Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 3 de 3
Add filters

Document Type
Year range
HemaSphere ; 6:1985-1987, 2022.
Article in English | EMBASE | ID: covidwho-2032163


Background: Ibrutinib (IBR) is an oral covalent Bruton tyrosine kinase inhibitor (BTKi), licensed for treatment of relapsed or refractory mantle cell lymphoma (MCL). Under NHS interim Covid-19 agreements in England, IBR with or without rituximab (R) was approved for the frontline treatment for MCL patients (pts) as a safer alternative to conventional immunochemotherapy. Although recent phase 2 studies have reported high response rates in low-risk patients for this combination in the frontline setting, randomised phase 3 and real-world data are currently lacking. Aims: To describe the real-world response rates (overall response rate (ORR), complete response (CR) rate) and toxicity profile of IBR +/-R in adult patients with previously untreated MCL. Methods: Following institutional approval, adults commencing IBR +/-R for untreated MCL under interim Covid-19 arrangements were prospectively identified by contributing centres. Hospital records were interrogated for demographic, pathology, response, toxicity and survival data. ORR/CR were assessed per local investigator according to the Lugano criteria using CT and/or PET-CT. Results: Data were available for 66 pts (72.7% male, median age 71 years, range 41-89). Baseline demographic and clinical features are summarised in Table 1. 23/66 pts (34.8%) had high-risk disease (defined as presence of TP53 mutation/deletion, blastoid or pleomorphic variant MCL, or Ki67%/MiB-1 ≥30%). IBR starting dose was 560mg in 56/62 pts (90%) and was given with R in 22/64 pts (34%). At a median follow up of 8.7 months (m) (range 0-18.6), pts had received a median of 7 cycles of IBR. 19/60 pts (32%) required a dose reduction or delay in IBR treatment. New atrial fibrillation and grade ≥3 any-cause toxicity occurred in 3/59 pts (5.8%) and 8/57 (14.0%) respectively. For the whole population and high-risk pts only, ORR was 74.4% and 64.7% respectively (p=0.2379), with a median time to response of 3.8m, coinciding with the first response assessment scan. Seven pts (16.7%), of whom 2 had highrisk disease, attained CR at a median of 6.0m. ORR for pts receiving vs not receiving R were 84.2% and 66.7% respectively (p=0.1904). IBR was discontinued in 20/61 pts (32.8%) at a median time to discontinuation of 4.1m, due to progressive disease (PD, 19.7%), toxicity (4.9%), death (3.3%;1 pt each of Covid-19 and E. coli infection), pt choice (3.3%) and other unspecified reasons (1.6%). 15/66 pts (22.7%) overall and 7/23 (30.4%) with high-risk disease progressed on IBR at a median time to PD of 4.0m. No pts underwent autologous stem cell transplantation consolidation during the study period. 12/57 pts (21.1%) received second line treatment (R-chemotherapy n=7, Nordic MCL protocol n=2, VR-CAP n=2, pirtobrutinib n=1). Response to second line treatment was CR in 4/11 pts, PD in 7/11. Of the 2 Nordic-treated patients, 1 had CR after cycle 2 and 1 PD. Fourteen pts (21.2%) died during the follow up period, due to MCL (n=11), Covid-19 (n=2) and congestive cardiac failure (n=1). Overall survival was lower for patients with high-risk disease (HR 0.55, p=0.038). Image: Summary/Conclusion: In this real-world UK cohort of pts receiving first-line IBR +/-R for MCL, including older and high-risk pts, we report high ORR rates in a similar range to the phase II Geltamo IMCL-2015 study of combination IBR-R in an exclusively low-risk population. Documented CR rates were lower, possibly reflecting a low usage of rituximab in the Covid-19 pandemic as well as CT assessment of response. Treatment was generally well tolerated, with low rates of toxicityrelated treatment discontinuation. The study is ongoing.

Clinical Cancer Research ; 27(6 SUPPL 1), 2021.
Article in English | EMBASE | ID: covidwho-1816938


