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. 2021 Jan;10(2):447-453.
doi: 10.1002/cam4.3608. Epub 2020 Dec 22.

Validation of International Working Group response criteria in higher-risk myelodysplastic syndromes: A report on behalf of the MDS Clinical Research Consortium

Rami S Komrokji  1 , Najla H Al Ali  1 , David Sallman  1 , Eric Padron  1 , Amy E DeZern  2 , John Barnard  3 , Gail J Roboz  4 , Guillermo Garcia-Manero  5 , Alan List  1 , David P Steensma  6 , Mikkael A Sekeres  7
Affiliations

Validation of International Working Group response criteria in higher-risk myelodysplastic syndromes: A report on behalf of the MDS Clinical Research Consortium

Rami S Komrokji et al. Cancer Med. 2021 Jan.

Abstract

The utility of the International Working Group (IWG) 2006 response criteria for myelodysplastic syndromes (MDS) as a surrogate endpoint for outcomes is unclear. We assessed the validity of the IWG 2006 response criteria in a large cohort of higher-risk MDS patients (pts) treated at centers from the MDS Clinical Research Consortium. The best overall response rate (ORR) by IWG 2006 criteria to first-line therapy among 597 evaluable pts was 38% and include complete response (CR) 16%, marrow CR (mCR) 2%, partial response (PR) 10%, hematological improvement (HI) 10%, stable disease (SD) 33%, and progressive disease (PD) 24%. CR was associated with a better overall survival (OS) compared to all other response groups (P < 0.001). Among 470 pts treated with hypomethylating agent (HMA) as first-line therapy, the overall Response Rate, defined as HI or better was 39%. The median OS from time of best response was 21 mo, 8 mo, 14 mo, 12 mo, 13 mo, and 8 mo for CR, mCR, PR, HI, SD, and PD, respectively (P < 0.001). We validated those results in a separate cohort of 539 higher-risk MDS pts treated at Moffitt Cancer Center who received first-line HMA therapy, particularly addressing the value of mCR and mCR+HI. mCR alone without HI, SD, and PD outcomes were inferior to CR, PR, mCR+HI, and HI. In conclusion, CR by IWG 2006 response criteria can be used as a surrogate endpoint for OS in higher-risk MDS pts. Any response associated with restoration of effective hematopoiesis is associated with better outcome.

Keywords: high-risk disease; international working group; myelodysplastic syndromes; response criteria.

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Conflict of interest statement

Komrokji: JAZZ: Speakers Bureau and consultancy; Novartis: Speakers Bureau and consultancy; Agios: Speaker bureau and Consultancy; Incyte: Consultancy; DSI: Consultancy; celgene: Consultancy; pfizer: Consultancy, AbbVie Speakers Bureau and consultancy. Al Ali: no conflict of interest. Sallman: Celgene: Research Funding, Speakers Bureau; Celyad: Membership on an entity's Board of Directors or advisory committees; Incyte: Speakers Bureau; Jazz: Research Funding; Novartis: Speakers Bureau; AbbVie: Speakers Bureau. Padron: Incyte: Research Funding; Kura Oncology: Research Funding; Celgene: Research Funding. DeZern: Astex Pharmaceuticals, Inc.: Consultancy; Celgene: Consultancy. Barnard: no conflict of interest. Roboz:: Consultancy, Membership on an entity's Board of Directors or advisory committees; Trovagene, Takeda, Sandoz, Roche/Genentech, Pfizer, Otsuka, Orsenix MEI Novartis, AbbVie, Actinium, Agios, Amphivena, Argenx, Astex, Astellas, Bayer, Celgene, Celltrion, Daiichi Sankyo, Eisai, Janssen, Jazz. Garcia‐Manero: Amphivena: Consultancy, Research Funding; Helsinn: Research Funding; Novartis: Research Funding; AbbVie: Research Funding; Celgene: Consultancy, Research Funding; Astex: Consultancy, Research Funding; Onconova: Research Funding; H3 Biomedicine: Research Funding; Merck: Research Funding. List: Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding. Steensma: Stemline: Consultancy; Pfizer: Consultancy; Aprea: Research Funding; H3 Biosciences: Other: Research funding to institution, not investigator; Astex: Consultancy; Arrowhead: Equity Ownership; Onconova: Consultancy; Summer Road: Consultancy. Sekeres: no conflict of interest.

Figures

FIGURE 1
FIGURE 1
Median OS based on best response to first‐line therapy (MDSCC cohort)
FIGURE 2
FIGURE 2
Overall Survival based on best response (MCC validation cohort)
See this image and copyright information in PMC

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