Treatment Resistance Risk in Patients with Newly Diagnosed Multiple Myeloma Is Associated with Blood Hypercoagulability: The ROADMAP-MM Study
, Despina Fotiou 3, Theodoros N. Sergentanis 3, Loula Papageorgiou 1,2, Jawed Fareed 4, Anna Falanga 5, Michèle Sabbah 2, Laurent Garderet 6, Evangelos Terpos 3, Ismail Elalamy 1,2,7, Patrick Van Dreden 1,8 and Meletios A. Dimopoulos 3Round 1
Reviewer 1 Report
Thank you for the opportunity to review the manuscript. The paper is well written and engaging. Interesting observations are made on risk of treatment resistance in relationship with blood biomarkers of hypercoagulability in patients with newly diagnosed multiple myeloma. The article is easy to read and understand. There are no English language issues. The results are well presented, the discussion is detailed and comprehensive, and the conclusions are realistic. The article has no relevant weaknesses.
Author Response
Dear Reviewer 1
Thank you very mach for the appreciation of our work
Kind regards
Grigoris Gerotziafas
Reviewer 2 Report
This paper by Grigoris T Gerotziafas describes the potential usefulness of biomarkers of hypercoagulability for the evaluation of risk for primary treatment resistance in patients with newly diagnosed multiple myeloma (MM). It is a well-written, needed, and useful manuscript. This does an excellent job demonstrating significant differences of biomarkers of hypercoagulability in responder and non-responder in MM. This work is a good reminder for MM researchers to pay attention to coagulation in MM patients.
Comments:
- What is the rationale and validity of using treatment response after three months of treatment as the primary endpoint?
- Please show progression-free survival in MM patients with responders and non-responders
- The authors reported that established biomarkers of MM, such as ISS and high-risk cytogenetics did not differ between responders and non-responders. What could be the reason for this?
Author Response
1. What is the rationale and validity of using treatment response after three months of treatment as the primary endpoint?
Thank you for your comment. We set the primary endpoin at 3 months because we wanted to sensorise the model for a rapid evaluation of the response to the treatment. This could offer the opportunity to elaborate rapid revision of the therapeutic strategy. This issue could be adressed in future studies. To respond to you comments we added the following sentense in the Discussion "The interval of 3 months allows a rapid evaluation of the response to the treatment which, in future studies could be used for prompt optimization of the antimyeloma therapy". (Page 10, end of the 1st paragraph)
2. Please show progression-free survival in MM patients with responders and non-responders
Since the primary end-point was set at 3 months after treatment initiation the calculation of the disease free survival could be inaccurate and the results could me misleading regarding the global management of the patients. For this reason we did not perform this analysis and we did not include these data in the article
3. The authors reported that established biomarkers of MM, such as ISS and high-risk cytogenetics did not differ between responders and non-responders. What could be the reason for this?
Thank you for your comment which helps to clarify in the text that the ISS stage and cytogenetics are prinicipally related with the survival rather than with the response to the treatment. Accordingly we added in the Discussion section the following sentence: "Nevertheless, it is important to underline that ISS stage and high-risk cytogenetics are mandatory for the survival rather than for the response to the treatment." (Page 13, end of the 2nd paragraph)
