoing and will be presented at the time of AIOM congress. Conclusions: Preliminary data suggest that the administration of SARS-COV-2 vaccines is safe and well tolerated in patients affected by TETs. A comprehensive characterization of general and immune-related safety profile of SARSCOV- 2 vaccines in such rare oncological population, enriched for potential risk factors for AEs, is ongoing.
ABSTRACT
Background: The long-term impact of COVID-19 in cancer patients (pts) is undefined. Methods: Among 2795 consecutive pts with COVID-19 and cancer registered to OnCovid between 01/2020 and 02/2021, we examined clinical outcomes of pts reassessed post COVID-19 recovery. Results: Among 1557 COVID-19 survivors, 234 (15%) reported sequelae including respiratory symptoms (49.6%), fatigue (41%) and cognitive/psychological dysfunction (4.3%). Persisting COVID-19 sequelae were more likely found in males (p=0.0407) aged ≥65 years (p=0.0489) with ≥2 comorbidities (p=0.0006) and positive smoking history (p=0.0004). Sequelae were associated with history of prior hospitalisation (p<0.0001), complicated disease (p<0.0001) and COVID-19 therapy (p=0.0002). With a median post-COVID-19 follow up of 128 days (95%CI 113-148), multivariable analysis of survival revealed COVID-19 sequelae to be associated with an increased risk of death (HR 1.76, 95%CI 1.16-2.66) after adjusting for sex, age, comorbidities, tumour characteristics, anticancer therapy and COVID-19 severity. Out of 473 patients who were on systemic anticancer therapy (SACT) at COVID-19 diagnosis;62 (13.1%) permanently discontinued therapy and 75 (15.8%) received SACT adjustments, respectively. Discontinuations were due to worsening performance status (45.1%), disease progression (16.1%) and residual organ disfunction (6.3%). SACT adjustments were pursued to avoid hospital attendance (40%), prevent immunosuppression (57.3%) or adverse events (20.3%). Multivariable analyses showed permanent discontinuation to be associated with an increased risk of death (HR 4.2, 95%CI: 1.62-10.7), whereas SACT adjustments did not adversely affect survival. Conclusions: Sequelae post-COVID-19 affect up to 15% of patients with cancer and adversely influence survival and oncological outcomes after recovery. SACT adjustments can be safely pursued to preserve oncological outcomes in patients who remain eligible to treatment. Clinical trial identification: NCT04393974. Legal entity responsible for the study: Imperial College London. Funding: Has not received any funding. Disclosure: A. Cortellini: Financial Interests, Personal, Advisory Board: MSD;Financial Interests, Personal, Advisory Board: BMS;Financial Interests, Personal, Advisory Board: Roche;Financial Interests, Personal, Invited Speaker: Novartis;Financial Interests, Personal, Invited Speaker: AstraZeneca;Financial Interests, Personal, Invited Speaker: Astellas;Financial Interests, Personal, Advisory Board: Sun Pharma. D.J. Pinato: Financial Interests, Personal, Advisory Board: ViiV Healthcare;Financial Interests, Personal, Invited Speaker: Bayer;Financial Interests, Personal, Advisory Board: Eisai;Financial Interests, Personal, Invited Speaker: Roche;Financial Interests, Personal, Invited Speaker: AstraZeneca. All other authors have declared no conflicts of interest.
ABSTRACT
Background: ICI are widely used in the treatment of various cancer types. It has been hypothesized that ICI couldconfer an increased risk of severe acute lung injury or other complications associated with severe acute respiratorysyndrome coronavirus 2 (SARS-CoV-2). Methods: We analyzed data from 113 patients with laboratory-confirmed COVID-19 while on treatment with ICI without chemotherapy in 19 hospitals in North America, Europe, and Australia. Data collected included details onsymptoms, comorbidities, medications, treatments and investigations for COVID-19, and outcomes (hospitaladmission, ICU admission, and mortality). Results: The median age was 63 years (range 27-86);40 (35%) patients were female. Most common malignancies were melanoma (n=64, 57%), non-small cell lung cancer (n=19, 17%), and renal cell carcinoma (n=11, 10%);30(27%) patients were treated for early (neoadjuvant/adjuvant) and 83 (73%) for advanced cancer. Most patientsreceived anti-PD-1 (n=85, 75%), combination anti-PD-1 and anti-CTLA-4 (n=15, 13%), or anti-PD-L1 (n=8, 7%) ICI.Comorbidities included cardiovascular disease (n=31, 27%), diabetes (n=17, 15%), and pulmonary disease (n=14, 12%). Symptoms were present in 68 (60%) patients;46 (68%) had fever, 40 (59%) cough, and 23 (34%) dyspnea.Overall, ICI was interrupted in 58 (51%) patients. At data cutoff, 33 (29%) patients were admitted to hospital, 6 (5%)to ICU, and 9 (8%) patients died. COVID-19 was the primary cause of death in 7 patients, 3 of whom were admittedto ICU. Cancer types in patients who died were melanoma (2), non-small cell lung cancer (2), renal cell carcinoma(2), and others (3);all (9) patients had advanced cancer. Administered treatments were oxygen therapy (8), mechanical ventilation (2), vasopression (2), antibiotics (7), antiviral drugs (4), glucocorticoids (2), and anti-IL-6 (2).Of all hospitalized patients, 20 (61%) had been discharged and 4 (12%) were still in hospital at data cutoff. Conclusion: The mortality rate of COVID-19 in patients on ICI is higher than rates reported for the generalpopulation without comorbidities but may not be higher than rates reported for the cancer population. Despite thesepreliminary findings, COVID-19 patients on ICI may not have symptoms and a proportion may continue ICI.Correlative analyses are ongoing and will be presented.