Large retrospective outcomes analysis of allo-HCT in relapsed FL by the EBMT lymphoma working party and CIBMTR lymphoma committee

The Lymphoma Working Party (LWP) of the European Bone Marrow Transplant (EBMT) and the lymphoma committee of the Center for International Blood and Bone Marrow Transplant Research (CIBMTR) collaborated on a study to assess long term outcomes of allogeneic hematopoietic stem cell transplantation (allo-HCT) in patients with follicular lymphoma (FL). The large retrospective analysis by Anna Sureda et al. was published in Cancer, on 9^th Feb 2018.

The study included 1567 patients (median age = 51, range 21–74 years) with FL who had human leukocyte antigen (HLA)-identical sibling or HLA-matched unrelated donor allo-HCT between 2001–2011. The majority of patients had received HLA-matched sibling donor allo-HCT (n = 1148, 73%) compared to unrelated well-matched HLA donor allo-HCT (n = 419, 27%). The primary endpoints of the study included; overall survival (OS), progression-free survival (PFS), transplant-related mortality (TRM) and disease relapse and progression.

Key Findings

• Median follow-up was 55 months
• 5-year OS probability = 61% (95% CI, 59%–64%), P = 0.13
• 5-year PFS probability = 52% (95% CI, 49%–55%)
• 5-year TRM cumulative incidence = 29% (95% CI, 26%–31%)
• 5-year cumulative incidence of disease relapse/progression = 19% (95% CI, 17%–22%)

In the multivariate analysis, several factors were identified that had significant associations with patient outcomes. Factors that adversely affected OS and PFS included:

• Age at HCT = OS relative risk (RR) 03 (1.02-1.04) P > 0.0001
• Grade 3 histology = OS RR 44 (1.13-1.83) P = 0.003, PFS RR 1.42 (1.15-1.76) P = 0.001
• High number of lines of prior therapy ≥5 = OS RR 41 (1.77-3.30) P < 0.0001, PFS RR 1.93 (1.46-2.55) P < 0.0001
• Chemo-refractory disease = OS RR 59 (1.30-1.95) P < 0.0001, PFS RR 1.54 (1.28-1.86) P < 0.0001
• Low Karnofsky performance score (KPS) <80 = OS RR 23 (1.52-3.25) P < 0.0001, PFS RR 1.78 (1.23-2.58) P = 0.002
• Myeloablative conditioning (MAC) regimens = OS RR 42 (1.16-1.73) P = 0.0006, PFS RR 1.36 (1.14-1.63) P = 0.0008

Additionally, age, chemo-resistant disease, high number of prior lines of therapy, low KPS and MAC were significantly associated with TRM and chemo-resistant disease and grade 3 histology were more likely to adversely affect disease relapse and progression.

Grade 2-4 Graft versus Host Disease (GVHD) at day 100 = 20% (95% CI, 18–22%) and at year 1 = 45% (95% CI, 42–48%). The authors noted that GVHD incidence was higher in the CIBMTR group, which may have been due to a higher frequency of matched unrelated donors in this group.

The study authors then conducted a risk analysis giving a score of low, intermediate and high risk to the factors identified in the multivariate analysis. Hazard ratio (HR) for treatment failure was 1.72 (95% CI, 1.24–2.43) P = 0.0014 when comparing high risk with intermediate risk patients.

The authors noted a plateau in the relapse curve showing that there was good disease control in this group of patients. Limitations of the study included; no distinction between grade 3a and 3b histologies, exclusion of transformed histologies, and that pre-transplant therapies, post-allo-HCT maintenance treatments and chimerism kinetics on outcomes were not assessed. The authors concluded that their study was the largest of its kind and it demonstrated good long-term outcomes for allo-HCT treated relapsed FL patients. They recommended that unrelated donor allo-HCT should be started earlier on in disease treatment and to avoid MAC regimens as it was associated with poorer outcomes.