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Favorable overall survival with imetelstat in relapsed/refractory myelofibrosis patients compared with real-world data

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Abstract

In the MYF2001 trial, treatment of Janus kinase (JAK) inhibitor-relapsed/refractory intermediate-2 or high-risk myelofibrosis (MF) with imetelstat 9.4 mg/kg every 3 weeks demonstrated encouraging median overall survival of 29.9 months. To provide historical context, external real-world data (RWD) were collected from a study of 96 patients who had discontinued ruxolitinib and were subsequently treated with best available therapy (BAT) at Moffitt Cancer Center. A closely matched cohort was identified using the MYF2001 eligibility criteria, including patients with MF who had discontinued ruxolitinib due to lack or loss of response. Overall survival was measured from time of JAK inhibitor discontinuation to death or censored at last follow-up. To improve comparability, propensity score weighting approaches using average treatment effect for overlap population (ATO) and stabilized inverse probability treatment weighting (sIPTW) were used for 10 critical baseline covariates. Fifty-seven patients treated with imetelstat 9.4 mg/kg from MYF2001 and 38 patients treated with BAT from RWD were analyzed with improved balanced baseline covariates after propensity score adjustment, showing significantly lower risk of death with imetelstat compared with BAT (hazard ratio: 0.35; p = 0.0019). With sIPTW, results were similar. Results of sensitivity analyses were consistent with the primary analysis. In conclusion, treatment with imetelstat was associated with longer overall survival compared to BAT (30 vs 12 months, respectively) in closely matched patients with MF after JAK inhibitor failure, warranting further evaluation of imetelstat in this poor-prognosis patient population.

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Deidentified clinical trial data that underlie the reported results can be requested by any qualified researchers who engage in rigorous, independent scientific research. Proposals for access must include a research proposal for Geron’s review and a Statistical Analysis Plan, and if approved, access will require the execution of a Data Sharing Agreement. Data requests can be submitted starting 3 months after publication for a period of 12 months after publication, with possible extensions considered. For more information on the process, or to submit a request, please contact info@geron.com.

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Acknowledgements

Editorial support for this publication was provided by Laurie Orloski, of InSeption Group, funded by Geron Corporation.

Funding

This work was supported by research funding from Janssen Research & Development LLC and Geron Corporation.

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Authors and Affiliations

  1. Moffitt Cancer Center, 12902 USF Magnolia Drive, CSB 7th Floor, Tampa, FL, 33612, USA

    Andrew T. Kuykendall & Rami Komrokji

  2. Geron Corporation, Menlo Park, CA, USA

    Libo Sun, Faye Feller, Aleksandra Rizo & Ying Wan

  3. Icahn School of Medicine at Mount Sinai, New York, NY, USA

    John Mascarenhas

  4. Hôpital Saint-Louis, Paris, France

    Jean-Jacques Kiladjian

  5. AOU Careggi, University of Florence, Florence, Italy

    Alessandro M. Vannucchi

  6. Janssen Research & Development, Raritan, NJ, USA

    Julia Wang, Qi Xia, Eugene Zhu & Jacqueline Bussolari

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  1. Andrew T. Kuykendall
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  2. Libo Sun
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  4. Jean-Jacques Kiladjian
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Contributions

A.T.K, R.S.K, Y.W., J.B., and L.S. designed the study. Y.W., L.S., Q.X., E.Z., and J.B. made the figures; all authors collaborated in writing and reviewing the paper and approved the final submitted version.

Corresponding author

Correspondence to Andrew T. Kuykendall.

Ethics declarations

Ethics approval

An independent ethics committee/institutional review board (IRB) had given full approval of the protocol, any amendments, and the informed consent forms for MYF2001. IRB approval was obtained for the collection, analysis, and sharing of real-world data.

Consent to participate

Written informed consent was received by each patient (or a legally acceptable representative) before performance of any study-related activity in MYF2001. Patients in the real-world cohort were not consented for this analysis, as the data were derived per retrospective chart review.

Conflict of interest

A.T.K.—research support: Prelude, Sierra Oncology, Protagonist; Speakers Bureau: Novartis, Blueprint; advisory boards/honoraria: Celgene/BMS, Abbvie, Pharmaessentia, Novartis, Blueprint, CTI Biopharma, Incyte; J.M.—research support: Incyte, Janssen, CTI Bio, PharmaEssentia, Novartis, Roche, Kartos, Promedior Merck; consultancy: Promedior, Prelude, Galecto, Incyte, Celgene, Kartos, Geron; J.-J.K.—advisory board: Novartis, AOP Orphan, BMS, AbbVie; A.M.V.—advisory board: Novartis, Abbvie, Celgene, Incyte, Blueprint; Fees (lectures): Novartis, Celgene, Takeda, CTI; Y.W., F.F., L.S., A.R.—employment/equity ownership: Geron Corporation; J.W., Q.X., E.Z., J.B.—employment/equity ownership: Janssen Research and Development; R.S.K.—Speakers Bureau: Celgene/BMS, JAZZ, Agios, Abbvie; advisory boards/honoraria: Celgene/BMS, JAZZ, Agios, Abbvie, Novartis.

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Kuykendall, A.T., Sun, L., Mascarenhas, J. et al. Favorable overall survival with imetelstat in relapsed/refractory myelofibrosis patients compared with real-world data. Ann Hematol 101, 139–146 (2022). https://doi.org/10.1007/s00277-021-04683-w

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  • DOI: https://doi.org/10.1007/s00277-021-04683-w

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