Clinical Factors Associated with Long-Term Survival in Metastatic Melanoma Treated with Anti-PD1 Alone or in Combination with Ipilimumab

Round 1

Reviewer 1 Report

This interesting paper looks at clinical factors that may predict long-term survival in patients with metastatic melanoma treated with immune checkpoint Inhibitors.

In general the paper is well written however there are times that abbreviations are used without defining them either in a list of abbreviations or in text proper. Is often later in the text that the abbreviation is made clear.

Example Line No. 89, “by quality of survival (TTF)” left me baffled as to how TTF relates to quality of survival. Later in the text we learn it refers to “time to treatment failure”

To reiterate it’s important to list abbreviations used in the paper and spell it out at least once in the text so that the reader knows exactly what they are discussing.

Line 101 has a typo - I presume this should be ICI and ICL (which for a while I thought it was a new undescribed abbreviation!).

Line 113 All analyses were conducted using R. huh? What is R?

Line 119 “318 patients were first line.” This is an incomplete sentence and was hard to interpret.

The basis of figure 1 is not clear. Based on the title of the figure it describes the overall survival for the total patient cohort and yet the paper is about those who survive less than one year versus those who survive greater than three years. Should there not be some type of comparison of these two groups?

The tables nicely describe their findings.

The length of the discussion is appropriate for their new findings.

The authors should be more explicit as to why there is an urgent need to identify predictors of patients who will maximally benefit from ICIs.  Eg Limited resources (manpower and financial constraints), directing patient predicted to be poor responders to clinical trials, etc.

Author Response

Dear Reviewer, 

Thank you for your thorough read of our manuscript. We appreciate your carefully detailed feedback, which we have reviewed and incorporated into the manuscript, which we believe have made our findings clearer and our message stronger. 

Please see the attachment below. Please refer to the tracked version of the manuscript, to which the our rebuttal letter corresponds to . 

Best wishes, 

Siddhartha Goutam

Author Response File: Author Response.doc

Reviewer 2 Report

This is a retrospective study where the authors used the regression models and the data from the Alberta Immunotherapy database to access the predictors of long-term survivors of more than 450 metastatic melanoma patients treated with Immune checkpoint inhibitors over ten years. This study is vital because checkpoint inhibitors show long-term benefits for the responders but not for non-responders; hence the robust predictors to predict the response and survival of metastatic melanoma patients for checkpoint inhibitors are valuable. The authors' analyses suggested four prognostic markers that could be used to predict the long-term survival of metastatic melanoma patients treated with checkpoint inhibitors (Breslow's depth, normal LDH, normal albumin, and M-stage). This is, of course, a retrospective study, and the validation of these results in other cohorts and, finally, in the prospective studies can open new avenues for treating metastatic melanoma. The study is very well executed. The inclusion and exclusion criteria are well explained, and the statistics are used appropriately. I am delighted that the authors tested many prognostic markers that may affect survival directly or indirectly.

Author Response

Dear Reviewer, 

Thank you for your thorough read of our manuscript. We appreciate your carefully detailed feedback.

Please see the attachment. Please refer to the tracked version of the manuscript, to which the our rebuttal letter corresponds to . 

Best wishes, 
Siddhartha Goutam

Author Response File: Author Response.doc

Reviewer 3 Report

The authors present a very interesting study of clinical factors associated with improved survival following the use of checkpoint inhibitors in patients with melanoma. I have made some comments/suggestions for improving the manuscript which is highlighted text in the attached pdf. 

Thank you again. 

Comments for author File: Comments.pdf

Author Response

Dear Reviewer, 

Thank you for your thorough read of our manuscript. We appreciate your carefully detailed feedback, which we have reviewed and incorporated into the manuscript, which we believe have made our findings clearer and our message stronger. 

Please see the attachment below. Please refer to the tracked version of the manuscript, to which the our rebuttal letter corresponds to . 

Best wishes, 
Siddhartha Goutam

Author Response File: Author Response.doc

Round 2

Reviewer 3 Report

Thank you for making the changes.