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. 2020 Nov 2:12:1758835920968463.
doi: 10.1177/1758835920968463. eCollection 2020.

Symptomatic COVID-19 in advanced-cancer patients treated with immune-checkpoint inhibitors: prospective analysis from a multicentre observational trial by FICOG

Melissa Bersanelli  1 , Diana Giannarelli  2 , Ugo De Giorgi  3 , Sandro Pignata  4 , Massimo Di Maio  5 , Elena Verzoni  6 , Alberto Clemente  7 , Valentina Guadalupi  6 , Diego Signorelli  8 , Marcello Tiseo  9 , Raffaele Giusti  10 , Marco Filetti  11 , Marilena Di Napoli  4 , Lorenzo Calvetti  12 , Alessandro Cappetta  12 , Paola Ermacora  13 , Diego Zara  14 , Fausto Barbieri  15 , Cinzia Baldessari  15 , Vieri Scotti  16 , Francesca Mazzoni  17 , Antonello Veccia  18 , Pamela Francesca Guglielmini  19 , Marco Maruzzo  20 , Ernesto Rossi  21 , Francesco Grossi  22 , Chiara Casadei  23 , Alessio Cortellini  24 , Francesco Verderame  25 , Vincenzo Montesarchio  26 , Mimma Rizzo  27 , Manlio Mencoboni  28 , Fable Zustovich  29 , Lucia Fratino  30 , Saverio Cinieri  31 , Giorgia Negrini  32 , Maria Banzi  33 , Mariella Sorarù  34 , Paolo Andrea Zucali  35 , Gaetano Lacidogna  36 , Antonio Russo  37 , Nicola Battelli  38 , Giuseppe Fornarini  39 , Claudia Mucciarini  40 , Sergio Bracarda  41 , Andrea Bonetti  42 , Debora Pezzuolo  43 , Lucia Longo  44 , Donata Sartori  45 , Mauro Iannopollo  46 , Luigi Cavanna  47 , Fausto Meriggi  48 , Davide Tassinari  49 , Claudia Corbo  50 , Angela Gernone  51 , Veronica Prati  52 , Simona Carnio  53 , Pasqualina Giordano  54 , Angela Maria Dicorato  55 , Claudio Verusio  56 , Francesco Atzori  57 , Francesco Carrozza  58 , Stefania Gori  59 , Antonino Castro  60 , Sara Pilotto  61 , Vanja Vaccaro  62 , Elisabetta Garzoli  63 , Francesco Di Costanzo  17 , Evaristo Maiello  64 , Roberto Labianca  32 , Carmine Pinto  33 , Michele Tognetto  65 , Sebastiano Buti  66
Affiliations

Symptomatic COVID-19 in advanced-cancer patients treated with immune-checkpoint inhibitors: prospective analysis from a multicentre observational trial by FICOG

Melissa Bersanelli et al. Ther Adv Med Oncol. .

Abstract

Background: This prospective, multicentre, observational INVIDIa-2 study is investigating the clinical efficacy of influenza vaccination in advanced-cancer patients receiving immune-checkpoint inhibitors (ICIs), enrolled in 82 Italian centres, from October 2019 to January 2020. The primary endpoint was the incidence of influenza-like illness (ILI) until 30 April 2020. All the ILI episodes, laboratory tests, complications, hospitalizations and pneumonitis were recorded. Therefore, the study prospectively recorded all the COVID-19 ILI events.

Patients and methods: Patients were included in this non-prespecified COVID-19 analysis, if alive on 31 January 2020, when the Italian government declared the national emergency. The prevalence of confirmed COVID-19 cases was detected as ILI episode with laboratory confirmation of SARS-CoV-2. Cases with clinical-radiological diagnosis of COVID-19 (COVID-like ILIs), were also reported.

Results: Out of 1257 enrolled patients, 955 matched the inclusion criteria for this unplanned analysis. From 31 January to 30 April 2020, 66 patients had ILI: 9 of 955 cases were confirmed COVID-19 ILIs, with prevalence of 0.9% [95% confidence interval (CI): 0.3-2.4], a hospitalization rate of 100% and a mortality rate of 77.8%. Including 5 COVID-like ILIs, the overall COVID-19 prevalence was 1.5% (95% CI: 0.5-3.1), with 100% hospitalization and 64% mortality. The presence of elderly, males and comorbidities was significantly higher among patients vaccinated against influenza versus unvaccinated (p = 0.009, p < 0.0001, p < 0.0001). Overall COVID-19 prevalence was 1.2% for vaccinated (six of 482 cases, all confirmed) and 1.7% for unvaccinated (8 of 473, 3 confirmed COVID-19 and 5 COVID-like), p = 0.52. The difference remained non-significant, considering confirmed COVID-19 only (p = 0.33).

