EBMT 2019 | Donor lymphocyte infusion monotherapy for HL after allo-SCT relapse

On Tuesday 26 March 2019, Oral Session 4 (OS4) took place at the 45^th Annual Meeting of the European Society of Blood and Marrow Transplantation (EBMT), Frankfurt, DE. During that session, Abstract OS4-8 was presented by Stephen Robinson from University Hospital Bristol, Bristol, UK on behalf of the EBMT Lymphoma Working Party (LWP).

Donor lymphocyte infusions (DLI) have been commonly used in patients with Hodgkin lymphoma (HL), who relapse after allogeneic stem cell transplantation (allo-SCT). However, there is limited data regarding the efficacy and safety of DLI in this population. In this retrospective, multicenter study, the investigators sought to address whether in HL, DLI results in favorable patient outcomes with a lower graft-versus-host disease (GvHD) incidence.

Study design & baseline characteristics

• N = 73 patients with HL from the EBMT database, who received DLI for relapse/progression or persistence of HL after allo-SCT 
• Female patients: n = 27
• Median age at allo-SCT (range): 30 (18−62) years
• Median time from diagnosis to allo-SCT (range): 2.9 (0.1−16) years
• Disease status at allo-SCT:
  • Complete response (CR): 22%
  • Partial response (PR): 36%
  • Refractory: 4%
  • Relapsed: 38%
• Conditioning regimen intensity:
  • Reduced intensity conditioning (RIC): 80% (n = 58)
  • Myeloablative conditioning (MAC): 20% (n = 15)
• Allogeneic cells were provided from:
  • Matched sibling: 73% (n = 53)
  • Mismatched family donor: 4% (n = 3)
  • Unrelated: 23% (n = 17)
• Good performance status at allo-SCT: n = 62 patients
• Median time from allo-SCT to relapse (range): 5.9 (1−36) months
• GvHD prophylaxis with anti-thymocyte globulin (ATG)/anti-lymphocyte globulin (ALG) or alemtuzumab was administered in 37% of patients (n = 27)

Key results

• Median number of DLI received by patients (range): 2 (1−7)
• Median dose of first DLI (range): 5 x 10⁶ (0.05-128 x 10⁶) CD3/kg
• Median time from allo-SCT to DLI (range): 6.4 (0.6−57) months
• Median time from relapse to first DLI (range): 33 (0−304) days
• DLI response assessment (n = 61 evaluable patients):
  • CR: 26% 
  • PR: 15% 
  • Stable disease (SD): 18% 
  • Progressive disease (PD): 41% 
• Overall survival (OS) at 36 months after first DLI: 44% (95% CI, 34−57%)
• OS at 72 months after first DLI: 29.8% (95% CI, 20.6−43.1%)
• Ten out of 16 patients achieving CR with DLI, remain alive in CR at 76 (range, 44−125) months
• Six out of 19 patients achieving a PR or SD with DLI, remain alive with active disease at 64 (range, 53−134) months
• After a median follow-up after first DLI of 72.2 months:
  • Patients remaining in CR: n = 12
  • Patients without the need of further therapy: n = 11
  • Patients who received additional anti-lymphoma therapy after DLI: n = 36
  • Patients alive: n = 21
  • Patients died: n = 50; due to:
    • Disease relapse or PD: n = 34
    • SCT-related reasons: n = 11
    • Secondary malignancy: n = 2
    • Other: n = 2
  • Four-year progression-free survival (PFS) estimate after first DLI: 19% (95% CI, 11−32)
  • Cumulative incidence of relapse at four years after first DLI: 46% (95% CI, 33−58)
  • Cumulative incidence of non-relapse mortality after first DLI: 35% (95% CI, 23−47)

Safety

• After DLI:
  • Acute GvHD (aGvHD; N = 73 at risk) prior to DLI was reported in 29% of patients
    • Grade III−IV aGvHD: 12%
  • Chronic GvHD (cGvHD; n = 65 at risk) prior to DLI was reported in 40% of patients
    • Extensive cGvHD: 22%
  •  Any type of GvHD occurence together with a response to DLI was observed in 54% of patients (P = 0.004) 
    • GvHD and CR: 81%
    • GvHD and PR: 66%
    • GvHD and SD: 27%
    • GvHD and PD: 44%

Conclusions

• DLI monotherapy resulted in an overall response rate of 41%, in patients with HL who had relapsed from allo-SCT. This demonstrated the existence of a graft-versus-HL effect of DLI
• Patients who achieved CR with DLI monotherapy also achieved prolonged PFS without additional anti-lymphoma treatment
• Prospective studies and further data analysis are needed to validate these results and the efficacy of DLI monotherapy in patients with relapsed HL