MDS/MPN Response Criteria Tied to Survival

Overall response rate and complete response, as measured by the 2006 myelodysplastic syndrome (MDS) response criteria and the 2015 MDS/myeloproliferative neoplasm (MPN) syndrome response criteria, correlate strongly with overall survival in patients with MDS/MPN, according to a systematic review and meta-analysis published in Blood Neoplasia.¹ The findings, drawn from 18 studies encompassing 1269 patients, represent the first pooled analysis to test whether existing response metrics actually track long-term outcomes in this disease space.

Under the umbrella of MDS and MPN, patients can present with everything from severe cytopenia to profound myeloproliferation, the authors explained. Previously, these patients would be folded into MDS trials and assessed using MDS response criteria that were not built to capture proliferative features. To address that gap, an international consortium proposed MDS/MPN–specific response criteria in 2015,² building on the modified International Working Group (IWG) 2006 MDS criteria.³ Both frameworks have since been used in clinical trials, but until now, the researchers say, the relationship between response and overall survival (OS) has not been systematically tested.

The present investigators searched PubMed, Embase, Web of Science, and Scopus through December 31, 2025. After removing duplicates and screening titles, abstracts, and full texts against PROSPERO-registered criteria, 18 studies met the inclusion criteria (12 retrospective; 6 prospective): documented clinical response in patients with MDS/MPN and reported its association with OS, leukemia-free survival (LFS), or progression-free survival (PFS). One study included all MDS/MPN subtypes, and the remaining evaluated chronic myelomonocytic leukemia (CMML). Pooled HRs were generated using a random-effects model.

What Response Metrics Predicted Survival?

Overall response rate (ORR) by 2006 MDS criteria, reported in 10 studies covering 665 patients, showed a strong association with OS (HR, 0.39; 95% CI, 0.28-0.54; P < .0001), although there was strong heterogeneity across studies (I² = 71.8%). ORR by 2015 MDS/MPN criteria, reported in 4 studies covering 309 patients, showed a comparable association (HR, 0.48; 95% CI, 0.33-0.70; P = .0001) but less heterogeneity (I² = 31.7%).

Complete response (CR) by the 2015 criteria, evaluated in 2 studies and 130 patients, was the strongest predictor of survival in the analysis (HR, 0.25; 95% CI, 0.12-0.53; P = .0002); no study using the 2006 criteria reported CR-specific outcomes. Other individual metrics reported in at least 2 studies and significantly linked to OS were clinical benefit by 2015 criteria (HR, 0.33; 95% CI, 0.13-0.86; P = .0028), hematologic improvement by 2006 criteria (HR, 0.68; 95% CI, 0.55-0.83; P = .0002), and erythroid response by 2006 criteria (HR, 0.25; 95% CI, 0.14-0.43; P < .0001). Despite indicating that CR by the 2015 criteria was “the strongest predictor of OS” in the cohort, they cautioned that the small sample size and the CR definition under the newer criteria are notably stringent.

Not every metric held up, however. ORR by 2006 criteria showed no significant association with LFS, and no study reported LFS outcomes using 2015 ORR. Also, symptom response and 16-week red blood cell transfusion independence could not be quantitatively pooled. Separately, a post hoc analysis of a randomized phase 3 trial in proliferative CMML found that effective cytoreduction—defined as a white blood cell count below 10 x 10⁹ cells/L and an absolute monocyte count below 1.0 x 10⁹ cells/L at 6 months—was tied to improved OS regardless of treatment arm.⁴ A study of measurable residual disease (MRD) by flow cytometry in CMML linked MRD status to LFS and OS.⁵

The Impact on Future Investigation

Previous research on the relationship between response criteria and survival found that CR by the IWG 2006 criteria functioned as a valid OS surrogate specifically in higher-risk MDS, with a median OS of 21 months for complete responders vs 8 to 14 months across other response categories.⁶ This new MDS/MPN–focused analysis extends that question, and the authors say the results will likely inform ongoing revisions to the MDS/MPN response criteria by IWG members.

They describe the 2015 MDS/MPN criteria as “a key step for drug development in this rare disease group,” while cautioning that further work is needed to understand how responses “can be used as survival surrogates in clinical trials, especially in the context of [the] evolving paradigm of classification, prognostication, and disease assessment across related myeloid neoplasms.” Overall, they write, the results “demonstrate a critical ongoing data gap and highlight the need for ongoing prospective investigation.”

References

1. Hunter AM, Ball S, Buckstein R, et al. Evaluating response criteria in myelodysplastic/myeloproliferative neoplasms: a systematic review and meta-analysis. Blood Neoplasia. 2026;3(3):100266. doi:10.1016/j.bneo.2026.100266
2. Savona MR, Malcovati L, Komrokji R, et al. An international consortium proposal of uniform response criteria for myelodysplastic/myeloproliferative neoplasms (MDS/MPN) in adults. Blood. 2015;125(12):1857-1865. doi:10.1182/blood-2014-10-607341
3. Cheson BD, Greenberg PL, Bennet JM, et al. Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia. Blood. 2006;108(2):419-425. doi:10.1182/blood-2005-10-4149
4. Savona MR, Odenike O, Roboz GJ, et al. Efficacy and safety of oral decitabine/cedazuridine in the chronic myelomonocytic leukaemia subpopulations from phase 2 and 3 studies. Br J Haematol. 2025;207(2):432-444. doi:10.1111/bjh.20203
5. Wang L, Chen R, Li L, Zhu L, Huang X, Ye X. Prognostic implication of early minimal residual disease evaluation in patients with chronic myelomonocytic leukemia. Am J Cancer Res. 2022;12(5):2216-2225.
6. Melillo G. Study finds IWG 2006 response criteria valid in patients with higher-risk MDS. AJMC. January 7, 2021. Accessed August 13, 2026. https://www.ajmc.com/view/study-finds-iwg-2006-response-criteria-valid-in-patients-with-higher-risk-mds