Early Response to First-Line Anti–PD-1 Treatment in Hodgkin Lymphoma: A PET-Based Analysis from the Prospective, Randomized Phase II NIVAHL Trial
- 15 January 2021
- journal article
- research article
- Published by American Association for Cancer Research (AACR) in Clinical Cancer Research
- Vol. 27 (2), 402-407
- https://doi.org/10.1158/1078-0432.ccr-20-3303
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
Funding Information
- Bristol-Myers Squibb
This publication has 19 references indexed in Scilit:
- iRECIST: guidelines for response criteria for use in trials testing immunotherapeuticsThe Lancet Oncology, 2017
- Refinement of the Lugano Classification lymphoma response criteria in the era of immunomodulatory therapyPublished by American Society of Hematology ,2016
- Cancer-related fatigue in patients with and survivors of Hodgkin's lymphoma: a longitudinal study of the German Hodgkin Study GroupThe Lancet Oncology, 2016
- Cumulative burden of cardiovascular morbidity in paediatric, adolescent, and young adult survivors of Hodgkin's lymphoma: an analysis from the St Jude Lifetime Cohort StudyThe Lancet Oncology, 2016
- Nivolumab for classical Hodgkin's lymphoma after failure of both autologous stem-cell transplantation and brentuximab vedotin: a multicentre, multicohort, single-arm phase 2 trialThe Lancet Oncology, 2016
- Second Cancer Risk Up to 40 Years after Treatment for Hodgkin’s LymphomaNew England Journal of Medicine, 2015
- Results of a Trial of PET-Directed Therapy for Early-Stage Hodgkin’s LymphomaNew England Journal of Medicine, 2015
- Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano ClassificationJournal of Clinical Oncology, 2014
- Omitting Radiotherapy in Early Positron Emission Tomography–Negative Stage I/II Hodgkin Lymphoma Is Associated With an Increased Risk of Early Relapse: Clinical Results of the Preplanned Interim Analysis of the Randomized EORTC/LYSA/FIL H10 TrialJournal of Clinical Oncology, 2014
- Report on the First International Workshop on interim-PET scan in lymphomaLeukemia & Lymphoma, 2009