Carfilzomib-Induced Thrombotic Microangiopathy Treated with Eculizumab: A Case Report and Rapid Literature Review

Round 1

Reviewer 1 Report

Overall, this is a clear, concise, and well-written manuscript. The introduction is relevant and theory based. Sufficient information about the previous study findings is presented for readers to follow the present study rationale and procedures. The methods are generally appropriate. Overall, the results are clear and compelling with a possible exception:

How do the authors exclude the possibility of hemolytic uremic syndrome (HUS)? According to their report, the patient had bacteremia.

Author Response

Dear reviewer, 

thank you for your comments, 

please see the attachment for our responses

Author Response File: Author Response.pdf

Reviewer 2 Report

This is an interesting case report with well documented clinical parameters and renal pathology which is rare in this thrombocytopenic condition. The review of reported similar cases of carfilzomib induced TMA treated with eculizumab is nice but there is the publication bias of only successful cases reporting preferential. 

In the methodology, it would have been more appropriate to include carfilzomib induced TMA not treated with eculizumab and compare the patients who received or not the complement blocker. This is a major concern for trying to assess eculizumab efficiency in drug induced TMA in retrospective case series.

This approach was done for instance in gemcitabine induced TMA litterature by Grall, Grange et al. BMC Nephrology 2021.

The authors should cite the paper of Yui et al. AJH 2016 as they report patients who recover from TMA only by drug discontinuation as they discuss the fact that in their patient description, the platelet count was already increasing significantly before eculizumab start.

For the reasons above, the conclusion should be less strong upon introducing eculizumab in this proteasome inhibitor induced TMA.

Author Response

Dear reviewer, 

thank you for your comments, 

please see the attachment for our responses

Author Response File: Author Response.pdf

Reviewer 3 Report

Comments for author File: Comments.pdf

Author Response

Dear reviewer, 

thank you for your comments, 

please see the attachment for our responses

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

It is suggested to add the methods used to exclude the HUS in the manuscript. 

Author Response

Dear reviewer, 

Please see the attachment, 

 

Best regards, 

Federica PALLOTTI

Author Response File: Author Response.pdf

Reviewer 2 Report

The authors have adressed the concerns I had written in my review. The manuscript has been improved.

Author Response

Dear reviewer, 

We would like to thank again for your comments and constructive advices, 

Best regards, 

Federica Pallotti

Reviewer 3 Report

Dear authors,

congratulations on your effort. You have substantially improved the quality of your manuscript.

Excellent work! 

Best regards,

Author Response

Dear reviewer, 

We want to thank you again for yours attentive comments and advices, 

This helped us to improve our work, 

Thank you again, 

 

Best regards, 

 

Federica Pallotti