Interventional strategies based on interim 18FFDG-PET for advanced stage HL

On the 21 January 2018, Sylvain Carras, from the Hematology Department of Grenoble University Hospital, France, and the GOELAMS group, had the results of their phase II multicenter study (NCT00920153) published advanced online in the Journal of Clinical Lymphoma, Myeloma & Leukemia. The study assessed interventional treatment strategies based on interim PET imaging results, for advanced stage Hodgkin lymphoma.

With the current medical improvements, the management of Hodgkin lymphoma (HL) is considered as standard practice for most patients but still fails to cure 20-30% of patients with advanced stage HL. The aim of this study was to assess the efficacy and safety of adaptive front- and second-line treatment strategies based on interim 18F-fluorodeoxyglucose positron emission tomography (^18FFDG-PET) responses, in patients with advanced stage HL. The primary endpoints of the study included event-free survival (EFS), overall survival (OS) and safety.

Study overview

• Total N = 51 patients with advanced HL (29 males; 22 females)
• Median age = 41 (16–65)
• All patients received two courses of VABEM chemotherapy: vindesine (1mg/m²), adriamycin (33mg/m²), carmustine (BCNU; 14mg/m²), etoposide (200mg/m²) and methylprednisolone (120mg/m²)
• Following the two VABEM courses:
  • N = 49 patients received interim ^18FFDG-PET scanning:
    • N = 37 (76%) had negative ^18FFDG-PET scans:
      • Of those, n = 37 underwent one additional VABEM
      • Then n = 18 with initial bulky lesions (≥ 5cm) received additional radiotherapy
    • N = 12 (24%) had positive ¹⁸FDG-PET scans:
      • Of those, n = 11 received three courses of PDG: cisplatin (33mg/m²), gemcitabine (1000mg/m²) and dexamethasone (40mg) and peripheral blood stem-cell (PBSC) collection between the first and second PDG course
      • All ^18FFDG-PET-positive patients finally received high dose therapy (HDT) and autologous stem cell transplantation (ASCT)

Key results

• At the end of chemotherapy and radiotherapy:
  • Complete remission (CR): 88% (N=45/51)
  • Treatment failure: 12% (N=6/51)
• After two VABEM courses:
  • CR= 76% (N = 37/49)
• PDG CR = 83% (N = 10/12)
• Median follow-up = 5.3 years
• For the whole cohort:
  • 2-year EFS = 82.3% [95% CI (72.5–93.5%)]
  • 5-year EFS = 75.3% [95% CI (64–88.6%)]
  • 5-year OS = 85.3% [95% CI (76.3–96.1%)]
• For ^18FFDG-PET-negative patients:
  • 5-year EFS = 77.8% [95% CI (65.3–92.7%)]
  • 5-year OS = 88.2% [95% CI (78–99.8%)]
• For ^18FFDG-PET-positive patients:
  • 5-year EFS = 81.5% [95% CI (61.1–100%)]
  • 5-year OS = 91.7% [95% CI (77.3–100%)]

Safety

• Deaths associated with treatment: 6% (3/51; 1 pulmonary embolism, 1 pulmonary fibrosis and 1 secondary leukemia)
• Front-line-associated toxicity (VABEM):
  • ≥1 Grade 3-4 hematologic adverse events (AEs): 98% (50/51)
  • ≥1 Grade 3-4 non-hematologic AEs: 38% (19/51)
  • ≥ 1Grade 3-4 mucositis AEs: 35% (18/51)
  • ≥1 Grade 3-4 gastro-intestinal AEs: 8% (4/51)
• PDG-associated toxicity (salvage therapy):
  • ≥1 Grade 3-4 hematologic AEs: 34% (11/32)
  • ≥1 Grade 3-4 non-hematologic AEs: 0% (0/32)

The authors concluded that adapting the treatment strategy, depending on the results of interim PET scanning, could be beneficial for the management of advanced stage HL. They also demonstrated the efficacy of sequential therapy with chemotherapy and ASCT in high-risk HL patients. According to the authors, despite the high and constant VABEM-related toxicity, their adapted strategy made the treatment manageable, with only a small percentage of treatment-related deaths (6%). Nevertheless, they reported that a longer-follow up study is necessary for the assessment of late toxicity. The authors proposed that this strategy should be targeted at high-risk advanced stage HL patients with positive interim PET findings, following fist-line chemotherapy.