Introduction: Cancer patients have been considered a high-risk population in the COVID-19 pandemic. We previously investigated risk of COVID-19 death in COVID-19 positive cancer patients during a median follow-up of 134 days, and identified the following risk factors: male sex, age >60 years, Asian ethnicity, hematological cancer type, cancer diagnosis for >2.5 years, patients presenting with fever or dyspnea, and high levels of ferritin and C-reactive protein (CRP). Here, we further investigate which factors are associated with a COVID-19 related death within 7 days of diagnosis. Methods: Using data from Guy's Cancer Centre and one of its partner trusts (King's College Hospital), we included 306 cancer patients with a confirmed COVID-19 diagnosis (February 29th-July 31st 2020). 72 patients had a COVID-19 related death (24%) of whom 35 died within 7 days (50%). Cox proportional hazards regression was used to identify which factors were associated with a COVID-19 related death <7 days of diagnosis. Results: Of the 72 cancer patients who had a COVID-19 related death, the mean age was 72 years (Standard Deviation (SD) 14). A total of 53 (74%) patients were men. 37 (52%) had a hematological cancer type, 47 (65%) had stage IV cancer, and 42 (58%) had been diagnosed with cancer more than 24 months before COVID-19 related death. In the group of patients who died within 7 days of diagnosis (n= 35), mean age was 73 years (SD 13.96), 24 (68%) were men, 20 (57%) had a hematological cancer type, 26 (74%) had stage IV cancer, and 24 (68%) had been diagnosed with cancer >24 months before COVID-19 diagnosis. Factors associated with COVID-19 related death <7 days of diagnosis were: hematological cancer (Hazard Ratio (HR): 2.74 (95% Confidence Interval (CI): 1.21-6.22)), 2-5 yrs since cancer diagnosis (HR: 4.81 (95%CI: 1.47-15.69)), and >5 yrs since cancer diagnosis (HR: 4.41 (95%CI: 1.38-14.06)). Additionally, patients who presented with dyspnea had increased risk of COVID-19 related death <7 days compared to asymptomatic patients (HR: 5.25 (95%CI 2.14-12.89)). CRP levels in the third tercile (146-528 mg/L) as compared to the first were also associated with increased risk of an early death due to COVID-19. Conclusion: From all the factors identified in our previous COVID-19 related death analysis, only hematological cancer type, a longer-established cancer diagnosis (2-5 years and more than 5 years), dyspnea at time of diagnosis and high levels of CRP were indicative of an early COVID-19 related death (within 7 days of diagnosis) in cancer patients.

Clinical Cancer Research ; 27(6 SUPPL 1), 2021.
Article in English | EMBASE | ID: covidwho-1816911


Background: The Coronavirus disease 2019 (COVID-19) pandemic continues to have a significant impact on the treatment of cancer patients. Understanding the clinical course, potential risk factors for severe infection and excess mortality, is essential to improve patient outcomes. We previously presented preliminary results from 156 SARS-CoV-2 positive cancer patients from Guy's Cancer Center, which suggested that increased COVID-19 mortality was associated with a diagnosis of cancer for over 2 years, Asian ethnicity and being on palliative treatment. Herein, we present an updated analysis using data from Guy's Cancer Centre and a partner Hospital Trust (King's College Hospital), with an increased number of patients and an extended follow up. Methods: We performed an analysis of all cancer patients who had a positive RT-PCR nasal/throat swab for SARS-CoV-2 infection at our Centers between 29th February and 31st July 2020. Associations between patients' demographics, clinical characteristics, and laboratory investigations with COVID-19 severity and mortality, were assessed using Logistic regression and Cox proportional hazards models. Results: 306 SARS-CoV-2 positive cancer patients were included in the analysis with a median follow up of 134 days (IQR 32-156). 184 (60%) were male and 217 (71%) were aged over 60 (mean age: 66). The most common malignancies were haematological (38%) and urological-gynaecological (20%). 218 (71%) had mild/moderate COVID-19 and 88 (29%) had severe disease. The overall COVID-related mortality rate was 24%;19% in solid and 32% in haematological cancers. Male sex [OR: 1.84 (95%CI:1.08-3.13)], Asian ethnicity [3.86 (1.20-12.36)], haematological cancer type [2.16 (1.18-3.95)], being diagnosed with cancer for 2-5 years [3.74 (1.80-7.78)] or ≥5 years [3.06 (1.50-6.26)] and a ferritin > 1964 mcg/l [54.92 (5.90-511.33)] were all associated with a risk of developing severe COVID-19 disease. Similarly, male sex [HR:1.97 (95%CI:1.15-3.38)], Asian ethnicity [3.42 (1. 59-7.35)], haematological cancer type [2.03 (1.16-3.56)] as well as a cancer diagnosis for >2-5 years [2.81 (1.41-5.59)] or ≥5 years [2.13 (1.06-4.27)] and a ferritin > 1964 mcg/l [16.11 (3.81-68.17)] were associated with an increased risk of death from COVID-19. Age >60 [2.14 (1.15-3.98)] and a raised CRP [4.10 (1.66-10.10)] were also associated with COVID-19 death. An inverse relationship was observed between a raised albumin and COVID-19 related death [0.12 (0.03- 0.51)]. Performance status and treatment paradigm were not associated with COVID-19 severity or mortality. Conclusions: This study further substantiates the evidence for an increased risk of severe COVID-19 infection and mortality for male and Asian patients with cancer, and those with haematological malignancies or with a diagnosis of cancer for over 2 years. These risk factors should be taken into account when making clinical decisions for cancer patients during the pandemic.