Early response to first-line anti-PD-1 treatment in Hodgkin lymphoma: a PET-based analysis from the prospective, randomized phase II NIVAHL trial

Item Type:	Article
Title:	Early response to first-line anti-PD-1 treatment in Hodgkin lymphoma: a PET-based analysis from the prospective, randomized phase II NIVAHL trial
Creators Name:	Voltin, C.A. and Mettler, J. and van Heek, L. and Goergen, H. and Müller, H. and Baues, C. and Keller, U. and Meissner, J. and Trautmann-Grill, K. and Kerkhoff, A. and Fuchs, M. and Sasse, S. and von Tresckow, B. and Dietlein, M. and Borchmann, P. and Engert, A. and Kobe, C. and Bröckelmann, P.J.
Abstract:	PURPOSE: A primary analysis of the ongoing NIVAHL trial demonstrated unexpectedly high interim complete response rates to nivolumab-based first-line treatment in early-stage unfavorable Hodgkin lymphoma. However, biomarkers such as metabolic tumor volume (MTV) or total lesion glycolysis (TLG) and their change under treatment (∆MTV and ∆TLG), measured on positron emission tomography (PET), might provide additional relevant information for response assessment in this setting. Hence, the present analysis aimed to investigate early response to checkpoint inhibitor therapy beyond conventional criteria. PATIENTS AND METHODS: NIVAHL is a prospective, randomized phase II trial that recruited between April 2017 and October 2018. Patients in arm A and B were assessed for early treatment response after 2 courses of doxorubicin, vinblastine, and dacarbazine with 2 concomitant nivolumab infusions per cycle (N-AVD) and 4×nivolumab, respectively. In the present analysis, we included all 59 individuals with PET images available to the central review panel for quantitative analysis before April 30, 2019. RESULTS: At interim restaging, we determined a mean ∆MTV and ∆TLG of -99.8% each in arm A after 2×N-AVD, compared with -91.4% and -91.9%, respectively, for treatment group B undergoing 4×nivolumab. This high decrease in MTV and TLG was observed regardless of the initial lymphoma burden. CONCLUSIONS: Our study showed that nivolumab-based first-line treatment leads to rapid near-complete reduction of tumor metabolism in early-stage unfavorable Hodgkin lymphoma. Thus, PET-derived biomarkers might allow reduction or even omission of chemo- and radiotherapy. Furthermore, MTV and TLG could be also used to optimize immune checkpoint-targeting treatments in other cancers.
Keywords:	Hodgkin Lymphoma, Immunotherapy, PD-1 blockade, Response Assessment, Positron Emission Tomography
Source:	Clinical Cancer Research
ISSN:	1078-0432
Publisher:	American Association for Cancer Research
Volume:	27
Number:	2
Page Range:	402-407
Date:	January 2021
Official Publication:	https://doi.org/10.1158/1078-0432.CCR-20-3303
PubMed:	View item in PubMed

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