Real-World Experience with Ruxolitinib in Myeloproliferative Neoplasms: A Single-Center Study from Oman

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Authors report data from e-records form 28 patients treated with ruxolitinib for MPN at a single center in oman. Some point to be considered:

1-A follow-up of 3 months appears too short to adequately assess treatment response, as RR6 is conventionally evaluated after at least 6 months.

2-The study population is limited (n = 28), which significantly restricts the robustness and generalizability of the conclusions.

3-Spleen size assessment seems to have been based solely on clinical (manual) evaluation. In the absence of imaging-based or standardized measurements, spleen response cannot be objectively or reliably quantified.

4-Similarly, treatment response cannot be objectively calculated without standardized criteria  symptom assessment (TSS).

5-The causes of death should be clearly reported and discussed, as they are essential for the interpretation of survival outcomes.

6-The Discussion section should be substantially expanded by incorporating comparisons with larger real-world datasets already available in the literature.

Overall, the manuscript does not appear to provide novel insights beyond existing evidence. Moreover, neither Total Symptom Score (TSS) nor spleen response were objectively assessed, further limiting the interpretability of the results. In light of these limitations, beyond addressing the requested revisions, the final section of the manuscript should be more strongly oriented toward comparison with existing data and toward suggestions for implementation in clinical practice, rather than focusing primarily on the reported results. A letter could be a better objective.

Author Response

Dear Editor and Reviewers,

We would like to express our sincere gratitude for the time and effort you have invested in reviewing our manuscript entitled:

“Real-World Experience with Ruxolitinib in Myeloproliferative Neoplasms: A Single-Center Study from Oman”

We greatly appreciate the insightful and constructive comments provided, which have been invaluable in improving the clarity, scientific rigor, and overall quality of our work. We have carefully reviewed all comments and have revised the manuscript accordingly.

In response to the reviewers’ suggestions, we have:

• Thoroughly reviewed and updated references and in-text citations to ensure their relevance, accuracy, and compliance with the journal’s formatting requirements.
• Highlighted all changes within the revised manuscript in red font to facilitate review.

We believe that these revisions have significantly strengthened the manuscript and addressed the reviewers’ concerns comprehensively.

Below, we provide a detailed, point-by-point response to each reviewer comment.

 

Reviewer 1 Comments

Authors report data from e-records form 28 patients treated with ruxolitinib for MPN at a single center in Oman. Some point to be considered:

1-A follow-up of 3 months appears too short to adequately assess treatment response, as RR6 is conventionally evaluated after at least 6 months.

Response: We thank the reviewer for this important comment. While the original manuscript stated a minimum follow-up of 3 months as a pre-requisite criterion for inclusion consideration, all patients in the final cohort had a minimum follow-up of at least 6 months, with a median follow-up of 49.1 months (IQR 16.3–81.7). The actual follow-up range was 6.2-121.1 months.

We agree that a longer follow-up is necessary to adequately assess treatment response. Accordingly, we have revised the manuscript to specify a minimum follow-up of 6 months in both the Methods and eligibility criteria sections for clarity and alignment with standard practice. The follow-up range has also been added to the Results section.

2-The study population is limited (n = 28), which significantly restricts the robustness and generalizability of the conclusions.

Response: We thank the reviewer for this important comment. We agree that the relatively small sample size is a limitation and may affect the robustness and generalizability of the findings. This has now been explicitly acknowledged and discussed in the revised manuscript under the limitations section.

We would also like to highlight that myeloproliferative neoplasms are relatively rare disorders, and that we included all consecutive eligible MPN patients who were referred and received ruxolitinib at our tertiary care hospital during the study period (we further clarified that in Sample size calculation section). Notably, real-world studies from the literature—particularly single-center experiences—often involve relatively small patient cohorts outside large registries. For instance, a Portuguese real-world study included only 15 patients (Almeida A., Value in Health, 2016), while a Turkish single-center study in myelofibrosis included 57 patients (Arikan F., Blood Research, 2021). Moreover, a longitudinal real-world study evaluating long-term infections in patients with MPNS only included 36 patient (Blanco-Sánchez et al., 2025), In this context, and considering the population size in Oman, the sample size of our study is consistent with previously reported real-world experiences.

3-Spleen size assessment seems to have been based solely on clinical (manual) evaluation. In the absence of imaging-based or standardized measurements, spleen response cannot be objectively or reliably quantified.

Response: We thank the reviewer for this important comment. We agree that imaging-based spleen volume assessment provides a more objective and standardized evaluation of spleen response. However, due to the retrospective nature of the study, imaging data were not consistently available, and spleen size assessment relied on clinically documented measurements from physical examination.

