Sotrovimab restores neutralisation against current Omicron subvariants in patients with blood cancer

Wu et al. report that patients with hematologic malignancies have reduced immunity against SARS-CoV-2 Omicron subvariants and Sotrovimab retains neutralizing capacity against all tested Omicron subvariants.

Functional immune responses against SARS-CoV-2 variants of concern after fourth COVID-19 vaccine dose or infection in patients with blood cancer.

Patients with blood cancer continue to have a greater risk of inadequate immune responses following three COVID-19 vaccine doses and risk of severe COVID-19 disease. In the context of the CAPTURE study (NCT03226886), we report immune responses in 80 patients with blood cancer who received a fourth dose of BNT162b2. We measured neutralizing antibody titers (NAbTs) using a live virus microneutralization assay against wild-type (WT), Delta, and Omicron BA.1 and BA.2 and T cell responses against WT and Omicron BA.1 using an activation-induced marker (AIM) assay. The proportion of patients with detectable NAb titers and T cell responses after the fourth vaccine dose increased compared with that after the third vaccine dose. Patients who received B cell-depleting therapies within the 12 months before vaccination have the greatest risk of not having detectable NAbT. In addition, we report immune responses in 57 patients with breakthrough infections after vaccination.

A pilot of Blood-First diagnostic cell free DNA (cfDNA) next generation sequencing (NGS) in patients with suspected advanced lung cancer.

INTRODUCTION: The diagnostic pathway for lung cancer can be long. Availability of front-line targeted therapies for NSCLC demands access to good quality tissue for genomic sequencing and rapid reporting of results. Diagnosis of lung cancer and availability of tissue was delayed during the COVID-19 pandemic. METHODS: A pilot study assessing Guardant360™ cfDNA-NGS in patients with radiological-suspected advanced-stage lung cancer was performed at an academic cancer centre during COVID-19. Variants were tiered using AMP/ASCO/CAP guidelines and discussed at a tumour molecular board. The primary endpoint was the proportion of patients who commenced targeted treatment based on cfDNA-NGS results without tissue molecular results, predicted to be ≥ 10%. RESULTS: Between April 2020-May 2021, 51 patients were enrolled; 49 were evaluable. The median age was 71 years, 43% were never-smokers, 86% had stage IV disease. 80% of evaluable cfDNA-NGS were informative (tumour-derived cfDNA detected). cfDNA-NGS detected 30 (61%) AMP/ASCO/CAP tier 1 variants, including 20 additional tier 1 variants compared to tissue testing. Three patients with non-informative cfDNA-NGS had tier 1 variants identified on tissue testing. Eleven (22%; 95%CI 12%-27%) patients commenced targeted therapy based on cfDNA-NGS results without tissue molecular results, meeting the primary endpoint. Median time to results was shorter for cfDNA-NGS compared to standard-of-care tissue tests (9 versus 25 days, P < 0.0001). CONCLUSION: Blood-first cfDNA-NGS in NSCLC patients increased the breadth and rapidity of detection of actionable variants with high tissue concordance and led to timely treatment decisions. A blood-first approach should be considered to improve the speed and accuracy of therapeutic decision-making.

Safety monitoring of two and four-weekly adjuvant durvalumab for patients with stage III NSCLC: implications for the COVID-19 pandemic and beyond.

Durvalumab is the first approved adjuvant immunotherapy agent for patients with stage III NSCLC treated with concurrent chemoradiotherapy and is associated with improved overall survival. In order to minimise the number of hospital visits for patients receiving durvalumab during the COVID-19 pandemic we implemented 4-weekly (20 mg/kg) durvalumab in place of 2-weekly infusions at The Royal Marsden Hospital. We assessed the potential impact of the safety of a 4-weekly schedule in patients receiving adjuvant durvalumab. We carried out a retrospective study of 40 patients treated with 2-weekly and 4-weekly infusions of durvalumab prior to and during the COVID-19 pandemic. Clinical documentation was analysed from 216 consultations across 40 patients receiving 2-weekly durvalumab and 66 consultations of 14 patients who switched from 2-weekly to 4-weekly durvalumab during the COVID-19 pandemic. In patients receiving 2-weekly durvalumab, the rate of grade 3 and 4 toxicities was 15 % compared to 7% in patients receiving 4-weekly durvalumab. Pre-existing autoimmune disease was considered a risk factor for the development of grade 3 or 4 toxicities. We did not observe any difference in the rate of grade 1 and 2 toxicities between the two groups. Our findings support the use of 4-weekly durvalumab during the COVID-19 pandemic and beyond, obviating the need for 2-weekly face-to-face consultations and blood tests, relevant given the current pandemic and the need to re-structure cancer services to minimise patient hospital visits and exposure to SARS-CoV-2.

Real-world outcomes in thoracic cancer patients with severe Acute respiratory syndrome Coronavirus 2 (COVID-19): Single UK institution experience.

BACKGROUND: UK COVID-19 mortality rates are amongst the highest globally. Controversy exists on the vulnerability of thoracic cancer patients. We describe the characteristics and sequelae of patients with thoracic cancer treated at a UK cancer centre infected with COVID-19. METHODS: Patients undergoing care for thoracic cancer diagnosed with COVID-19 (RT-PCR/radiology/clinically) between March-June 2020 were included. Data were extracted from patient records. RESULTS: Thirty-two patients were included: 14 (43%) diagnosed by RT-PCR, 18 (57%) by radiology and/or convincing symptoms. 88% had advanced thoracic malignancies. Eleven of 14 (79%) patients diagnosed by RT-PCR and 12 of 18 (56%) patients diagnosed by radiology/clinically were hospitalised, of which four (29%) and 2 (11%) patients required high-dependency/intensive care respectively. Three (21%) patients diagnosed by RT-PCR and 2 (11%) patients diagnosed by radiology/clinically required non-invasive ventilation; none were intubated. Complications included pneumonia and sepsis (43% and 14% respectively in patients diagnosed by RT-PCR; 17% and 11% respectively in patients diagnosed by radiology/clinically). In patients receiving active cancer treatment, therapy was delayed/ceased in 10/12 (83%) and 7/11 (64%) patients diagnosed by RT-PCR and radiology/clinically respectively. Nine (28%) patients died; all were smokers. Median time from symptom onset to death was 7 days (range 3-37). CONCLUSIONS: The immediate morbidity from COVID-19 is high in thoracic cancer patients. Hospitalisation and treatment interruption rates were high. Improved risk-stratification models for UK cancer patients are urgently needed to guide safe cancer-care delivery without compromising efficacy.