Toxicity Profile of Chimeric Antigen Receptor T-Cell and Bispecific Antibody Therapies in Multiple Myeloma: Pathogenesis, Prevention and Management
, Fauzia Ullah 2, Serhan Unlu 2, Najiullah Omar 2, Nerea Lopetegui-Lia 3, Marissa Duco 4, Faiz Anwer 3, Shahzad Raza 3 and Danai Dima 2,3Round 1
Reviewer 1 Report (Previous Reviewer 1)
The issues of this reviewer have been adequately addressed.
Reviewer 2 Report (Previous Reviewer 3)
The authors addressed all my comments adequatly.
This manuscript is a resubmission of an earlier submission. The following is a list of the peer review reports and author responses from that submission.
Round 1
Reviewer 1 Report
This review summarizes toxicities associated with available CAR-T and bispecific antibody treatment. The review is well written and easy to follow. No obvious misinformation is detectable to this reviewer. My comments include:
- The review would benefit from specific information on the dosing of steroids given to prevent CRS. The information becomes very vague in this regard (..."steroids"...). A Table summarizing available information would be helpful.
- There is no discussion on treatment at symptoms vs pre-emptive vs prophylactic use of Tocilizumab. Actually, Toculizumab treatment must be discussed more carefully: dosing - repetitions (fix vs on-demand).
- Is there a need to give steroids ahead of Toci administration ?
- No discussion of lab parameters (IL-6 ? others) to identify (early) CRS is found. Is there a need for lab parameters ?
- Elranatamab is not discussed
- specific side effects of Talquetamab (skin/nails and their management) may be listed, as well as the specific side effects of CART targeting GPRc5d.
Author Response
We would like to thank reviewer 1 for their comments, and we appreciate their valuable suggestions, which have helped us to improve the quality of our manuscript. All changes can be tracked in red in the revised document. In addition, please find our point-to-point responses to the comments of reviewer 1 below.
- The review would benefit from specific information on the dosing of steroids given to prevent CRS. The information becomes very vague in this regard (..."steroids"...). A Table summarizing available information would be helpful.
Answer: We would like to thank the reviewer for their comment. We have included the recommend dose on page 6 line 255.
- There is no discussion on treatment at symptoms vs pre-emptive vs prophylactic use of Tocilizumab. Actually, Tocilizumab treatment must be discussed more carefully: dosing - repetitions (fix vs on-demand).
Answer: We would like to thank the reviewer for their comment. We have added a paragraph regarding this remark (page 6, line 258-264). Details about the dosing and frequency of Tocilizumab are mentioned in detail in Table 1.
- Is there a need to give steroids ahead of Toci administration?
Answer: We thank the reviewer for these important suggestions. We have expanded the section on toci and have included more information on the abovementioned remark in section 3.5.
- No discussion of lab parameters (IL-6 ? others) to identify (early) CRS is found. Is there a need for lab parameters ?
Answer: We would like to thank the reviewer for pointing this out. We have added more details on lab parameters on page 4 lines 147-157.
- Elranatamab is not discussed
Answer: We would like to thank their reviewer for this comment. Available information on Elranatamab, mainly deriving from abstract/poster presentations in annual meetings, has been added in Table 3. We did not discuss this further due to the lack of peer-reviewed literature on elranatamab at this moment.
- specific side effects of Talquetamab (skin/nails and their management) may be listed, as well as the specific side effects of CART targeting GPRc5d.
Answer: We have elaborated on this in section 7.
Reviewer 2 Report
The recent introduction into medical practice of new immunotherapy methods for malignant hemopathies has brought, in addition to promising results, a constellation of adverse effects less common with classical treatments.
Immunotherapy with bispecific antibodies and CAR-T cells is now a therapeutic possibility in multiple myeloma.
This review presents a detailed analysis of the adverse reactions reported to date both in clinical trials and in real life in patients with multiple myeloma.
Considering the novelty of these therapies as well as the appearance of less familiar adverse effects in the classical therapy of patients with multiple myeloma, the present work is useful by increasing awareness, and presenting current data regarding the incidence, severity and management of these complications.
I recommend the publication in its current form.
Author Response
We would like to thank reviewer 2 for taking the time to review our manuscript and we really appreciate their kind comments.
Reviewer 3 Report
The review entitled: “Toxicity Profile of Novel Chimeric Antigen Receptor T-Cell Therapies and Bispecific Antibodies in Multiple Myeloma” (curroncol-2398752) by Mariam Markouli et al. aims to review effective strategies for prevention, monitoring and management of toxicities in MM patients with novel chimeric antigen receptor T-cell therapies and bispecific antibodies.
Albeit the review is well written, prepared and of special interest, comments should be addressed.
Comments:
1. The manuscript should be shortened and focus more on strategies for prevention, monitoring and management of toxicities as mentioned within the manuscript as their major aims, accordingly the title should be adapted.
2. Since the table 3 gives a good overview for the specific toxicities of different BsAb-regimen the authors should shorten this section within the manuscript and rather enlarge table 3 or add an additional table were appropriate.
Author Response
We would like to thank reviewer 3 for their time, and we appreciate their valuable suggestions. Their comments have been insightful throughout this editing process and have helped us improve the quality of our manuscript. All changes can be tracked in red in the revised document. In addition, please find our point-to-point responses to reviewer 3 below.
- The manuscript should be shortened and focus more on strategies for prevention, monitoring and management of toxicities as mentioned within the manuscript as their major aims, accordingly the title should be adapted.
Answer: We would like to thank their reviewer for this comment. We have tried to shorten the manuscript to the best of our ability and focus more on the abovementioned remarks. We also changed the title accordingly.
- Since the table 3 gives a good overview for the specific toxicities of different BsAb-regimen the authors should shorten this section within the manuscript and rather enlarge table 3 or add an additional table were appropriate.
Answer: We would like to thank the reviewer for this suggestion. We have removed some information from the text and have added it to table 3.
