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.

Informations de copyright

Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Disclosure JDA reports research funding to the institution from Tesaro, outside the submitted work. ZB reports nonfinancial support from Bristol Myers Squibb and grants from Genentech/imCORE, outside the submitted work. BB reports research funding to the institution from Boehringer Ingelheim, Bicycle Therapeutics, Syros Pharmaceuticals, and Ikena Oncology, all outside the submitted work. TB-S reports research funding to the institution from Agios, Arys, Boston Biomedical, Bayer, Amgen, Merck, Celgene, Lilly, Ipsen, Clovis, Seattle Genetics, Array Biopharma, Genentech, Novartis, Mirati, Merus, AbGenomics, Incyte, Pfizer, BMS; consulting (to institution) for Ipsen, Array Biopharma, Pfizer, Seattle Genetics, Bayer, Genentech, Incyte, and Merck; consulting (to self) for AbbVie, Boehringer Ingelheim, Janssen, Eisai, Daiichi Sankyo, Natera, Treos Bio, Celularity, Exact Science, Sobi, BeiGene, Xilis, Astra Zeneca, and Foundation Medicine; serving on Independent Data Monitoring Committee/Data and Safety Monitoring Board (to self) for AstraZeneca, Exelixis, Lilly, PanCAN, and 1Globe; positions on Scientific Advisory Board for Imugene, Immuneering, and Sun Biopharma; and inventions/patents (WO/2018/183488 and WO/2019/055687), all outside the submitted work. SB reports being on advisory boards for Bristol Meyers Squibb and Seattle Genetics. MAB reports personal fees from Exelixis, Bristol-Myers Squibb, Bayer, Eisai, Pfizer, AstraZeneca, Janssen, Genomic Health, Nektar, and Sanofi; grants from Xencor, Bayer, Bristol-Myers Squibb, Genentech/Roche, Seattle Genetics, Incyte, Nektar, AstraZeneca, Tricon Pharmaceuticals, Peloton Therapeutics, and Pfizer, outside the submitted work. NB reports honoraria from Novartis, Pfizer, Roche, and Lilly, outside the submitted work. DWB reports research funding to the institution from Exelixis, Ayala, Merck, and Elevar, all outside the submitted work. DDC declares consulting or advisory role with Exelixis, outside the submitted work. TKC reports institutional and personal research support from Alexion, Analysis Group, AstraZeneca, Aveo, Bayer, Bristol Myers-Squibb/ER Squibb and sons LLC, Calithera, Cerulean, Corvus, Eisai, Exelixis, F. Hoffmann-La Roche, Foundation Medicine Inc., Genentech, GlaxoSmithKline, Ipsen, Lilly, Merck, Novartis, Peloton, Pfizer, Prometheus Labs, Roche, Roche Products Limited, Sanofi/Aventis, Takeda, Tracon; consulting/honoraria or advisory role with Alexion, Analysis Group, AstraZeneca, Aveo, Bayer, Bristol Myers-Squibb/ER Squibb and sons LLC, Cerulean, Corvus, Eisai, EMD Serono, Exelixis, Foundation Medicine Inc., Genentech, GlaxoSmithKline, Heron Therapeutics, Infinity Pharma, Ipsen, Jansen Oncology, IQVIA, Lilly, Merck, NCCN, Novartis, Peloton, Pfizer, Pionyr, Prometheus Labs, Roche, Sanofi/Aventis, Surface Oncology, Tempest, Up-to-Date; CME-related events (e.g. OncLive, PVI, MJH Life Sciences); stock ownership in Pionyr, Tempest; patents filed, royalties, or other intellectual properties related to biomarkers of immune checkpoint blockers; fees for travel, accommodations, expenses, medical writing in relation to consulting, advisory roles, or honoraria; and no speaker's bureau; also supported in part by the Dana-Farber/Harvard Cancer Center Kidney SPORE and Program, the Kohlberg Chair at Harvard Medical School and the Trust Family, Michael Brigham, and Loker Pinard Funds for Kidney Cancer Research at DFCI. DBD reports consulting for Ipsen, Boehringer