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Based on the authors' point-by-point response and after a careful review by reviewers and the editor, the manuscript is now accepted for publication. Congratulations.
The revised version fulfills the requirements of basic reporting. The authors have adequately addressed all the issues that had been raised. No further comments from my side.
The experimental design of the revised version is rigorous and satisfactory. The methods are described in sufficient detail.
The findings are meaningful, interesting and solid. The conclusions in the revised version are well stated.
In the revised version of the manuscript, the authors have adequately addressed all the issues that had been raised. No further comments from my side.
In the manuscript entitled ¨Comparison of Anti-PD-1/PD-L1-based Regimens in relapsed/refractory diffuse large B-cell lymphoma: a meta-analysis¨, " the authors report a meta-analysis to compare anti-PD1/PD-L1 treatment in R/R DLBCL.
Nevertheless, some issues need clarification before acceptance.
The limited number of assays analyzed is a limitation of this manuscript; nevertheless, the authors declare this limitation, and the manuscript highlights the need for more CART mono- or combinatory research in R/R DLBCL treatment.
Authors must include a point-by-point response to reviewers in the shortest time possible.
The major revision is based on the reviewers' suggestions that improve the final manuscript version.
In this study, Jiang et al perform a meta-analysis of anti-PD1/PD-L1 based regimens in the context of relapsed/refractory diffuse large B cell lymphoma (R/R DLBCL). Importantly, R/R DLBCL still represents a major unmet medical need, especially in patients who are not suitable candidates for CAR T-cells. By systematically exploring 32 records including 29 studies, the authors conclude that anti-PD1/PD-L1 monotherapy is not recommended for unselected R/R DLBCL, whereas combination regimens deserve to be further investigated. The manuscript is well designed and well written and provides clinically meaningful information. However, a few issues require further care for improvement.
The experimental design is appropriate but should be further improved as detaild below:
MAJOR ISSUES
1) In the Introduction (lines 72-74), the authors quote R-CHOP as the only first line regimen for DLBCL. Polatuzumab containing regimens are now also approved as first line treatment and should be metioned.
2) High grade large B cell lymphoma (HGLBCL) is now treated differently from DLBCL, not otherwise specified (NOS), at least in first line. The authors state that their analysis included DLBCL, NOS, thus implying that HGLBCL is not included (lines 120-121). However, in the exclusion criteria (lines 126-130), HGLBCL is not listed. The authors should explicitely clarify this issue.
The findings are of value and are clinically meaningful. However, their interpretation should be improved as outlined below. Also, the findings generate perspectives that must be mentioned in the Discussion, as indicated below.
MAJOR ISSUES
3) As a rationale for their study, the authors correctly state that CAR T-cell therapy is restricted by many factors in many geographic areas, thus preventing their current application as a treatment option for R/R DLBCL. This is very true and poses a major unmet medical need worldwide. At the same time, though, the results presented by the authors document that the combination of anti-PD1/PD-L1 with CAR T-cells provides the best PFS and OS benefit in their meta-analysis. In this context, the authors should reconcile, ideally in the Discussion, these two features, i.e. difficulty in CAR T-cell access and the fact that nevertheless anti-PD1/PD-L1 combination treatments is most effective when combined with CAR T-cells.
4) In the Discussion, the authors must acknowledge the molecular heterogeneity of DLBCL and include a paragraph, as a future perspective, stating that genomic characterization on the liquid biopsy combined with radiomics may help identify patients who are best candidates to combination treatments. The authors should refer to a very recent report documenting that ctDNA on the liquid biopsy combined with radiomics predict outcome in DLBCL and allows to identify early responders/non-responders (Dondolin et al. Integration of [18F]FDG-PET radiomics with liquid biopsy improves outcome prediction in newly diagnosed diffuse large B-cell lymphoma. Leukemia. 2025 Jul 8. doi: 10.1038/s41375-025-02688-2). This is very important in light of precision medicine applied also to R/R DLBCL.
**PeerJ Staff Note**: It is PeerJ policy that additional references suggested during the peer-review process should only be included if the authors agree that they are relevant and useful.
MINOR ISSUES
1) Throughout the text, a space is required between a word preceding a bracket and the bracket itself.
2) TME is not spelled out in the text.
The language is clear and unambiguous and professional. The references and sufficient background is provided. The structure of the article is professional. The manuscript is self-contained with relevant results to hypotheses.
This manuscript is a meta-analysis on to assess the efficacy and safety of PD-1/PD-L1 monoclonal antibody in r/r DLBCL. The research question is well defined and meaningful. Such findings will support further exploration of PD-1/PD-L1-mAb-based therapies.
The findings are meaningful. The underlying data have been provided together with the statistical processing methods. The conclusions are well stated.
It would be better is the authors could discuss more on the findings from this meta-analysis. For example, whether such findings are also valid in some other cancer types and the potential reasons.
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