EBMT 2018 | Phase II trial on chidamide combination with HDC and ASCT for R/R and high-risk lymphoma

At the 44^th European Society for Blood and Marrow Transplantation (EBMT) annual meeting, on 19 March 2018, during the lymphoma oral session 1 (OS1), Abstract OS1-4 was presented, by Jie Ji, from the Department of Hematology, West China Hospital of Sichuan University, China, on the effects of chidamide and cladribine-gemcitabine-busulfan (CGB) combination during ASCT in patients with relapsed/refractory (R/R) and poor-risk lymphoma.

High-dose chemotherapy (HDC), like BEAM conditioning is one of the most commonly used regimens for R/R lymphoma patients undergoing autologous stem cell transplantation (ASCT), as it presents with acceptable safety and efficacy. Nevertheless, a big percentage of patients relapse after ASCT and thus, the unmet medical needs of those patients have led to the investigation of novel drug regimens. Building on the results from their pre-clinical study, the authors further evaluated in this single arm, phase II trial, the efficacy and safety of CGB high-dose chemotherapy together with the histone deacetylase inhibitor (HDACi), chidamide (Chi; ChiCGB). The trial involved R/R or high-risk patients undergoing ASCT with either Hodgkin (HL) or non-Hodgkin lymphoma (NHL). The primary endpoints of this study included progression-free survival (PFS), overall survival (OS) and safety.

Patient characteristics & study design

• N = 60 patients, 60% males
• Median age (range): 35 (16–63)
• Patient disease status:
  • In first complete response (CR): n = 34 (56.7%)
  • R/R patients: n = 26 (43.3%)
  • PET-positive tumor before treatment: n = 10 (16.7%)
• Patient diagnosis:
  • B-cell NHL patients: n = 28 (46.7%)
  • Natural Killer (NK) or T-cell lymphoma (NKTCL): n = 28 (46.7%)
  • HL patients (R/R): n = 4 (6.6%)
• ChiCGB chemotherapy dosing:
  • Chidamine: 30 mg on Days -7, -4, 0, +3, orally twice-weekly
  • Cladribine: 6 mg/m² from Days -6 to -2, IV
  • Gemcitabine: 2500 mg/m² on Days -6 and -2, 4 hours after cladribine
  • Busulfan: 3.2 mg/kg fixed dose from Days -6 to -3, IV
• Median number of peripheral-blood stem cells infused (range): 2.1 x 10⁶ /kg (1.0–11.6 x 10⁶ /kg)
• No maintenance therapy

 Key findings

• Median follow-up: 15.1 months
• OS and PFS for:
• Whole cohort:
  • Thirty-three-month PFS: 78.7%
  • Thirty-three-month OS: 91.5%
• For B-cell NHL vs NKTCL patients:
  • Thirty-three-month PFS: 89.3% vs 9% (P = 0.138)
  • Thirty-three-month OS: 100% vs 8% (P = 0.043)
• CR vs PR patients before ASCT:
  • Thirty-three-month PFS: 79.2% vs 24-month PFS: 71.4% (P = 0.168)
  • Thirty-three-month OS: 94.9% vs 24-month PFS: 71.4% (P = 0.0175)
• Double/triple expressor B-cell lymphoma:
  • Twenty-two-month PFS: 100%
  • Twenty-two-month OS: 100%
• Relapses: n = 9
  • Median relapse time (range): 6.5 (3.5–16.6) months
  • NKTCL: n = 6 (2 died, 2 relapsed with hemophagocytic lymphohistiocytosis (HLH) and died; 2 local relapse [1 salvaged by radio therapy in CR, the other is on radio therapy])
  • B-cell NHL: n = 2 (1 salvaged with rituximab + ibrutinib in CR; 1 salvaged with rituximab + ibrutinib + allogeneic SCT in CR)
  • HL: n = 1 (on anti-PD-1 therapy)

Safety

• Most common non-hematologic adverse events (AEs):
  • Febrile neutropenia: 73.3%
    • Infections: 2 bacteremias with Escherichia coli and 1 Herpes zoster infection one-month post-transplant)
  • Other AEs were mild and self-limited:
    • Grade 2 diarrhea: 38.3%
    • Grade 2 mucositis: 15%
    • Seizure: 1.7% (1 case with history of seizure)
  • No therapy-related mortality. Patients fully recovered from all AEs

Dr Ji concluded that HDC ChiCGB is a new promising well-tolerated and efficient regimen that might be used as consolidation therapy along with ASCT in R/R or high-risk lymphoma patients. Nevertheless, further studies building upon these phase II results are needed to confirm the efficacy and safety profile of ChiCGB, especially for B-cell NHL patients with genetic abnormalities (TEL/DEL).