Dear Dr. LeBlanc,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

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ACADEMIC EDITOR:

Overall the manuscript is well written and potentially of great interest to the audience; however, some minor issues have to be addressed, as suggested by the Reviewers. 

Please revise the manuscript according to all Reviewers' suggestions and comments, in order to make it suitable for publication. 

Of particular interest would be to stratify the population into 2 groups: transplant-eligible and non-eligible patients (in order to provide more reliable information on OS and PFS), and according to treatment regimen applied due to expected differences in efficacy and prognosis; moreover, include detailed information about how differences in definition of TTI are managed during the analysis. 

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Please submit your revised manuscript by Aug 03 2025 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org . When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

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We look forward to receiving your revised manuscript.

Kind regards,

Carmelo Caldarella, Ph.D., M.D.

Academic Editor

PLOS ONE

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When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

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2. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information.

3. Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Additional Editor Comments:

Dear Authors, I have read carefully and with interest your manuscript and evaluated Reviewers suggestions. Overall the manuscript is well written and potentially of great interest to the audience; however, some minor issues have to be addressed, as suggested by the Reviewers.

Please revise the manuscript according to all Reviewers' suggestions and comments, in order to make it suitable for publication.

Of particular interest would be to stratify the population into 2 groups: transplant-eligible and non-eligible patients (in order to provide more reliable information on OS and PFS), and according to treatment regimen applied due to expected differences in efficacy and prognosis; moreover, include detailed information about how differences in definition of TTI are managed during the analysis.

Best regards

Carmelo Caldarella, PhD MD

Editor

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

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2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses??>

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

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3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable??>

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

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4. Have the authors described where all data underlying the findings will be made available when the study is complete??>

The PLOS Data policy

Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

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Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

Reviewer #1: Thank you for the opportunity to review this protocol. While I am not an expert in scoping review methodology, the manuscript appears to be well-structured, clearly written, and methodologically sound. The authors provide a clear rationale for the study and outline their objectives and methods in accordance with standard guidance. The topic is relevant and timely, and the proposed approach seems appropriate to map the existing literature in this area. I do not have any major concerns at this time.

Reviewer #2: Given the well-documented differences in outcomes between transplant-eligible and non-eligible patients, I recommend stratifying the study population into at least two groups to evaluate overall survival (OS) and progression-free survival (PFS), or alternatively focusing the analysis on just one of these categories. Therapeutic efficacy is not uniform across all regimens. Although IMiDs have been part of treatment protocols since 1999, their combination with proteasome inhibitors (PIs) became common only later in clinical practice. More recently, the introduction of anti-CD38 monoclonal antibodies has further impacted OS and PFS. If feasible, the data should also be stratified by treatment regimen—for example: VTD, VRD, RD, VD, VMP vs daratumumab-based or other monoclonal antibody-based regimens vs others.

Reviewer #3: This manuscript presents a scoping review protocol that aims to explore the evidence on time to treatment initiation (TTI) in adults newly diagnosed with multiple myeloma. The review is structured according to Joanna Briggs Institute methodology and PRISMA-ScR standards, with the goal of mapping definitions, outcomes, and research gaps related to TTI. This is a commendable and much-needed effort that aligns well with current research and clinical priorities in MM. My comments are given below;

Major:

1. Please clarify how differences in definitions of TTI will be managed during analysis. Will you categorize or synthesize them descriptively?

2. Consider discussing how language restrictions will be handled if English translations are not available.

3. Expand on how you plan to address publication bias and the potential variability in study quality.

4. Include a brief discussion of the anticipated contribution of this scoping review to clinical practice guidelines or research agendas.

5. Provide further rationale for the year 2000 as the search cut-off, beyond the general availability of newer treatments.

Minor:

1. Edit the abstract for clarity—avoid phrases like 'surgery' for describing transplantation.

2. In the methods, consider explaining whether reviewers will be blinded during abstract screening.

3. There is a duplicated reference (LeBlanc 2022, R6-8) that should be consolidated.

4. Include the final version of your PRISMA-ScR checklist as an appendix.

5. Table 1 could benefit from improved formatting for clarity in separating concepts and terms.

Suggested References:

1. Khorana AA, et al. Time to initial cancer treatment in the United States and association with survival over time: An observational study. PLoS One. 2019;14(3):e0213209.

2. Cone EB, et al. Assessment of Time-to-Treatment Initiation and Survival in a Cohort of Patients With Common Cancers. JAMA Network Open. 2020;3(12):e2030072.

3. Friese CR, et al. Diagnostic delay and complications for older adults with multiple myeloma. Leuk Lymphoma. 2009;50(3):392-400.

4. Kariyawasan CC, et al. Multiple myeloma: causes and consequences of delay in diagnosis. QJM. 2007;100(10):635-40.

5. LeBlanc MR, et al. A cross-sectional observational study of health-related quality of life in adults with multiple myeloma. Support Care Cancer. 2022;30(6):5239-48.

6. Peters MDJ, et al. Best practice guidance and reporting items for the development of scoping review protocols. JBI Evid Synth. 2022;20(4):953-68.

7. Tricco AC, et al. PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and Explanation. Ann Intern Med. 2018;169(7):467-73.

Reviewer #4: A well-designed and purposeful article. Raising awareness of the available evidence on this topic, within the MM clinical and research community, will guide future research to address identified knowledge gaps.

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what does this mean? ). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy

Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

Reviewer #4: No

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Protocol for a scoping review of time to treatment in adults with newly diagnosed multiple myeloma.

PONE-D-25-22988R1

Dear Dr. LeBlanc,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager®  and clicking the ‘Update My Information' link at the top of the page. For questions related to billing, please contact billing support .

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Carmelo Caldarella, Ph.D., M.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Dear Authors, thank you for having addressed all the concerns raised by the Reviewers and for having rendered this manuscript more scientifically sound. The manuscript is now suitable for publication in this journal.

Best regards,

Carmelo Caldarella

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

Reviewer #1: Yes

**********

2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses??>

Reviewer #1: Yes

**********

3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable??>

Reviewer #1: Yes

**********

4. Have the authors described where all data underlying the findings will be made available when the study is complete??>

The PLOS Data policy

Reviewer #1: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #1: Yes

**********

Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

Reviewer #1: The revised manuscript shows significant improvement in both clarity and scientific content. I do not have any additional comments or suggestions at this time.

**********

what does this mean? ). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy

Reviewer #1: No

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