PONE-D-22-18355Costs, effectiveness, and safety associated with Chimeric Antigen Receptor (CAR) T-cell therapy: results from a Comprehensive Cancer CenterPLOS ONE

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Reviewers' comments:

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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5. Review Comments to the Author

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Reviewer #1: The articles in very valuable for those working in the field of hematology and for centres considering the implementation of CAR-T cell therapy.

Most centres and health care facilities consider the CAR-T therapy acquisition cost as the only determinant factor. The current data illustrates the auxiliary costs associated with diagnostics, hospitalization and management of complications and highlights the actual cost as well as the results in real-world and not in the context of pre-planned clinical trials.

The article also compares the cost to the cost of the procedure in different European countries.

The stratification of cost per stage as displayed in table 5 and by activity in table 6 is also of great importance and is very illustrative

very few corrections need to be made namely, a few abbreviations need to be highlighted PMBL, lin2 162, NT, line 182..

Reviewer #2: This is a very well written manuscript on the cost-effectiveness of commercial CART-cells. The authors must be commended for their detailed analysis of their own practice and how nicely the manuscript is structured.

I only have a few minor comments:

1. Response rate: the authors may choose whether the denominator is 20 (all patients included) or 18 (all patients treated), but never 16 (patients evaluated). Imagine now that I have a trial and 10 patients are treated: 8 patients are never evaluated for response because they die early or experience disease progression and 2 patients are evaluated. Both patients respond to therapy. You would never say that the response rate is 100%, right?

2. The sentence starting on line 188: "Four hospitalizations..." is unclear.

3. Line 227: "progressed/diseased" or "progressed/deceased"?

4. I would prefer the term "ICANS" to "NT".

5. Please define high-dose and low-dose corticosteroids. By the way, is this distinction important?

Reviewer #3: The manuscript describes costs of CAR-T cell therapy in DLBCL third line at a Portuguese CCC centre. The medical costs were as high as 97%.

The manuscript does not address the cost -effectiveness of the treatment as there is no historical comparison to a standard third line therapy before CAR-T, and the novelty of the manuscript is moderate. It is, however well performed. I am not an expert on cost estimations, but the methods seem reasonable. The efficacy of the treatment is hard to evaluate with a very short median follow up of 4 months.

Minor comments:

1.As this is an intention-to-treat analysis, I would prefer to add the 4 patients excluded (two died due to disease progression before CAR-T, two died after CAR T due to toxicity or progression.

2. Cellof origin is given for twelve patients with 8 missing. I think it is better to have two missing as COO seldom is given for PMBCL or transformed lymhomas (3 + 3 patients).

3. Bridging therapy is given, but I could not find lymphodepletion (I asssume FC or Bendamustin or neither)

4. Minor language deficiencies can be fixed during editorial review.

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Reviewer #1: Yes: Hadi A. Goubran Messiha

Reviewer #2: Yes: Julio Delgado

Reviewer #3: No

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Costs, effectiveness, and safety associated with Chimeric Antigen Receptor (CAR) T-cell therapy: results from a Comprehensive Cancer Center

PONE-D-22-18355R1

Dear Dr. Monjardino,

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.

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Kind regards,

Yasunori Sato

Academic Editor

PLOS ONE

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