We acknowledge that this approach may introduce variability and limit the precision of response assessment. This limitation has now been explicitly addressed under Strengths and Limitations sub-section. Nevertheless, it is important to note that clinical palpation of spleen size remains commonly used in routine practice and has been reported in several real-world studies where standardized imaging assessments are not systematically performed.

4-Similarly, treatment response cannot be objectively calculated without standardized criteria symptom assessment (TSS).

Response: We thank the reviewer for this valid comment. We agree that the absence of standardized symptom assessment limits the objectivity of treatment response evaluation. Due to the retrospective design of the study, symptom assessment was based on clinical history and physician documentation rather than a structured instrument.

We acknowledge that this may affect the precision and comparability of symptom response outcomes. This limitation has now been explicitly addressed in the Discussion section. Notably, published data suggest a moderate to strong correlation between clinical symptom assessment and MFSAF TSS scores, which may partially support the validity of our findings (doi:10.1007/s10238-025-01830-9).

5-The causes of death should be clearly reported and discussed, as they are essential for the interpretation of survival outcomes.

Response: We thank the reviewer for this important comment. We agree that reporting the causes of death is essential for appropriate interpretation of survival outcomes. Accordingly, we have revised the Results section to include the available details for both reported deaths.

6-The Discussion section should be substantially expanded by incorporating comparisons with larger real-world datasets already available in the literature.

Response: The Discussion section has been substantially expanded as advised. We have incorporated detailed, data-driven comparisons with multiple real-world studies across different settings to better contextualize our findings. Specifically, we added comparisons with a multicenter Korean study (n=123) (Jung et al., 2022), a Turkish real-world cohort (n=57) (Arikan et al., 2021), and a Portuguese single-center experience (Almeida et al., 2016), in addition to existing references. These studies were selected to provide both large and smaller real-world perspectives, enabling more balanced and relevant benchmarking of our results.

To further strengthen disease-specific comparisons, we also included a large (n=126) real-world study in polycythemia vera (Coltoff et al., 2020). Additionally, we strengthened the safety discussion by incorporating long-term real-world data in 36 patient (Blanco-Sánchez et al., 2025), highlighting the evolution of adverse events over time.

Overall, the manuscript does not appear to provide novel insights beyond existing evidence. Moreover, neither Total Symptom Score (TSS) nor spleen response were objectively assessed, further limiting the interpretability of the results. In light of these limitations, beyond addressing the requested revisions, the final section of the manuscript should be more strongly oriented toward comparison with existing data and toward suggestions for implementation in clinical practice, rather than focusing primarily on the reported results. A letter could be a better objective.

We thank the reviewer for this thoughtful and constructive comment. We acknowledge that the absence of standardized assessments such as TSS and imaging-based spleen evaluation represents a limitation and may affect the interpretability of certain outcomes. These points have now been explicitly addressed in the revised manuscript.

However, we respectfully believe that our study provides novel and clinically relevant insights. Real-world data on ruxolitinib use in myeloproliferative neoplasms remain limited in the Middle East, and to our knowledge, this is among the first studies reporting outcomes from Oman. Our findings offer valuable context-specific information on treatment patterns, tolerability, and clinical outcomes in routine practice, which may differ from controlled clinical trial settings.

In response to the reviewer’s suggestion, we have revised the Discussion section to more explicitly compare our findings with existing literature and to highlight their implications for clinical practice, particularly in resource-limited and real-world settings. We believe that these additions strengthen the manuscript and support its contribution as an original real-world study rather than a brief report or letter.

Reviewer 2 Report

Comments and Suggestions for Authors

General Comments
The manuscript reports on a cohort of 28 patients with myeloproliferative neoplasms (MPNs) treated with ruxolitinib (RUX). The study focuses on spleen size changes, symptomatic improvement, hematological responses, adverse events, and reasons for treatment discontinuation.

While the study provides valuable real-world evidence from Oman, several significant limitations must be addressed. Specifically, the single-center retrospective design, the small sample size (n=28), and the low statistical power (51%) compromise the study's ability to identify meaningful clinical differences, potentially leading tofalse-negative findings.

Major Revisions

1. Safety and Tolerability Discrepancy: The authors state that Ruxolitinib (RUX) was "generally well tolerated" (lines 383-384) and that most adverse events were "manageable through dose adjustment or temporary interruption" (line 396). However, this appears fundamentally contradictory to the reported treatment discontinuation rate of 39-40%. If nearly 4 out of 10 patients permanently ceased therapy, the treatment cannot be described as "well tolerated" without further qualification. The authors must reconcile these conflicting statements and provide information of why patients discontinued (e.g., toxicity vs. lack of efficacy).
2. Spleen Assessment Methodology: The authors rely on clinical palpation (BCM) for spleen assessment. Given its subjective nature and the lack of volumetric imaging (MRI/CT), this methodology must be explicitly listed as a study limitation. The authors should discuss how this subjectivity might impact the reliability of the reported efficacy data.
3. Statistical Representation: Given the small sample size (n=28), presenting results solely as percentages can be misleading, as each patient represents a significant portion of the total. I suggest reporting absolute values (e.g., n/N) alongside percentages throughout the manuscript to ensure a more accurate representation of the data.

