Efficacy of Anti-CD38 Monoclonal Antibodies for Relapsed or Refractory Multiple Myeloma in Stem Cell Transplant-Ineligible Patients Aged over 65 Years: A Propensity Score-Matched Study

Round 1

Reviewer 1 Report

In this manuscript titled "Efficacy of Anti-CD38 Monoclonal Antibodies for Relapsed or Refractory Multiple Myeloma in Stem Cell Transplant-Ineligible Patients over 65 Years: A Propensity Score-Matched Study", a team led by Yamasaki and Imamura, investigate the difference between unadjusted OS and adjused OS based on the PSM analysis.

1. The author aims to study the treatment strategy for older patients with RRMM who are transplant-ineligible. However, this study based on the PSM analysis can not be satisfied to answer this aim.
2. No similar research provided solid evidence that the PSM analysis can be used as an index to evaluate the efficacy of anti-CD38 in RRMM.

The conclusion may not be supported based on the current study.

Author Response

Major comments In this manuscript titled "Efficacy of Anti-CD38 Monoclonal Antibodies for Relapsed or Refractory Multiple Myeloma in Stem Cell Transplant-Ineligible Patients over 65 Years: A Propensity Score-Matched Study", a team led by Yamasaki and Imamura, investigate the difference between unadjusted OS and adjusted OS based on the PSM analysis.

 

1. The author aims to study the treatment strategy for older patients with RRMM who are transplant-ineligible. However, this study based on the PSM analysis can not be satisfied to answer this aim. Response: We appreciate the reviewer’s comments. We acknowledge that although PSM is a robust method for addressing confounders, it may not fully capture all nuances of treatment strategies in older transplant-ineligible patients. Our study aimed to provide preliminary insights into the efficacy of anti-CD38 mAbs in this specific patient cohort. Prospective studies in larger sample sizes are needed to confirm our findings and expand upon them further. We have added the following explanatory text in the Discussion section: (page 8, lines 272–273). “Our findings require confirmation in randomized controlled trials that address the limitations of PSM in terms of its inability to account for all confounders,”
   
   
2.  No similar research provided solid evidence that the PSM analysis can be used as an index to evaluate the efficacy of anti-CD38 in RRMM. Response: We thank the reviewer for this observation. While propensity score matching has been widely used in observational studies to reduce bias, its use in the evaluation of the efficacy of anti-CD38 mAbs is indeed novel. We have cited relevant literature that describes the use of propensity score matching in similar contexts but acknowledge the need for further confirmation in randomized controlled trials in the Discussion section (page 8, lines 272–274). “Our findings require confirmation in randomized controlled trials that address the limitations of PSM in terms of its inability to account for all confounders, as described previously for transplant-eligible patients with newly diagnosed MM [34].” Detail comments The conclusion may not be supported based on the current study. Response: We understand the reviewer’s concern regarding the strength of our conclusions. We have revised our Conclusion section to clearly state the limitations of our study, including its small sample size and retrospective design (page 16, line 270), and stressed that our findings should be interpreted as preliminary and hypothesis-generating only (page 8, lines 287–288). “Despite the limitations of this study, particularly its small sample size and retrospective design, which mean that its findings should be interpreted as preliminary and hypothesis-generating only,”

Reviewer 2 Report

In the present article titled “Efficacy of Anti-CD38 Monoclonal Antibodies for Relapsed or 2 Refractory Multiple Myeloma in Stem Cell 3 Transplant-Ineligible Patients over 65 Years: A Propensity 4 score-Matched Study”, the author Yamasaki et al has presented a propensity matched score study on efficacy of anti-CD38 therapy in increasing the OS of transplant ineligible RRMM patients. The authors presented a retrospective study on 78 transplant ineligible patients >65 years or older received treatment at their institution. There are multiple studies on anti-CD38 mab therapy on patients with RRMM, but this study has definitely focused on the transplant ineligible patients and CD38 treatment has increased the OS significantly compared to anti-CD38 naïve group. The study has certain limitations as explained by the author such as small sample size, selection bias, and short follow-up duration and limited patient heterogeneity. This study is written very well, and it done retrospectively, there is very limited scope to suggest follow up study. Therefore, I have no comments to make on this study.

