EBMT 2018 | Idelalisib as bridging therapy in allo-SCT for FL patients

An oral abstract was presented at the 44^th European Society for Blood and Marrow Transplantation (EBMT) annual meeting on 19 March 2018 during the lymphoma oral session. Abstract OS1-6 was presented by Leopold Sellner from the University Hospital Heidelberg, Germany, on behalf of the EBMT Lymphoma Working Party (LWP). During this presentation, early events following allogeneic stem cell transplantation (allo-SCT) in follicular lymphoma (FL) patients treated with idelalisib, were discussed.

Idelalisib, a selective phosphatidylinositol 3-kinase δ inhibitor, is an approved oral drug for patients with relapsed or refractory (R/R) non-Hodgkin lymphoma, including FL. In this study, the feasibility and safety of allo-SCT following idelalisib treatment in R/R FL patients. The primary outcome was non-relapse mortality (NRM), while progression-free survival (PFS), overall survival (OS) and toxicity were considered as secondary endpoints.

Study design & patient characteristics

• N = 38 FL patients (63% male); Aged > 18 years registered in the EBMT database
  • Matched siblings: 24%
  • Unrelated match: 68%
  • Haploidentical: 8%
• Only FL patients who had an allo-SCT after idelalisib exposure:
  • Idelalisib treatment before allo-SCT as bridging therapy: n = 25 (66%)
  • Idelalisib in combination with anti-CD20: n = 9 (24%)
  • Idelalisib in combination with chemotherapy: n = 4 (11%)
• Median age at allo-SCT (range): 56 (34–71) years
• Median lines of treatment prior allo-SCT (range): 3 (1–8)
  • Autologous SCT: n = 20 patients (53%)
• Remission status at allo-SCT:
  • Complete response (CR): n = 7 (18%)
  • Partial response (PR) or stable disease (SD): n = 24 (63%)
  • Disease progression (PD) or primary refractory: n = 3 (8%)
  • Unknown: n = 4 (11%)
• Conditioning:
  • Alkylator-based conditioning: n = 27 (71%)
  • Total body irradiation (TBI): n = 11 (29%)
  • Alemtuzumab: n = 7 (18%)
  • Anti-thymocyte globulin (ATG): n = 18 (47%)
  • Reduced intensity conditioning (RIC): n = 28 (74%)

Key findings

• Median follow-up after allo-SCT (range): 9 (1–23) months
• All patients:
  • Non-relapse mortality (NRM) rate:
    • Six months post allo-SCT: 14%
    • Twelve months post allo-SCT: 32%
  • Incidence of relapse: 3/38 patients
    • Six-month relapse rate (RR): 8%
    • Twelve-month RR: 8%
  • PFS:
    • Six-month PFS: 79%
    • Twelve-month PFS: 62%
  • OS:
    • Six- month OS: 84%
    • Twelve-month OS: 62%
  • Patients in CR at last follow-up: n = 24 (63%)
• Patients receiving idelalisib as bridging therapy:
  • Non-relapse mortality (NRM) rate:
    • Six months post allo-SCT: 4%
    • Twelve months post allo-SCT: 24%
  • Incidence of relapse: 2/25 patients
    • Six-month relapse rate (RR): 8%
    • Twelve-month RR: 8%
  • PFS:
    • Six-month PFS: 88%
    • Twelve-month PFS: 70%
  • OS:
    • Six-month OS: 96%
    • Twelve-month OS: 71%
  • Patients in CR at last follow-up: n = 16 (64%)

Safety

• Causes of death:
• All patients:
  • Infections: n = 4
  • Graft-versus-host disease (GvHD): n = 3
  • Gastrointestinal (GI) toxicity: n = 1
  • Refractory patients: n = 2
• Patients receiving idelalisib as bridging therapy:
  • Infections: n = 2
  • Graft-versus-host disease (GvHD): n = 1
  • Gastrointestinal (GI) toxicity: n = 1
  • Refractory patients: n = 2

The authors concluded that idelalisib can be efficiently and safely used as bridging therapy for FL patients in allo-SCT, due to the high response rates reported. Nevertheless, the occurrence of early treatment-related deaths indicated that further studies with a longer follow-up focusing on the safety of idelalisib for patients undergoing transplantation are crucial. Such studies will enable the identification of the exact factors associated with NRM following idelalisib treatment in FL patients.