Refining RIST: long-term efficacy and safety of reduced-intensity SCT in relapsed MCL patients

In January 2018, Stephen P. Robinson, from the University Hospitals Bristol, Bristol, UK, and colleagues from the EBMT lymphoma working party, published online in Bone Marrow Transplantation a retrospective, long-term outcome analysis study on the effects of reduced-intensity allogeneic stem cell transplantation (RIST) in patients with relapsed mantle cell lymphoma (MCL).

RIST has mainly been used in MCL patients who relapse following first-line treatments, such as cytarabine, rituximab and autologous stem cell transplantation (autoSCT). Nevertheless, the long-term efficacy and safety of RIST remain unclear. This study sought to gather retrospective registry data of the largest patient cohorts, to examine the effects of RIST on MCL, after the longest ever reported median follow-up of 72 months. The primary endpoints of the study included overall survival (OS), progression-free survival (PFS), non-relapse mortality (NRM) and disease progression following RIST.

Patient characteristics

• Registered EBMT patients undergoing RIST for MCL, from January 2000 to December 2008
• N = 324
• Median age = 53 years
• Received prior autoSCT = 46%
• Received > 3 lines of prior therapy = 43%

Key findings

• Median follow-up = 72 months
• 1-year PFS = 51%
• 4-year PFS = 31%
• From multivariate analysis, worse PFS was associated with:
  • Chemorefractory disease at transplant (P < 0.001)
  • ≥ 3 prior lines of treatment (P < 0.001)
• 1-year OS = 62%
• 5-year OS = 40%
• From multivariate analysis, worse OS was associated with:
  • Chemorefractory disease at transplant (P < 0.001)
• No difference in PFS or OS if RIST was used as a first chemosensitive response or later in the disease course
• 1-year cumulative incidence of relapse/progression after RIST = 25%
• 5-year cumulative incidence of relapse/progression after RIST = 40%
• From multivariate analysis, higher risk of disease relapse/progression associated with:
  • T-cell depletion with CAMPATH treatment prior to RIST (RR = 2.59; CI, 1.56-4.30; P < 0.0002)
  • Total body irradiation (TBI) prior to RIST (RR = 1.59; CI, 1.01-2.51; P < 0.046)
• Rituximab prior to RIST associated with lower risk of relapse (RR = 0.56; CI, 0.36-0.88; P = 0.012)

Safety

• 98 deaths, attributed to non-relapse mortality (NRM), occurred at a median 4.5 months after RIST
• Reported NRMs included: graft-versus-host disease (GvHD) (16%), infections (34%), GvHD + infections (37%), multi-organ failure (6%), graft rejection (3%) and other causes/unknown (4%)
• 100-day NRM after RIST = 10%
• 1-year NRM after RIST = 24%
• NRM was significantly lower in patients receiving anti-thymocyte globulin (ATG/ALG) (RR = 0.58; CI, 0.35-0.97; P = 0.04)
• 100-day cumulative incidence of acute GvHD after RIST = 52%
• From multivariate analysis, lower risk of acute GvHD was associated with:
  • CAMPATH in conditioning regimen (HR = 0.46; CI, 0.27-0.77; P =0.004)
  • Older age
  • Chemosensitive disease
• 12-month cumulative incidence of chronic GvHD after RIST = 41%

In this retrospective study, a long-term follow-up of the largest MCL patient cohort having undergone RIST was presented. The main results of this study included a 1-year NRM of 24%, mainly attributable to GvHD and infections and a high relapse rate of 40%, 5-years after RIST. According to the authors, these results suggest that RIST could have curative potential for high-risk MCL patients, as an alternative to autoSCT and following appropriate toxicity management. Two unexpected results that might be of interest for future MCL treatment strategies, were also reported: (a) the protective effect of ATG/ALG conditioning; and (b) the deleterious effect of CAMPATH prior to RIST. Major limitations of this study include the retrospective basis of the collected data and the fact that only RIST cases between 2000–2008 were taken into consideration. Nevertheless, this study provides useful information for the successful management of MCL.