Evaluating the PET Parameters SUVmax and TMTV in the Setting of Autologous Stem Cell Transplantation for DLBCL

Introduction

Where tolerated, high dose chemotherapy supported by autologous stem cell transplantation (ASCT) is the standard of care for patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL). Disease recurrence post-ASCT however is common and carries an extremely poor prognosis, highlighting the need for improved pre-transplant prognostic stratification. This study investigates the prognostic utility of the PET parameters total metabolic tumour volume (TMTV) and standardised uptake value (SUV)max in the peri-transplant setting.

Methods

125 patients underwent ASCT for relapsed or refractory DLBCL between 1/1/2002 and 31/1/2017 at the Peter MacCallum Cancer Centre. All patients received multi-agent salvage immuno-chemotherapy before proceeding to ASCT. 58 patients were treated with peri-transplant radiotherapy, with indications including incomplete response post-salvage therapy, and bulky and/or localised disease. 122 patients had their treatment response assessed with PET. TMTV and SUVmax were measured at time of primary disease relapse/progression prior to salvage immuno-chemotherapy (pre-salvage PET) and post-salvage immuno-chemotherapy prior to ASCT (pre-ASCT PET). 93 patients had pre-salvage and pre-ASCT PETs available for TMTV and SUVmax measurement.

Results

Median follow up was 5.6 years. The 5-year progression free survival (PFS) and overall survival (OS) were 52% (95% CI: 42-60) and 65% (95% CI: 56-73). In patients demonstrating complete metabolic response (CMR) and non-CMR on pre-ASCT PET the 5-year PFS was 58% (95% CI: 44-70) and 44% (95% CI: 29-57) respectively. The 5-year OS with CMR and non-CMR on pre-ASCT PET was 73% (95% CI: 59-83) and 54% (95% CI: 39-67).

TMTV and SUVmax were investigated as potential prognostic factors in the peri-transplant setting. In this patient group, pre-salvage TMTV and SUVmax were not found to be of prognostic significance. Pre-salvage TMTV and SUVmax PFS hazard ratios (HR)s were 1.06 per 100ml (95% CI:0.96-1.17; p = 0.27) and 1.00 (95% CI: 0.98-1.03; p = 0.78) respectively, and OS HRs were 1.10 per 100ml (95% CI: 0.86-1.18; p = 0.07) and 1.02 (95% CI: 0.96-1.04 p = 0.24). In contrast, pre-ASCT TMTV was a significant negative prognostic factor for both PFS (HR = 1.22 per 100ml; 95%CI: 1.10-1.37; p < 0.001) and OS (HR = 1.96 per 100ml; 95% CI: 1.38-2.79; p < 0.001). Pre-ASCT SUVmax similarly demonstrated a negative association with PFS (HR = 1.07; 95% CI: 1.04-1.10; p < 0.001) and OS (HR of 1.08 ; 95% CI: 1.04-1.11; p < 0.001). In addition to the TMTV and SUVmax absolute values, the relative change from pre-salvage to pre-ASCT PET was investigated for prognostic value. No significant association with PFS or OS was demonstrated for the relative change of either parameter. The relative change in TMTV had a HRs of 1.21 (95% CI: 0.54- 2.72; p = 0.65) and 1.15 (95% CI: 0.45-2.93; p = 0.77) for PFS and OS respectively, and relative change in SUVmax had a HRs of 1.30 (95% CI: 0.68- 2.50; p = 0.43) and 1.20 (CI 95% 0.57-2.54; p = 0.64) for PFS and OS.

Conclusion

As prognostic tools, pre-ASCT TMTV and SUVmax were both predictors for PFS and OS. In contrast, pre-salvage TMTV and SUVmax did not demonstrate an association with PFS or OS, reinforcing the prognostic significance of the pre-ASCT PET scan. The relative change in SUVmax and TMTV were similarly not associated with PFS and OS. These findings indicate that in the context of TMTV and SUVmax measurement, residual disease on pre-ASCT PET may be of greater predictive value than degree of response to salvage immuno-chemotherapy. While TMTV and SUVmax have primarily been studied in the context of first-line therapy for DLBCL, these results suggest a promising prognostic role for these PET parameters in the peri-transplant setting.