Cutaneous Side Effects of Modern Targeted Therapy and Immunotherapy in Patients with Dermatological Malignancies
Round 1
Reviewer 1 Report
This paper is a nice summary of cutaneous toxicities related to ICI and targeted therapy from published papers.
-method section should provide more details about the number of papers obtained from the search, what time period included for the search, and how many reviewed, reason for papers not included. Flowchart can be helpful.
-Tables for the less common side effects would be helpful if the frequency of the toxicities were reported
-minor edits
Author Response
Thank you for your remarks. The requested addition concerning period included for research has now been added in the ‘’Materials and Methods Section (highlighted in yellow) and a Flowchart is also added (see Fig. 1).
As far as the frequency of less common side effects is concerned, this has not been documented in any study so far, and we did not want to present data merely based on case series and case reports.
Reviewer 2 Report
This is a comprehensive review of the cutaneous side effects of agents used to treat aggressive dermatologic malignancies, primarily melanoma. It is a comprehensive review and well written and organized.
The manuscript would benefit from figures depicting the more common dermatologic toxicities, as this would provide more practical appeal to the non-dermatologist readership.
There are many areas where the English usage is awkward and the paper can be substantially improved by assistance from a native English language speaker.
Author Response
Thank you for your remarks. Clinical figures of drug-associated skin toxicity have now been added (see Fig. 2, 3, 4 and 5).
The manuscript underwent proofreading for improvement of the used language.
Reviewer 3 Report
In this comprehensive review, the authors have addressed the cutaneous side effects and toxicities that are associated with the use of immunotherapy and targeted therapies, in the treatment of cutaneous malignancies.
1- In methods: is there any reason that sonidegib and relatlimab were not considered in the search? if not, they should be added to the searched papers.
2- page 3, paragraph 2: "spearing" should be changed to "sparing".
3- in the last paragraph of the introduction it is noted that "aim of this review is to provide summarized overview of the skin toxicities caused by aforementioned ICIs and targeted tumor therapies, in order to assist physicians in the prompt recognition and management" . However the body of the manuscript is mainly a description of each cutaneous reaction, and management has been left out. If management of skin toxicities is not the scope of the paper, this should be noted in the introduction.
4- if helping with establishing "prompt diagnosis" is the main focus of the paper: recommend providing a time to onset of immune-related cutaneous side effects such as noted in "Geisler et al, J Am Acad Dermatol, 2020".
- in the clinical context, how can a maculopapular rash secondary to other drugs ie morbilliform drug eruption be distinguished from the rash secondary to ICI?
5- recommend providing the CTCAE table for grading of dermatological toxicities.
6- recommend providing some figures for major groups of cutaneous toxicities.
several spelling errors noted; requires proofreading.
Author Response
- Thank you for your comment. Relatlimab and sonidegib are now also included in the review, accompanied by the corresponding literature (changes in text highlighted in light-blue)
- Error is now corrected
- Thank you for your comment. The following statement existed already in our manuscript, at the end of the ‘’Maculopapular rash’’ paragraph in the ICI section: ‘’ The detailed management of such manifestations is not the topic of this review therefore will not be further elaborated.’’
This statement has now been transferred to the Introduction, as you requested (changes in text highlighted in light-blue)
- Thank you for your remarks.
- We have already included a time of onset in the manuscript for all common cutaneous side effects (see text highlighted in light blue), except for the psoriasiform rash, pruritus and mucosal toxicity, as we did not find clear data in the literature concerning disease onset of the latter three adverse reactions.
- From a dermatological point of view, this question cannot be answered in a general ‘’one-fits-all’’ context and it should be assessed in a personalized manner, according to the individual patient we are dealing with.
- Thank you for your comment. A CTCAE table for grading of dermatological toxicities is now included in the manuscript.
- Thank you for your remarks. Four figures have now been included in the manuscript
Finally, the manuscript underwent proofreading for improvement of the used language.
Round 2
Reviewer 3 Report
na
na