Ingelheim; ASCO Young Investigator Award from Conquer Cancer Foundation, outside the submitted work. AE reports grant support from AstraZeneca, outside the submitted work. DF reports research funding to the institution from Viracor-Eurofins and Astellas, all outside the submitted work. LAF reports clinical trial funding to the institution from BMS, EMD Serono, Pfizer, Merck KGaA, Array, Kartos, Merck, and Incyte, ECOG-ACRIN study funding from Array; and personal fees from Elsevier and Via Oncology, outside the submitted work. DBF reports honoraria from Castle Biosciences. SMG reports Honoraria from AstraZeneca, Merck, Genentech/Roche; consulting or advisory role with Genentech/Roche, AstraZeneca, Bristol-Myers Squibb, Takeda, Xcovery, Boehringer Ingelheim, Novocure, Daiichi Sankyo, Novartis, Jazz Pharmaceuticals, Blueprint Medicines, Eli Lilly, Pfizer, Janssen Oncology; research funding (to self) from Merck, AstraZeneca; research funding (to institution) from Genentech/Roche, Merck, Blueprint Medicines, ARIAD/Takeda, Astellas Pharma, Lycera, Daiichi Sankyo, IMAB, Nektar, AstraZeneca, Pfizer, Amgen; travel, accommodations, expenses from Genentech/Roche, Merck; and other relationship from AstraZeneca, all outside the submitted work. MDG reports personal fees from Genentech, Pfizer, Astra Zeneca, Merck, Bristol Myers Squib, Dragonfly, Dracen, Seattle Genetics, and Astellas, outside the submitted work. 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TRH reports consulting or advisory role with Curium, ScioScientific, TERUMO, Lexicon, Ipsen, Advanced Accelerator; research funding from Ipsen, ArQule, Agios, Thermo Fisher Scientific, Basilea. BH reports research funding to the institution from Amgen, AbbVie, BI, Mirati, Merck, Eli-Lilly, AstraZeneca, BMS, Novartis, GSK, Pfizer, Advaxis, and Guardant Health; consulting/advisory role with Merck, BMS, Genentech, AstraZeneca, Amgen, Novartis, TPT, VI, Guardant Health; and honoraria from PER and OncLive, all outside the submitted work. JEH reports research funding from Regeneron and Dendreon; and travel, accommodations, and expenses from Genzyme. CH reports funding from the Henry Ford Cancer Institute supporting the current work; research funding to institution from Merck, Exelixis, Bayer, AstraZeneca, Genentech, Dendreon and Bausch; personal fees from Sanofi/Genzyme, Dendreon, Exelixis, Bristol Myers Squibb, Astellas, Medivation, Bayer, and Janssen Scientific, all outside the submitted work; and stock ownership by an immediate family member in Johnson and Johnson. DBJ reports advisory board participation for Array Biopharma, BMS, Catalyst Biopharma, Iovance, Jansen, Merck, Novartis, and OncoSec, and receives research funding from BMS and Incyte, all outside the submitted work. AK reports support to his institution from TESARO, Halozyme, Geistlich Pharma, Astellas Pharma, and Rafael Pharmaceuticals; and honoraria from OncLive, outside the submitted work. ARK (or an immediate family member) has currently or during the past 2 years owned stock or held an ownership interest in Merck, Sanofi, and BMS. VSK reports personal fees from Pfizer, Janssen, Dendreon, AstraZeneca, Seattle Genetics, and Clovis; grants (for institution) from Nektar, Novartis/Endocyte, Janssen, Clovis, and Prostate Cancer Foundation, all outside the submitted work. NMK reports personal fees from G1 Therapeutics, Invitae, Beyond Spring, Spectrum, BMS, Janssen, and Total Health, all outside the submitted work. PEL reports consulting/advisory role with Pfizer, Merck, Teva, BI, and Astra Zeneca, all outside the