EBMT 2018 | Efficacy and safety of lenalidomide combined with R-ESHAP regimen in DLBCL patients with relapsed or refractory disease

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 OS1-3 was presented, by Mónica Baile, from the Hospital Universitario de Salamanca/IBSAL, Hematology, Salamanca, Spain regarding the latest findings from the Phase II GELTAMO study.

This study assessed the safety and efficacy of lenalidomide’s addition to R-ESHAP regimen (LR-ESHAP) in diffuse large B-cell lymphoma (DLBCL) patients with relapsed or refractory disease after rituximab-containing therapy. The primary endpoints for this study included the overall response rate (ORR) after 3 cycles of LR-ESHAP. The secondary objectives were the complete response (CR), event free-survival (EFS) and overall survival (OS).

Study design:

• Eligibility for:
  • Relapsed or refractory DLBCL patients, confirmed by histology
  • Rituximab as a first-line treatment and anthracycline-containing regimen chemotherapy
  • Positive tumor lesions confirmed by PET/CT
  • Eastern Cooperative Oncology Group (ECOG) with a score <3
• Dosing (LR-ESHAP):
  • Three cycles of lenalidomide at 10 mg on days 1 to 14 of every 21–day cycle
  • R-ESHAP at standard doses:
    • Rituximab at 375 mg/m² on day 1 or 5
    • Etoposide at 40 mg/m² on days 1–4
    • Methylprednisolone at 500 mg/day on days 1–5
    • Citarabin at 2000 mg/m² on day 5
    • Cisplatin at 25 mg/m²/day on days 1–4)
• BEAM conditioning with autologous stem-cell transplantation (ASCT) given to responding patients:
  • Carmustine at 300mg/m² on day 6 prior to transplant (trx);
  • Etoposide at 100mg/m²/12h on days 5 and 2 prior to trx;
  • Citarabin at 100mg/m2/12h on days 5 and 2 prior to trx
  • Melphalan at 140 mg/m² on day 1 prior to trx
• Classification of cell of origin (COO) based on Hans' algorithm and digital quantitative PCR (LymphC2x, Nanostring)

Patients characteristics:

• N (global) = 46 patients; phase I = 12 patients and phase II = 34 patients
• Median age (range) = 58 (23-69)
• Patient disease status (n):
  • Partial response (PR) = 13
  • Stable disease (SD) or partial disease (PD) = 17
  • Relapsed disease = 16

Key Findings:

• N (evaluable-received the planned three cycles of treatment) = 40 patients
• Stem cell mobilization: n = 42 patients; successful in 39 patients
• ASCT: n (global population) = 28 patients
• Response rates (global population vs evaluable population):
  • Overall response rate (ORR; %) = 65 vs 71
  • Complete remission (CR; %) = 37 vs 40
  • Partial response (PR; %) = 28 vs 30
  • Stable disease (SD; %) = 2 vs 3
  • Progression disease (PD; %) = 24 vs 26
• Clinical outcomes (ORR vs CR, %):
  • Early relapse (< than 12 months) = 80 in both groups
  • Late relapse = 82 vs 54
  • PR = 77 vs 31 (P = 0.003)
  • Refractory disease: <PR with first-line = 41 vs 18 (P = 0.02)
• Median follow-up (range): 15 months
• Whole cohort:
  • Two-year EFS: 50%
  • Two-year OS: 49%
• Response rates according to cell of origin (COO):
  • Based on Hans' algorithm (germinal center (GC); n = 22 vs non-GC; n = 9):
    • ORR (%) = 64 vs 44 (P > 0.1)
    • CR (%) = 32 vs 22 (P > 0.1)
  • Based on quantitative PCR (GC; n = 19 vs activated B cell-like (ABC); n = 6):
    • ORR (%) = 63 vs 50 (P > 0.1)
    • CR (%) = 42 vs 33 (P > 0.1)

Safety:

• Most common adverse events (AEs; n= 42):
  • Grade 3 febrile neutropenia: n = 14
  • Grade 3 infections: n = 13
• Other less common AEs:
  • Grade 3 thrombosis: n = 3
  • Grade 3 renal toxicity: n = 2
  • Grade 2 neutropenia: n = 2
• AES in transplanted patients (n = 8): graft failure (n = 1); septic shock (n = 2), febrile neutropenia (n = 1), respiratory infection (n = 1), right pneumonia (n = 1), respiratory infection (n = 1) and papillary thyroid carcinoma (n = 1)

This study demonstrated the feasibility of LR-ESHAP, producing high response rates in refractory and relapsed DLBCL patients. Additionally, this regimen was safe enabling a high percentage of patients to receive autologous transplant. It was also found that refractory patients fared worse than patients with relapsed disease, highlighting the need of alternative treatment for patients with primary refractory disease.