Prognostic value of minimal residual disease among patients with classical Hodgkin lymphoma undergoing autologous stem cell transplantation

Abstract

Improved biomarkers are needed to guide patient selection for autologous stem cell transplantation (ASCT) and post-ASCT maintenance therapies in relapsed/refractory classical Hodgkin lymphoma (cHL). To assess the prognostic value of minimal residual disease (MRD) using immunoglobulin-based high-throughput sequencing (Ig-HTS), we analyzed pre- and post-ASCT peripheral blood and pre-ASCT apheresis stem cell (ASC) samples in 36 cHL patients. A tumor clonotype was detected in only 12 patients (33%). Among these patients, MRD within plasma samples was closely associated with impending relapse. All patients (n = 3) with detectable MRD in any post-ASCT plasma sample relapsed (100% specificity), and MRD was not detected in any patients in remission. MRD testing from cellular specimens (peripheral blood mononuclear cell or ASC samples) was not associated with relapse. In this small cohort, plasma-based MRD testing appeared to be a promising biomarker in cHL, but given low clonotype detection rates with Ig-HTS, alternative MRD approaches should be investigated.

Keywords:

• Minimal residual disease
• classical Hodgkin lymphoma
• circulating tumor DNA (ctDNA)
• autologous stem cell transplantation

Acknowledgements

PA and RWM would like to acknowledge support from the Harold and Virginia Lash Grant Program. RWM would like to acknowledge support from an American Society for Transplantation and Cellular Therapy New Investigator Award and a Lymphoma Research Foundation Clinical Investigator Career Development Award. We would also like to thank Allison Jacobs at Adaptive Biotechnologies for her insight and collaboration. This research was also supported in part by a research grant from Investigator-Initiated Studies Program of Merck Sharp & Dohme LLC. The opinions expressed in this paper are those of the authors and do not necessarily represent those of Merck Sharp & Dohme LLC.

Author contributions

ET, RWM, and PA designed the research study and performed the research study. ET and RWM analyzed the data. RR aided in statistical analysis and swimmer’s plot development. ET and RWM wrote the paper. ET, RR, EJ, KM, JLC, DCF, EJ, CAJ, AIK, ASL, OOO, PD, YN, RMJ, Y-BC, K-JCB, AC, AFH, PA, and RWM performed research and reviewed the paper.

Disclosure statement

ET, RR, EJ, KM, DCF, AIK, ASL, OOO, RMJ, KCB, and AC – none. JLC – consulting: Incyte, Karyopharm. Research funding: Bayer, Abbvie, Roche, Merck; EJ – consulting: Syros, Takeda. Research funding: Acerta, Janssen, Novartis, Pharmacyclics; CAJ – consulting: Kite/Gilead, Novatis, BMS/Celgene, Precision Biosciences, Nkarta, bluebird bio, Epizyme, Lonza, Abbvie, Ipsen. Research funding: Kite/Gilead, Pfizer; PBD – advisory board: Kite/Gilead; YN – consulting: Affimed, Novonordisk. Research funding: Novartis, Biosecura, Astra-Zeneca, Affimed, Takeda; Y-BC– consulting: Incyte, Jasper, Gamida Cell, Daiichi, Celularity, Equilium, Actinium; AFH – consulting: Bristol Myers Squibb, Genentech, Merck, Seattle Genetics, AstraZeneca, Karyopharm, ADC Therapeutics, Takeda, Tubulis. Research funding: Bristol Myers Squibb, Genentech, Merck, Seattle Genetics, KiTE Pharma, Gilead Sciences, AstraZeneca, ADC Therapeutics; PA – consulting: Merck, BMS, Pfizer, Affimed, Adaptive, Infinity, ADC Therapeutics, Celgene, Morphosys, Daiichi Sankyo, Miltenyi, Tessa, GenMab, C4, Enterome, Regeneron, Epizyme, Astra Zeneca, Genentech. Research funding (institutional): Merck, BMS, Affimed, Adaptive, Roche, Tensha, Otsuka, Sigma Tau, Genentech, IGM, Kite. Honoraria: Merck, BMS; RWM – consulting: Genmab, Adaptive Biotechnologies, BMS. Research funding: Bristol Myers Squibb, Merck, Genentech/Roche, Genmab.

Additional information

Funding

PA and RWM would like to acknowledge support from the Harold and Virginia Lash Grant Program. RWM would like to acknowledge support from an American Society for Transplantation and Cellular Therapy New Investigator Award and a Lymphoma Research Foundation Clinical Investigator Career Development Award.