Evaluating the Efficacy of Immunotherapy in Fragile Hospitalized Patients

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The study is interesting a well written. Focusing on frail patients, authors observed that immunotherapy may have a role in patients with good PS, fit to receive multiple cycles of IO, and normal LDH levels.

Major comment:

The definition of a ‘fragile patient with high likelihood of impaired immunity ‘ is, however, unclear in the paper. Patients with ECOG 0 or minor weight loss have been included. Authors should clearly define the fragile status of patients

 

Author Response

We thank the reviewers for their constructive comments on this manuscript. We are pleased to see that both reviewers agree this manuscript fills a gap in the literature and significantly contributes to our understanding of the efficacy of immunotherapy in a fragile patient population.

1. Please find attached the graphical abstract as recommended by the editor-in-chief.
2. Reviewer 1’s comment: “The definition of a ‘fragile patient with high likelihood of impaired immunity is, however, unclear in the paper. Patients with ECOG 0 or minor weight loss have been included. Authors should clearly define the fragile status of patients.”

In response to this comment, we have provided clarification in lines 90–91. In our study, the term “fragile patient with a high likelihood of impaired immunity” refers to patients who were either hospitalized or had been hospitalized within three months prior to receiving immunotherapy. The impaired immunity and fragile status of these patients have been documented in previous studies, as referenced in the introduction.

However, we also examined multiple variables within this group, including performance status (ECOG 0 or higher) and anthropometric parameters like weight loss (minor or major). These variables were analyzed to identify potential subsets of patients who, despite being considered fragile with impaired immunity, may still benefit from ICI treatment due to other favorable factors.

This explanation has now been added and highlighted in the manuscript. We appreciate your feedback in helping us improve the clarity of this manuscript.

Thank you for your continued guidance in refining our work.

Sincerely,
Dr. Charles Vincent Rajadurai - MDCM, PHD
Medical Oncologist

Reviewer 2 Report

Comments and Suggestions for Authors

This manuscript evaluates the efficacy of immunotherapy in fragile hospitalized patients. The study describes the results of a retrospective study who started immunotherapy (Checkpoint inhibitors) during hospitalization or within 3 months after. The study is of high interest because it analyses real life therapy data in contrast to controlled clinical studies with more stringent inclusion criteria, excluding in particular patients with too unfavourable parameters, such as worse performance status. The authors evaluate efficacy parameter, such as overall survival, progression-free survival, and objective response as well as the immune therapy induced adverse events (irAE), together with biomarkers and patient status data. The study shows a expected high percentage of therapy-related adverse events (in the range as expected), however, a lower response rate compared to controlled studies, indicating a bad efficacy-to-irAE ratio in fragile patients. This poor ratio is driven largely by patient parameters such as performance status, stage of disease, weight loss, neutrophil to lymphocyte ratio, low albumin, and high LDH. The disturbed efficacy to AE ratio can be counterbalanced by selecting patients with favourable biomarkers, better performance status and higher number of cycles of immune therapy. The study is well described, the data clearly presented, and the conclusions are adequate to the data. Overall, this study presents high scientific and medical interest and can be recommended for publication

Author Response

We thank the reviewers for their constructive comments on this manuscript. We are pleased to see that both reviewers agree this manuscript fills a gap in the literature and significantly contributes to our understanding of the efficacy of immunotherapy in a fragile patient population.

Please find attached the graphical abstract as recommended by the editor-in-chief. Thank you once again for your valuable feedback in helping us improve the clarity of this manuscript. We appreciate your continued guidance in refining our work.

Sincerely,
Dr. Charles Vincent Rajadurai - MDCM, PHD
Medical Oncologist

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

I have no further comments