Measurable Residual Disease Assessment in Multiple Myeloma: How Deep Is Enough?
Round 1
Reviewer 1 Report
The authors provide a very written and comprehensive review article on minimal residual disease in multiple myeloma. Information regarding NGF and NGS is very well described and up to date. CTPC data is also accurate and up to date. Regarding MRD in the clinical setting the authors describe the deferent scenarios of how MRD can be applied. MRD as prognostic factor, how therapy can be adapted according to MRD, how to use the MRD result to intensify therapy, and how beneficial is to reach MRD negativity.
I only have a few minor comments:
Line 377 ff Regarding Mass Spec method the information is not so precise. They describe MALDI-TOF (The binding site) and LC-MS as clonotypic peptide methods, which is not true. Only LC-MS method is based on the identification of the clonotypic peptide which needs to be identified at diagnosis or at a time point where the patient has some tumor load. MALDI-TOF method detects intact protein and base line measurement is not mandatory.
Line 746 – 781 MRD in the context of new therapies: I think it is worth mentioning that patients continue to relapse from MRD negative states even after CAR T-cell therapy (see Da Via et al, Nature Medicine 2021).
I would suggest to the authors proof reading by a native speaker, there are some grammar mistakes, and also some typos to correct. Some sentences were also difficult to read.
Author Response
Please see the attachment.
Author Response File: 
Author Response.pdf
Reviewer 2 Report
In this review the Authors provided and excellent review on the MRD in multiple myeloma from various points of view, all very interesting. The manuscript is detailed, clear, well written and clarifies some questions on the role of this method in the current and future management of MM. The review is comprehensive in scope and would benefit from only little changes outlined below:
· line 756: CARTITUDE-1 updated data after a median follow-up of 18 months have been presented at the last 2021ASH Meeting (modify reference 164 that is “Martin T et al, ASH 2021, abstract 549”)
· line 769 KarMMa study: the reference 165 should be modified since KarMMa study results have been published in the NEJM in 2021
· line from 787 to 798: I think that discussion about quadruplets evaluated in the CASSIOPEIA, GRIFFIN or MASTER trials should be included in the previous chapters for example in that discussing FORTE and MANHATTAN trials (line 590) and in this section should be included a discussion about the high quality responses reported with other new immunotherapies as bispecific antibodies
· reference 41: the journal in which it was published is Annals Oncology
Author Response
Please see the attachment.
Author Response File: Author Response.pdf