submitted work. AL-B reports personal fees from PSI CRO, Bayer, Blueprint, Astra-Zeneca, Medidata, Taiho, QED, Cardinal Health, BrightInsight, The Lynx Group, Boston Biomedical, Amgen, Bayer, Guardant, Natera, Eisai, Ipsen, and Merck; and stock options from Massive Bio, outside the submitted work. GdLL reports honoraria from Boehringer Ingelheim; consulting or advisory role for Pfizer and AstraZeneca; research funding from AstraZeneca; funding to his institution from Merck Sharp & Dohme, EMD Serono, AstraZeneca, Blueprint Medicines, Tesaro, Bavarian Nordic, NOVARTIS, G1 Therapeutics, Adaptimmune, BMS, GSK, AbbVie, Rgenix, Pfizer, Roche, Genentech, Lilly, and Janssen; travel, accommodations, and expenses from Boehringer Ingelheim, Pfizer, E.R. Squibb Sons, LLC, Janssen. GHL reports grants from AMGEN (institution); personal fees from G1 Therapeutics, TEVA, Samsung Bioepis, Beyond Spring, and Merck, outside the submitted work. RRM reports research funding from Bayer, Pfizer, Tempus; serves on Advisory Board for AstraZeneca, Bayer, Bristol Myers Squibb, Calithera, Exelixis, Janssen, Merck, Novartis, Pfizer, Sanofi, Tempus; is a consultant for Dendreon, Vividion; and serves on the molecular tumor board at Caris. RAM grants from Incyte, CTI, AbbVie, and Celgene; personal fees from Novartis, Genentech, Sierra Oncology, La Jolla, and Samus, outside the submitted work. VM has currently or during the past 2 years employment and stock or other ownership interest with Johnson & Johnson, all outside the submitted work. GN reports research funding to the institution from Novartis, all outside the submitted work. JN reports personal fees from AstraZeneca, Clovis Oncology; all outside the submitted work. CAP (or an immediate family member) has currently or during the past 2 years owned stock or held an ownership interest in Pfizer, Epizyme, Inovio, OPKO Health Inc, Roche. JMP reports grant from Dana-Farber/Harvard Cancer Center Breast SPORE Program, outside the submitted work. PP reports receiving payment for speakers' bureau from Novartis, Daichi Sankyo, Genentech, Seattle Genetics, and Pfizer, all outside the submitted work. NAP reports personal fees from Eli Lilly, Merck, BMS, Genentech, AstraZeneca, Inivata, and Regeneron, outside the submitted work. SP reports personal fees from AbbVie, Amgen, AstraZeneca, Bayer, Biocartis, Boehringer-Ingelheim, Bristol-Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly, F. Hoffmann-La Roche, Foundation Medicine, Illumina, Janssen, Merck Sharp and Dohme, Merck Serono, Merrimack, Novartis, Pharma Mar, Pfizer, Regeneron, Sanofi, Seattle Genetics and Takeda, AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Merck Sharp and Dohme, Novartis, Pfizer, and Takeda; nonfinancial support from Amgen, AstraZeneca, Boehringer-Ingelheim, Bristol-Meyers Squibb, Clovis, F. Hoffmann-La Roche, Illumina, Merck Sharp and Dohme, Merck Serono, Novartis, Pfizer, and Sanofi; and personal fees from BioInvent (all fees to institution), outside the submitted work. DYR reports consulting/advisory role with and coverage of travel/accommodation expenses by Castle Biosciences, all outside the submitted work. BIR reports grants, personal fees, and nonfinancial support from Merck; grants and personal fees from BMS, Pfizer, Aveo, and Genentech; grants from Astra Zeneca; personal fees from Synthorx, 3D Medicines, Aravive, Surface Oncology, and Arrowhead Therapeutics; and other from PTC Therapeutics, outside the submitted work. RPR reports research grants to her institution from BMS and Janssen and has worked as a consultant/advisor and