Prospective Clinical Trials to Advance the Study of Immune Checkpoint Inhibitor Toxicity

Round 1

Reviewer 1 Report

 

The review "Prospective Clinical Trials to Advance the Study of Immuno-therapy Toxicities" is well written. I have only a minor suggestion. Please make a table with all the relevant clinical trial details.

 

Author Response

Dear reviewer, 

We are very grateful for your supportive comments and we have updated the manuscript to include a table detailing the relevant clinical trials as suggested. 

With thanks,

Dr Cluxton, Prof Naidoo

Reviewer 2 Report

Authors present a very well written manuscript on toxicity from immune checkpoint inhibitors. Over than being well presented and useful as a comprehensive review on the mechanisms and the general management, the manuscript is presented in a key interpretation of open issues and how clinical trials can inform and improve the knowledge and management of immune related toxicities.

A table/figure reporting the major issues and corresponding trials would add value to this manuscript.

 

Author Response

Dear reviewer,

We are grateful for your supportive comments and we have updated the manuscript to include a table detailing the relevant clinical trials as suggested. 

With thanks

Dr Cluxton, Prof Naidoo

Reviewer 3 Report

The focus of this review is on management algorithms for toxicities related to ICI. In fact, the treatment of IrAEs, especially corticoid-resistant IrAEs, is a serious medical problem. Therefore, this review is relevant and of interest to a wide range of clinicians.

This review focuses on the treatment of immune-related adverse events (irAEs). The review is relevant because of the increasing use of immune checkpoint inhibitors (ICIs). The current treatment of irAEs is fairly comprehensively reviewed. The perspectives on this matter are also explained.  The conclusions are consistent with the evidence and arguments.

The references are appropriate. The MS contains no figures or tables. Summary figures and (or) tables could have improved the MS.

 

My comments and suggestion.

There are repetitions in the abbreviations (IrAEs) in lines 40 and 42. The MS should be carefully checked for text repetitions and for using abbreviations.

Section 2 entitled “Mechanisms of Immune-related Toxicity” does not disclose these mechanisms (T-cells, antibody, macrophages ....?).

Sections 4 (Clinical trials in IrAEs) and 5 (Trials to Optimize Treatment of irAEs) should be combined into one section, including the subsections ( Colitis ….).

It would be appropriate to conclude the MS with a “conclusions” section. 

Author Response

Dear reviewer, 

We are grateful for the supportive comments and we have updated our manuscript in the following ways in response to your comments:

1. We have included a table to detail / illustrate the relevant clinical trials
2. We have addressed reptition and abbreviations in the text
3. We have disclosed mechanisms in the mechanisms section of the ms
4. We have combines sections 4 and 5 as suggested

Again, we are very grateful for your comments, which through addressing same, we have improved the clarity and accessibility of the manuscript.

With thanks,

Dr Cluxton, Prof Naidoo

Reviewer 4 Report

In this review, the authors explored the toxicities of immune checkpoint inhibitors, specifically focusing on immune checkpoint inhibitors rather than other cell-based therapies. Overall, this study provides clear and straightforward information. However, I have several suggestions to further improve the quality and soundness of this study:

 

1. Title: The current title, "Immunotherapy Toxicities of Immune Checkpoint Inhibitors," is too broad and may encompass various forms of immunotherapy. I recommend narrowing it down to "Toxicities of Immune Checkpoint Inhibitors" to better align with the specific scope of this review.

 

2. Introduction: It would be beneficial to include a comprehensive table summarizing the current approved immune checkpoint inhibitors and their reported toxicities. This would provide readers with a clear overview of the agents discussed in the review, supported by relevant clinical trial citations.

 

3. Visual aids: I strongly suggest the authors include tables and figures to visually present key concepts and findings. For example, a table detailing the current agents and strategies used to mitigate toxicities, such as Corticosteroids, infliximab, and mycophenolate mofetil, would enhance the manuscript's clarity. It is also essential to discuss the mechanisms and limitations of these strategies.

 

4. Balancing toxicity reduction and antitumor reactivity: The manuscript should address the delicate balance between reducing immune checkpoint inhibitor-induced toxicity and preserving antitumor immune response. Exploring strategies or findings that address this balance would greatly enhance the relevance and completeness of the study.

 

5. Specificity in clinical trials: When discussing specific clinical trials, it is important to mention the immune checkpoint inhibitor products used, rather than solely referring to them as anti-PD1 or CTLA4 inhibitors. For instance, it would be more informative to specify the use of Pembrolizumab or Nivolumab.

Author Response

Dear reviewer,

We are grateful for your supportive comments regarding our submission and we have addressed your comments as detailed below:

1. The title is now more speicific
2. We have included a table detailing the relevent ICI agents and clinical trials
3. The ms now includes a paragraph on the complex balance between antitumour function and IrAE, including the reported effect of immunosuppression on treatment efficacy
4. We have specified the specific ICI where appropriate

 

Again we are grateful for your rigorous review of our manuscript and we have, in addressing your comments, improved the clarity and accessibility of our manuscript.

 

With thanks,

Dr Cluxton, Prof Naidoo

Round 2

Reviewer 4 Report

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