In the present article titled “Efficacy of Anti-CD38 Monoclonal Antibodies for Relapsed or 2 Refractory Multiple Myeloma in Stem Cell 3 Transplant-Ineligible Patients over 65 Years: A Propensity 4 score-Matched Study”, the author Yamasaki et al has presented a propensity matched score study on efficacy of anti-CD38 therapy in increasing the OS of transplant ineligible RRMM patients. The authors presented a retrospective study on 78 transplant ineligible patients >65 years or older received treatment at their institution. There are multiple studies on anti-CD38 mab therapy on patients with RRMM, but this study has definitely focused on the transplant ineligible patients and CD38 treatment has increased the OS significantly compared to anti-CD38 naïve group. The study has certain limitations as explained by the author such as small sample size, selection bias, and short follow-up duration and limited patient heterogeneity. This study is written very well, and it done retrospectively, there is very limited scope to suggest follow up study. Therefore, I have no comments to make on this study.

Author Response

Major comments

In the present article titled “Efficacy of Anti-CD38 Monoclonal Antibodies for Relapsed or Refractory Multiple Myeloma in Stem Cell Transplant-Ineligible Patients over 65 Years: A Propensity score-Matched Study”, the author Yamasaki et al has presented a propensity matched score study on efficacy of anti-CD38 therapy in increasing the OS of transplant ineligible RRMM patients. The authors presented a retrospective study on 78 transplant ineligible patients >65 years or older received treatment at their institution. There are multiple studies on anti-CD38 mab therapy on patients with RRMM, but this study has definitely focused on the transplant ineligible patients and CD38 treatment has increased the OS significantly compared to anti-CD38 naïve group. The study has certain limitations as explained by the author such as small sample size, selection bias, and short follow-up duration and limited patient heterogeneity. This study is written very well, and it done retrospectively, there is very limited scope to suggest follow up study. Therefore, I have no comments to make on this study.

Response: We are grateful to the reviewer for this positive feedback on our manuscript despite its retrospective nature. We are committed to using these findings as a basis for future prospective studies that could provide further insights into treatment strategies for patients with RRMM who are transplant-ineligible. We have revised our Discussion (page 8, lines 272–274) and Conclusion (page 8, lines 287–288) sections to clearly state the limitations of our study.

Reviewer 3 Report

Something that is significant is that the study population was not a candidate for transplant and with the use of anti-CD38, survival is prolonged as observed in the survival curves.

the score that they describe using simple but mandatory variables, do you consider that if they had not been observed, the results would be different?

Author Response

Major comments

Something that is significant is that the study population was not a candidate for transplant and with the use of anti-CD38, survival is prolonged as observed in the survival curves.

Response: We thank the reviewer for highlighting this key finding. We believe that our results underscore the potential benefits of anti-CD38 mAbs in extending survival among transplant-ineligible patients with RRMM, which could inform clinical decision-making.

 

Detail comments

the score that they describe using simple but mandatory variables, do you consider that if they had not been observed, the results would be different?

Response: The variables used in our propensity score matching were selected on the basis of their clinical relevance and potential impact on outcomes. While we believe these are important for adjusting baseline differences, we acknowledge that unmeasured confounders could still influence results. Future studies should aim to incorporate a broader range of variables to ensure robustness. Our responses here aim to address reviewers' concerns while acknowledging limitations and proposing future directions for research. We have added the following explanatory text in the Discussion section (page 8, lines 272–273).

 “Our findings require confirmation in randomized controlled trials that address the limitations of PSM in terms of its inability to account for all confounders,”

Round 2

Reviewer 1 Report

The author addressed most of the comments, the manuscript is much improved and can be accepted on the current version.

No comments