Abstract
Introduction
Patients with relapsed/refractory Hodgkin lymphoma (R/R HL) experience high response rates upon anti-PD1 therapy. In these patients, the optimal duration of treatment and the risk of relapse after anti-PD1 discontinuation are unknown.
Methods
We retrospectively analyzed patients with R/R HL who responded to anti-PD1 monotherapy and discontinued the treatment either because of unacceptable toxicity or prolonged remission. A machine learning algorithm based on 17 candidate variables was trained and validated to predict progression-free survival (PFS) landmarked at the time of discontinuation of anti-PD1 therapy.
Results
Forty patients from 14 centers were randomly assigned to training (n = 25) and validation (n = 15) sets. At the time of anti-PD1 discontinuation, patients had received treatment for a median duration of 11.2 (range, 0—time to best response was not statistically significant in discriminating patients with PFS lesser or greater than 12 months). Considering PFS status as a binary variable (alive or dead) at a specific time point (12 months) is convenient, intuitive and allows for comparing the value of potential predicting variables in these two groups of patients. Nonetheless, this approach has two drawbacks: first, it binarizes outcome; second, it excludes patients alive with a time to last follow up lesser 12 months. Therefore, it is less powerful to demonstrate statistically significant association with PFS even if it exists 5 months. Patients discontinued anti-PD1 treatment either because of prolonged remission (N = 27, 67.5%) or unacceptable toxicity (N = 13, 32.5%). Most patients were in CR (N = 35, 87.5%) at the time of anti-PD1 discontinuation. In the training set, the machine learning algorithm identified that the most important variables to predict PFS were patients’ age, time to best response, and presence or absence of CR. The performance observed in the training set was validated in the validation set.
Conclusion
In this pilot, proof of concept study using a machine learning algorithm, we identified biomarkers capable of predicting the risk of relapse after anti-PD1 discontinuation (age, time to best response, quality of response). Once confirmed, these simple biomarkers will represent useful tools to guide the management of these patients.
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Change history
20 March 2021
A Correction to this paper has been published: https://doi.org/10.1007/s00259-021-05321-3
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Acknowledgments
We thank all the LYSA investigators and the LYSARC for their help in managing the study.
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G.M., L.D., and R.H. designed the research, analyzed data, and wrote the paper. P.B., C.H., M.G.S., K.B., B.D-F, J.B., J-M.S., E.N-V., M.M., H.G., A.S., C.A., C.C-S., M.D.R., and F.P. provided the data, and all authors reviewed and approved the final draft. This study was supported in part by Grant No. 20575 (to C.C-S) from the Italian Association for Cancer Research, Milan, Italy.
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G.M. and P.B. have received consulting fees and/or honoraria from Bristol-Myers Squibb. M.G.S received research grant form Gilead Sciences, and was consultant for Abbvie, Gilead Sciences, Janssen Cilag, Roche. E.N-V. received consulting fees from Sanofi. A.S. has received consulting fees from Takeda and Celgene. C.C.-S. received honoraria for speaker engagements from Bristol Myers Squibb, Merck Sharp & Dohme, Amgen, Janssen Oncology, Astra-Zeneca; provided consultancy to Boehringer Ingelheim, Sanofi, ADC Therapeutics; and received scientific advisory fee from Servier, Novartis, Roche, ADC Therapeutics; and received research funding from Rhizen Pharmaceuticals. RH received honoraria from Bristol-Myers Squibb, MSD, Gilead, Kite, Roche, Novartis, Janssen, and Celgene. All other authors declare that they have no conflict of interest.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Manson, G., Brice, P., Herbaux, C. et al. Risk of relapse after anti-PD1 discontinuation in patients with Hodgkin lymphoma. Eur J Nucl Med Mol Imaging 48, 1144–1153 (2021). https://doi.org/10.1007/s00259-020-05015-2
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DOI: https://doi.org/10.1007/s00259-020-05015-2