received honoraria from BMS and Janssen, all of which are outside the scope of submitted work. ALS reports travel support provided by Pfizer and Astellas. GKS reports personal fees from Apexigen, Array, Epizyme, GenCirq, Daiichi Sankyo, Fortress, Iovance Biotherapeutics, Bayer Pharmaceuticals, Pfizer Oncology, Array Advisory Board, Oncogenuity, Puretech, PTC Therapeutics, Ellipses Pharma, Concarlo; advisory board for Bionaut; grants from Astex; stock ownership in Pfizer, all outside the submitted work. SS reports stock and other ownership interests in Grand Rounds, Janssen, and Natera. YS reports honoraria from Boehringer Ingelheim, AstraZeneca, Novartis, and Eisai; consulting or advisory role with Pfizer, AstraZeneca, Novartis, Roche, Genentech, and Janssen, all outside the submitted work. MAT reports travel support from Syapse, Royalties from UpToDate, Connect MDS/AML Registry in Celgene (now owned by BMS), Myeloma Registry in Takeda; stock ownership in Doximity; personal fees from VIA Oncology (now owned by Elsevier ClinicalPath), Adaptive Advisory Board, and GSK; he is the local PI for Clinical Trials in AbbVie, BMS, CRAB CTC, Denovo, Research Network, Eli Lilly, LynxBio, Strata Oncology, and TG Therapeutics, all outside the submitted work. AKV reports research funding to the institution from BMS, MedPacto, Prelude, iOnctura, and Janssen; honoraria from Acceleron and Novartis; consulting/advisory role with Stelexis and Janssen; stock or other ownership in Stelexis; and an immediate family member with employment/leadership with CereXis, all outside the submitted work. DCV reports honoraria and speakers' bureau fees from CSL Behring, Merck Canada, Novartis Canada, Takeda, and UCB Biosciences GmbH, and travel accommodations from CSL Behring, and Avir Pharma, all outside the submitted work. He is supported by the Fonds de la recherche en santé du Québec (FRQS) Clinician-Scientist Junior 2 program. JLW reports grants from the National Cancer Institute during the conduct of the study; personal fees from Westat and IBM Watson Health; and other from HemOnc.org LLC, outside the submitted work. TMW-D reports stock and other ownership interests in High Enroll; honoraria from Physicians' Education Resource; consulting or advisory roles with Shattuck Labs, Rakuten Medical, Exicure; research funding from Merck, AstraZeneca/MedImmune, Bristol-Myers Squibb, GlaxoSmithKline, Caris Life Sciences, GlaxoSmithKline; travel, accommodations, expenses from Merck, Bristol-Myers Squibb, Bexion, AstraZeneca/MedImmune, Caris Life Sciences, Lilly, and Tesaro, all outside the submitted work. EW-B reports work in a consultant/advisor role for Astellas and BMS; funding support from Pfizer Global Medical Grants; other for Exelixis; and an immediate family member with stock ownership in Immunomedics and Nektar, all outside the submitted work. TZ reports research funding (to Duke) from Pfizer, Janssen, Acerta, AbbVie, Novartis, Merrimack, OmniSeq, PGDx, Merck, Mirati, Astellas, and Regeneron; consulting/speaking role with Genentech Roche, Exelixis, Genomic Health, and Sanofi Aventis; and serves on the consulting/advisory board for AstraZeneca, Bayer, Pfizer, Foundation Medicine, Janssen, Amgen, BMS, Calithera, Dendreon, and MJH Associates; stock ownership/employment (spouse) from Capio Biosciences, Archimmune Therapeutics, and Nanorobotics. AYZ has currently or during the past 2 years owned stock or held an ownership interest in Gilead Sciences. LZ reports personal fees from MERCK, outside the submitted work. All others have declared no conflicts of interest.