Letter to the Editor Regarding “Impact of COVID-19 on Hematologic Cancer Patients: Insights From the Late Pandemic Phase”

Abstract

We read with interest the recent article by Caracciolo et al. [1] evaluating the outcomes of patients with hematologic cancers and COVID-19 during the late pandemic phase. While we appreciate the authors' effort to provide real-world data in this particularly vulnerable population, we believe that the study conclusions are significantly limited by the omission of a crucial determinant of clinical outcome: the impact of COVID-19 treatment strategies that were progressively implemented and recommended by the Italian Drug Agency.

Indeed, the authors presented a detailed analysis of demographics, malignancy type, vaccination status, and outcomes, but failed to account for the role of antiviral agents, monoclonal antibodies, corticosteroids, and other immunomodulatory therapies. These interventions, whether administered during the early phase of the infection or in the advanced disease, may substantially influence patient prognosis. The decision to not include such information represents a major limitation, as several studies clearly demonstrated that treatment availability and timing are critical determinants of survival and morbidity among patients with hematologic malignancies and SARS-CoV-2 infection.

In particular, several studies [2-4] have shown that early administration of antiviral and targeted therapies significantly improves clinical outcomes and reduces mortality in this high-risk population. Moreover, other investigations [5, 6], demonstrated the beneficial impact of antiviral agents, either alone or in combined regimens, in patients with severe immunosuppression and hematological cancers. Failing to consider treatment administration as key variables may have introduced substantial bias into the analysis, especially considering that 2022–2023 was a period characterized by wide availability of effective therapeutic agents, including remdesivir and nirmatrelvir/ritonavir [7]. Moreover, given the variable efficacy of certain treatments, particularly monoclonal antibodies against different SARS-CoV-2 variants, individual therapeutic strategies may have significantly influenced the outcomes assessed in this study and should therefore be explicitly reported.

Without stratification according to the possible COVID-19 treatment received, it is difficult to determine whether the observed mortality rates are attributable primarily to the underlying hematologic malignancies, to inadequate immune protection post-vaccination, or to differences in the therapeutic management. Furthermore, given that treatment approaches evolved substantially during the late pandemic phase, their exclusion represents an important methodological limitation that weakens the reliability of the conclusions. In particular, it would be misleading to attribute the decrease in mortality solely to a lower virulence of SARS-CoV-2. Such an interpretation could inadvertently lead both clinicians and patients to underestimate the importance of vaccinations and early therapeutic interventions, despite the persistent risk of adverse outcomes in severely immunocompromised individuals. Although SARS-CoV-2 is no longer the predominant cause of respiratory infections, it continues to pose a significant risk to hematological patients [8]. Therefore, when preventive strategies fail, the importance of rapid differential diagnosis and prompt initiation of effective treatment should not be underestimated.

In light of these considerations, we would encourage the authors to provide, in future analyzes, detailed information on the type, timing, and coverage of COVID-19 treatments administered within their cohort. Such data not only align their findings with previous evidence, including studies conducted in their own region [2], but would also provide a more accurate and clinically meaningful interpretation of outcomes in patients with hematologic cancer during the endemic phase of COVID-19.

Jon Salmanton-García: writing – review and editing, validation. Antonella Cingolani: writing – review and editing, validation. Maria Mazzitelli: writing – original draft, supervision, conceptualization. Pierluigi Del Vecchio: writing – review and editing, supervision, validation. Livio Pagano: writing – review and editing, validation. Carlo Torti: writing – review and editing, conceptualization, validation.

The authors declare no conflicts of interest.

The authors have nothing to report.