Minor Issues

• Nomenclature: Genes involved in fusions should be written in italics and separated by double colons (e.g., BCR::ABL1).

Author Response

Dear Editor and Reviewers,

We would like to express our sincere gratitude for the time and effort you have invested in reviewing our manuscript entitled:

“Real-World Experience with Ruxolitinib in Myeloproliferative Neoplasms: A Single-Center Study from Oman”

We greatly appreciate the insightful and constructive comments provided, which have been invaluable in improving the clarity, scientific rigor, and overall quality of our work. We have carefully reviewed all comments and have revised the manuscript accordingly.

In response to the reviewers’ suggestions, we have:

• Thoroughly reviewed and updated references and in-text citations to ensure their relevance, accuracy, and compliance with the journal’s formatting requirements.
• Highlighted all changes within the revised manuscript in red font to facilitate review.

We believe that these revisions have significantly strengthened the manuscript and addressed the reviewers’ concerns comprehensively.

Below, we provide a detailed, point-by-point response to each reviewer comment.

Major Revisions

1. Safety and Tolerability Discrepancy: The authors state that Ruxolitinib (RUX) was "generally well tolerated" (lines 383-384) and that most adverse events were "manageable through dose adjustment or temporary interruption" (line 396). However, this appears fundamentally contradictory to the reported treatment discontinuation rate of 39-40%. If nearly 4 out of 10 patients permanently ceased therapy, the treatment cannot be described as "well tolerated" without further qualification. The authors must reconcile these conflicting statements and provide information of why patients discontinued (e.g., toxicity vs. lack of efficacy).

Response: We thank the reviewer for this important observation. We agree that the statement regarding tolerability requires clarification in light of the reported discontinuation rate. Upon further careful analysis, we found that 10 out of 28 patients discontinued treatment due to adverse drug reactions or death. Notably, only 3 patients discontinued therapy due to disease progression. Other causes of discontinuation included patient decision (1/28; 4%), and transition to hematopoietic stem cell transplantation (1/28; 4%). This has now been clarified in the revised Results section, including the addition of death, and other discontinuation causes.

          Importantly, among patients who discontinued treatment, the median duration of therapy prior to discontinuation was 35 months (IQR 21–88), indicating that many patients remained on treatment for a substantial period before discontinuation. This suggests that discontinuation did not predominantly occur early due to immediate intolerance, but rather after prolonged treatment exposure in several cases. This has now been added to the results section.

Additionally, we have revised the Discussion to provide a more nuanced interpretation of tolerability, avoiding overgeneralization of the term “well tolerated.”

1. Spleen Assessment Methodology: The authors rely on clinical palpation (BCM) for spleen assessment. Given its subjective nature and the lack of volumetric imaging (MRI/CT), this methodology must be explicitly listed as a study limitation. The authors should discuss how this subjectivity might impact the reliability of the reported efficacy data.

Response: We thank the reviewer for this important comment. We agree that clinical palpation of spleen size is inherently subjective and less precise than imaging-based volumetric assessment. Due to the retrospective nature of the study, standardized imaging (CT/MRI) data were not consistently available, and spleen size assessment relied on clinically documented measurements below the costal margin (BCM).

We acknowledge that this approach may introduce inter-observer variability and could affect the precision and reliability of the reported spleen response outcomes. This limitation has now been explicitly stated in the Discussion section, including its potential impact on efficacy interpretation. Nevertheless, it is important to note that similar approaches have been reported in real-world studies where standardized imaging assessments are not routinely available.

Statistical Representation: Given the small sample size (n=28), presenting results solely as percentages can be misleading, as each patient represents a significant portion of the total. I suggest reporting absolute values (e.g., n/N) alongside percentages throughout the manuscript to ensure a more accurate representation of the data.

Response: The absolute values have been added, where applicable, as for the majority of the paper this was already applied.

 

Minor Issues

• Nomenclature: Genes involved in fusions should be written in italics and separated by double colons (e.g., BCR::ABL1).

Response: The gene names have been changed as per the proper nomenclature. 

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

Although the authors have revised the manuscript in response to the reviewers’ comments, some important limitations persist, but they have been correctly addressed in the discussion.  

Reviewer 2 Report

Comments and Suggestions for Authors

The authors have adequately addressed all reviewers concerns. The manuscript can be accepted for publication