Conclusion: COVID-19 has a meaningful clinical impact on the cancer-patient population receiving ICIs, with high prevalence, hospitalization and an alarming mortality rate among symptomatic cases. Influenza vaccination does not protect from SARS-CoV-2 infection.

Keywords: COVID-19; SARS-CoV-2; cancer patients; immune-checkpoint inhibitors; influenza-like illness.

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Conflict of interest statement

Conflict of interest statement: The Federation of Italian Cooperative Oncology Groups (FICOG) received funding for the present study by Seqirus and Roche S.p.A.; the Federation also received funding during the conduct of the present study by Astra Zeneca, Bristol Myers Squibb (BMS), Sanofi. Melissa Bersanelli received funding for the present study by Seqirus and Roche S.p.A. (FICOG as Institution, no personal fees). She also received, outside the present work, research funding from Pfizer and Novartis (Institution), honoraria as speaker at scientific events (personal fees) by Astra Zeneca, Bristol Myers Squibb (BMS), Novartis and Pfizer; as consultant for advisory role (personal fees) by Novartis, BMS and Pfizer. Ugo De Giorgi received honoraria from AstraZeneca, Roche, MSD, Pfizer, GSK, Clovis, Incyte and research funding from Roche, AstraZeneca, MSD, Pfizer. Dr Di Maio reports personal fees from Bristol Myers Squibb, personal fees from Merck Sharp & Dohme, personal fees from AstraZeneca, personal fees from Janssen, personal fees from Astellas, personal fees from Pfizer, personal fees from Eisai, personal fees from Takeda, grants from Tesaro GSK, outside the submitted work. Sebastiano Buti received honoraria as speaker at scientific events and advisory role by BMS, Pfizer; MSD, Ipsen, Roche S.p.A., Eli Lilly, AstraZeneca and Novartis; he also received research funding from Novartis. Marcello Tiseo received honoraria (personal fees) by MSD, BMS, Boehringer (BI), Takeda, AstraZeneca, and research funding by AstraZeneca (Institution). Vieri Scotti participated, with personal fees, to advisory boards and speaker’s bureaus for Roche S.p.A. Dr Cortellini reports grants from AstraZeneca, grants from MSD, grants from BMS, grants from Roche, during the conduct of the study; grants from AstraZeneca, grants from MSD, grants from BMS, grants from Roche, grants from Novartis, outside the submitted work. Saverio Cinieri declared international board for Eli Lilly international. Paolo Andrea Zucali acts in a consultant or advisory role for Sanofi, BMS, Pfizer, MSD, Astellas, Janssen, Ipsen, Novartis, all outside the scope of work. Sergio Bracarda declares to have acted as advisory board member (uncompensated) for: Janssen, Astellas, Pfizer, MSD, BMS, Merck, AstraZeneca, AAA, Ipsen, Bayer, Roche/Genentech. Francesco Carozza declared personal fees from Janssen. Sara Pilotto reports personal fees from AstraZeneca, Eli Lilly, Boehringer Ingelheim, Merk & Co, Roche, outside the submitted work. All remaining authors have declared no conflicts of interest.

Figures

Figure 1.
Figure 1.
Pie graph representing the distribution of patients developing influenza-like illness (ILI) after 31 January 2020. COVID-19, infection by the SARS-CoV-2 virus.
Figure 2.
Figure 2.
Kaplan–Meier survival curves for patients with confirmed COVID-19 influenza-like illness (ILI) and patients with non-COVID ILI. (a) Kaplan–Meier survival curves for patients with confirmed COVID-19 ILI and patients with non-COVID ILI (calculated from the onset of influenza-like symptoms to death or to the last follow up for patients surviving to ILI); (b) Kaplan–Meier survival curve for patients with COVID-like ILI, compared with that of patients with confirmed COVID-19 ILI and with non-COVID ILI. COVID-19, infection by the SARS-CoV-2 virus. The blue line is for non-COVID-ILI and the green for COVID-19 ILI in (a) and (b), and the red line is for COVID-like ILI in (b).
Figure 3.
Figure 3.
Spider plot representing the trend of the lymphocyte count in patients with confirmed COVID-19 or COVID-like ILI at three timepoints. T0: start of immunotherapy with immune-checkpoint inhibitors; T1: during therapy; T2: close to COVID-19 diagnosis (immediately before or at hospital admission). The downward trend from T0 to T2 was statistically significant (p =  0.035). COVID-19, infection by the SARS-CoV-2 virus.
See this image and copyright information in PMC

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