Abstract
Introduction: PD-1 blockade is effective in relapsed/refractory classical Hodgkin lymphoma (R/R cHL). To date, early metabolic response has been the best predictor of outcome in this setting. In this study, we explored additional baseline and early FDG PET-CT parameters as potential prognosticators in patients with R/R cHL treated with single agent nivolumab in the CHECKMATE 205 trial.
Methods: Available PET-CT scans from patients without progression (by IRC Lugano 2007 criteria) by week (wk) 17 were retrospectively reviewed by 2 readers blinded to outcome. Baseline and wk17 metabolic parameters in tumour and healthy tissues uninvolved by lymphoma were examined for their association with PFS using Cox regression.
Results: Baseline scans have been reviewed to date for 57 patients, and 49 patients at wk17 from 19 centres, with median follow up 60.7 months. There was a significant association between baseline maximum standardised uptake value (SUV) and PFS [HR 1.48 (95% CI 1.09–2.02) p = 0.012], wk17 Deauville score (DS) [Log-rank trend p = 0.0008] and Lugano response [HR 4.83 PMR vs. CMR (1.37–17.03) p = 0.014]. There was possible but non-significant association between the maximum distance between lesions at baseline and PFS (p = 0.07), but not for baseline metabolic tumour volume (MTV), wk17 MTV, change in MTV or change in SUVmax. Interestingly, baseline bone marrow and splenic uptake in uninvolved organs were associated with PFS, but not uptake in other uninvolved organs (liver, mediastinal blood pool, bowel, skeletal muscle and adipose tissue). The effect of baseline SUVmax remained very similar even in Lugano responders (CMR/PMR, n = 33) at wk17 HR 1.45 (95% CI 0.90—2.33) 1.45 (95% CI 0.90–2.33), though with the reduced sample size (n = 33) did not reach significance p = 0.13.
Conclusion: Baseline SUVmax and week 17 PET-CT response in this prospectively acquired clinical trial dataset, but not MTV, were significantly associated with PFS in patients with R/R HL treated with nivolumab. The lack of an apparent prognostic impact of MTV contrasts with its prognostic value in chemotherapy-based treatments, and lends caution for trial designs using checkpoint-based treatment that stratify patients based on MTV. Baseline uptake in uninvolved bone marrow and spleen, which may reflect immune activation state, may be potential biomarkers of immunological response with checkpoint inhibitors. This phenomenon, and the underlying immunologic mechanism, warrant further exploration.
Keywords: diagnostic and prognostic biomarkers, Hodgkin lymphoma, PET-CT
Methods: Available PET-CT scans from patients without progression (by IRC Lugano 2007 criteria) by week (wk) 17 were retrospectively reviewed by 2 readers blinded to outcome. Baseline and wk17 metabolic parameters in tumour and healthy tissues uninvolved by lymphoma were examined for their association with PFS using Cox regression.
Results: Baseline scans have been reviewed to date for 57 patients, and 49 patients at wk17 from 19 centres, with median follow up 60.7 months. There was a significant association between baseline maximum standardised uptake value (SUV) and PFS [HR 1.48 (95% CI 1.09–2.02) p = 0.012], wk17 Deauville score (DS) [Log-rank trend p = 0.0008] and Lugano response [HR 4.83 PMR vs. CMR (1.37–17.03) p = 0.014]. There was possible but non-significant association between the maximum distance between lesions at baseline and PFS (p = 0.07), but not for baseline metabolic tumour volume (MTV), wk17 MTV, change in MTV or change in SUVmax. Interestingly, baseline bone marrow and splenic uptake in uninvolved organs were associated with PFS, but not uptake in other uninvolved organs (liver, mediastinal blood pool, bowel, skeletal muscle and adipose tissue). The effect of baseline SUVmax remained very similar even in Lugano responders (CMR/PMR, n = 33) at wk17 HR 1.45 (95% CI 0.90—2.33) 1.45 (95% CI 0.90–2.33), though with the reduced sample size (n = 33) did not reach significance p = 0.13.
Conclusion: Baseline SUVmax and week 17 PET-CT response in this prospectively acquired clinical trial dataset, but not MTV, were significantly associated with PFS in patients with R/R HL treated with nivolumab. The lack of an apparent prognostic impact of MTV contrasts with its prognostic value in chemotherapy-based treatments, and lends caution for trial designs using checkpoint-based treatment that stratify patients based on MTV. Baseline uptake in uninvolved bone marrow and spleen, which may reflect immune activation state, may be potential biomarkers of immunological response with checkpoint inhibitors. This phenomenon, and the underlying immunologic mechanism, warrant further exploration.
Keywords: diagnostic and prognostic biomarkers, Hodgkin lymphoma, PET-CT
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Hematological Oncology |
| Vol/bind | 41 |
| Sider (fra-til) | 92-93 |
| Antal sider | 2 |
| ISSN | 0278-0232 |
| DOI | |
| Status | Udgivet - 2023 |