Outcome of early treatment of SARS‐CoV‐2 infection in patients with haematological disorders

Abstract

Outcome of early treatment of COVID-19 with antivirals or anti-spike monoclonal antibodies (MABs) in patients with haematological malignancies (HM) is unknown. A retrospective study of HM patients treated for mild/moderate COVID-19 between March 2021 and July 2022 was performed. The main composite end-point was treatment failure (severe COVID-19 or COVID-19-related death). We included 328 consecutive patients who received MABs (n = 120, 37%; sotrovimab, n = 73) or antivirals (n = 208, 63%; nirmatrelvir/ritonavir, n = 116) over a median of two days after symptoms started; 111 (33.8%) had non-Hodgkin lymphoma (NHL); 89 (27%) were transplant/CAR-T (chimaeric antigen receptor T-cell therapy) recipients. Most infections (n = 309, 94%) occurred during the Omicron period. Failure developed in 31 patients (9.5%). Its independent predictors were older age, fewer vaccine doses, and treatment with MABs. Rate of failure was lower in the Omicron versus the pre-Omicron period (7.8% versus 36.8%, p < 0.001). During the Omicron period, predictors of failure were age, fewer vaccine doses and diagnosis of acute myeloid leukaemia/myelodysplastic syndrome (AML/MDS). Independent predictors of longer viral shedding were age, comorbidities, hospital admission at diagnosis, NHL/CLL, treatment with MABs. COVID-19-associated mortality was 3.4% (n = 11). The mortality in those who developed severe COVID-19 after early treatment was 26% in the Omicron period. Patients with HM had a significant risk of failure of early treatment, even during the Omicron period, with high mortality rate.

Oral anti‐viral therapy for early COVID‐19 infection in patients with haematological malignancies: A multicentre prospective cohort

“…In a retrospective series by the Gruppo Italiano Malattie Ematologiche dell'Adulto (GIMEMA group), Marasco et al reported on 91 haematological patients treated with different types of neutralizing anti‐Spike MABs, finding an incidence of hospitalization for COVID‐19 of 12% and a mortality rate of 3.3% 6 . In the retrospective series by Mikulska et al, the incidence of lung failure was 5.8% for patients treated with anti‐virals (remdesivir or oral anti‐virals NIR/r and MOL) and 11.8% for MABs 15 . Evaluating patients' characteristics, the study of the GIMEMA group presented patients predominantly with active and recently treated HM, a prevalent diagnosis of lymphoma, and a comparable median age and prevalence of patients after transplantation or CAR‐T therapy to our cohort, while patients' comorbidities for this study were not described.…”

“…6 In the retrospective series by Mikulska et al, the incidence of lung failure was 5.8% for patients treated with anti-virals (remdesivir or oral anti-virals NIR/r and MOL) and 11.8% for MABs. 15 Evaluating patients' characteristics, the study of the GIMEMA group presented patients predominantly with active and recently treated HM, a prevalent diagnosis of lymphoma, and a comparable median age and prevalence of patients after transplantation or CAR-T therapy to our cohort, while patients' comorbidities for this study were not described. Compared to the cohort reported by Mikulska et al, although the median age, number of comorbidities and distribution of HMs were similar to that of our study, 66.5% had received anti-cancer treatment and 12.8% HSCT or CAR-T therapy within 12 months of COVID-19, while the remaining patients had been out of therapy for longer.…”

“…In response to the primary end-points of the study, COVID-19-related lung failure, defined as score 5 or more on the WHO clinical progression scale, 16 was reported in 19 Length of viral shedding, days (q1-q3) 12 (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22) patients (23.1%) of whom n. 9 (10.9%) in the NIR/r group and n. 10 (12.1%) in the MOL group (n.s). Specifically, n. 14 (17%) required low flux oxygen therapy or non-invasive ventilation, while n. 5 (6%) required admission to the intensive care unit (ICU) with invasive ventilation.…”

“…A recent retrospective multicentre study showed the outcome of early treatment with anti‐virals of mild/moderate COVID‐19 infection in patients with HM, underlining a high risk of failure of this approach especially in elderly patients. With the limit of the retrospective nature of the study, a comparison between anti‐virals (remdesivir, NIR/r or MOL) and MABs was proposed and an advantage for the anti‐viral therapy in terms of lung failure was shown (5.8% for anti‐virals and 11.8% for MABs in the Omicron infection period) 15 …”

“…With the limit of the retrospective nature of the study, a comparison between anti-virals (remdesivir, NIR/r or MOL) and MABs was proposed and an advantage for the anti-viral therapy in terms of lung failure was shown (5.8% for anti-virals and 11.8% for MABs in the Omicron infection period). 15 The purpose of this prospective cohort study, born from the close collaboration between Hematologists and Infectious diseases specialists, was to analyse the efficacy and safety of the oral anti-viral drugs NIR/r and MOL, associated or not with MABs, in outpatients diagnosed with HM presenting asymptomatic or paucisymptomatic early COVID-19 infection. The study hypothesis was to quickly offer an anti-viral treatment to a greater number of frail patients and regardless of the change of VOCs, and to identify predictors of severe infection.…”