High‐dose chemo‐radiotherapy for relapsed or refractory Hodgkin lymphoma and the significance of pre‐transplant functional imaging

Abstract

We previously reported that three risk factors (RF): initial remission duration <1 year, active B symptoms, and extranodal disease predict outcome in relapsed or refractory Hodgkin lymphoma (HL). Our goal was to improve event-free survival (EFS) for patients with multiple RF and to determine if response to salvage therapy impacted outcome. We conducted a phase II intent-to-treat study of tailored salvage treatment: patients with 0 or 1 RF received standard-dose ifosfamide, carboplatin, and etoposide (ICE); patients with 2 RF received augmented ICE; patients with 3 RF received high-dose ICE with stem cell support. This was followed by evaluation with both computed tomography and functional imaging (FI); those with chemosensitive disease underwent high-dose chemoradiotherapy and autologous stem cell transplantation (ASCT). There was no treatment-related mortality. Compared to historical controls this therapy eliminated the difference in EFS between the 3 prognostic groups. Pre-ASCT FI predicted outcome; 4-year EFS rates was 33% vs. 77% for patients transplanted with positive vs negative FI respectively, p=0.00004, hazard ratio 4.61. Risk-adapted augmentation of salvage treatment in patients with HL is feasible and improves EFS in poorer-risk patients. Our data suggest that normalization of FI pre-ASCT predicts outcome, and should be the goal of salvage treatment.

Normalization of pre-ASCT, FDG-PET imaging with second-line, non–cross-resistant, chemotherapy programs improves event-free survival in patients with Hodgkin lymphoma

“…4 Finally, we have proposed that chemosensitive disease should be defined by pretransplant 18 fluorodeoxy glucose-positron emission tomography (FDG-PET) status; those patients with a negative scan have a 5-year EFS of 75% compared with 25% for those patients with improvement of CT but with persistent FDG-PET positivity. [4][5][6][7][8] Similar FDG-PET data were recently confirmed by the transplant group from Washington University. 9 The current comprehensive study incorporates non-cross-resistant SLT and individually tailored RT and HDT/ASCT.…”

Pre-transplant FDG-PET-based survival model in relapsed and refractory Hodgkin’s lymphoma: outcome after high-dose chemotherapy and auto-SCT

“…We had evaluated all these factors in our analysis. There are only two recent studies with 4100 patients who had FDG-PET before transplant, 15,25 but treatment offered in these studies are purely institutional research based; augmented chemotherapy with or without radiation and tandem transplant. Schot et al 8 reported 101 patients (78 various NHL and 23 HL), 77 of whom underwent HDC ASCT.…”

“…Studies reporting 20 or more HL patients in HDC ASCT setting are limited. [7][8][9][10][11][12][13][14][15]25,26 Many studies have combined various non Hodgkin's lymphoma (NHL) and HL together. Most studies analyzed FDG-PET as an individual risk factor rather than integrating it with all other factors.…”

Brentuximab Vedotin in Transplant-Naïve Relapsed/Refractory Hodgkin Lymphoma: Experience in 30 Patients

“…Several studies have shown that findings on positron emission tomography (PET) imaging performed after salvage chemotherapy and before ASCT, are a critical predictor of outcome in patients with relapsed/refractory (R/R) HL [15][16][17][18]. On the basis of these data, it is reasonable to consider patients with a PET-positive scan at transplantation as an unfavorable group to receive further treatment to improve their outcome.…”