MCL

Maintenance rituximab after ASCT confers significant survival benefit in patients with MCL – a single-center experience by the City of Hope National Medical Center

In Biology of Blood and Marrow Transplantation, last month Matthew G. Mei from City of Hope National Medical Center, Duarte, California, USA, and colleagues published findings of their retrospective study, which aimed to determine prognostic factors for outcomes after Autologous Stem Cell Transplant (ASCT) in patients with Mantle Cell Lymphoma (MCL).

This single-center study included 191 consecutive patients with MCL who had undergone an ASCT at the City of Hope National Medical Center between January 1997 and November 2013. The median age of patients at diagnosis was 59 years (range, 33–76) and the majority (98%) had stage III or IV disease. Intermediate- or high-risk MIPI was observed in 52% of patients for who a MIPI score could be allocated (131/191).

The majority of patients had received 1 upfront therapy before ASCT (n=128, 67%) and 56% of patients (n=106) had received an upfront regimen that included high dose cytarabine, such as hyper-CVAD (n=93), the Nordic regimen (n=10), or both (n=3). ASCT was carried out in 144 patients (75%) in First Complete Remission (CR1), 28 patients (15%) in first PR, and 19 patients (10%) is a second remission or later. Regarding ASCT conditioning regimens, 101 patients (53%) received chemotherapy only based regimens and the remaining patients were administered radiation-based regimens. Most patients (92%, n=175) received rituximab before ASCT and 39% (n=75) were given maintenance rituximab after ASCT.

Key Highlights:
Treatment outcome:
  • Median follow-up of surviving patients = 6.3 years (range, 2.1–17.8)
  • 5-year estimated OS and PFS:
    • All pts: 71% (95% CI, 63–77%) and 53% (95% CI, 45–60%)
    • Pts in PET-negative CR1 at ASCT: 83% (95% CI, 73–89%) and 65% (95% CI, 55–74%)
    • Pts transplanted with disease status other than CR1 (n=47): 49% (95% CI, 33–63%) and 27% (95% CI, 15–41%)
    • Pts older than 65 years at diagnosis: 68% (95% CI, 50–80%) and 55% (95% CI, 38–69%)
  • 5-year cumulative incidence of relapse = 41% (95% CI, 34–48%)
  • Number of relapses = 83 (14 of these went on to receive allogeneic SCT); median time post-transplant = 2.1 years (range, 0.2–13.4)
  • Secondary malignancies reported in 7% of pts (n=14); 5 were therapy-related MDS or AML
  • Non-relapse mortality = 8% (n=16); due to secondary malignancy in 10 pts
Prognostic factors:
  • Maintenance rituximab post-transplant was the strongest prognostic factor for OS (Relative Risk [RR], 0.17; 95% CI, 0.07–0.38) and PFS (RR, 0.25; 95% CI, 0.14–0.44)
  • When assessed in pts in PET-negative CR1 at ASCT, maintenance rituximab remained significantly predictive for OS and PFS
  • In all pts who began rituximab maintenance ≤180 days post-ASCT vs those who did not receive rituximab maintenance:
    • 5-year estimated OS = 88% (95% CI, 75–95%) vs 63% (95% CI, 53–71%); P < 0.001
    • 5-year estimated PFS = 75% (95% CI, 60–85%) vs 45% (95% CI, 35–54%); P < 0.001
  • In pts in PET-negative CR1 who received maintenance rituximab ≤180 days post-ASCT vs pts in PET-negative CR1 who did not receive maintenance rituximab:
    • 5-year estimated OS = 93% (95% CI, 78–98%) vs 76% (95% CI, 62–86%); P = 0.009
    • 5-year estimated PFS = 78% (95% CI, 61–88%) vs 58% (95% CI, 43–70%); P = 0.0146
  • In pts aged 65 years or older, maintenance rituximab associated with superior PFS and a trend toward improved OS
  • In pts whose disease status at ASCT was higher than CR1, maintenance rituximab associated with both improved PFS and OS
  • Other variables that significantly associated with both improved PFS and OS included lack of blastoid variant histology and ASCT performed later than 2007
  • Radiation-based conditioning associated with improved OS and a trend toward improved PFS

The authors concluded their single-center study by stating that, regardless of the heterogeneity of the data, it was clear that maintenance with rituximab confers a huge benefit. The findings of this study contribute further to the ever growing amount of evidence that supports the use of maintenance rituximab for all MCL patients who have undergone an ASCT, no matter the patient’s age or type of upfront therapy they have received. Lastly, the group insist that future, prospective trials should aim to optimize maintenance therapy following ASCT for MCL.

Abstract:

High-dose therapy followed by autologous stem cell transplantation (ASCT) can improve outcomes for mantle cell lymphoma (MCL) but is associated with a high incidence of relapse. A retrospective study of 191 MCL patients who underwent ASCT at City of Hope was performed to examine prognostic factors for outcomes after ASCT. For all patients the 5-year overall survival (OS) was 71% (95% confidence interval [CI], 63% to 77%) and progression-free survival (PFS) was 53% (95% CI, 45% to 60%). The 5-year cumulative incidence of relapse was 41% (95% CI, 34% to 48%) with a continuous pattern of relapse events occurring at a median of 2.1 years (range, .2 to 13.4) after ASCT. In multivariate analysis, post-transplant maintenance rituximab was the factor most significantly associated with both OS (relative risk [RR], .17; 95% CI, .07 to .38) and PFS (RR, .25; 95% CI, .14 to .44). For the subset of patients who had positron emission tomography (PET) data available and were in a PET-negative first complete remission at ASCT (n = 105), maintenance rituximab was significantly associated with superior OS (RR, .17; 95% CI, .05 to .59) and PFS (RR, .20; 95% CI, .09 to .43). These results support a benefit with maintenance rituximab for all MCL patients treated with ASCT.

References
  1. Mei M.G. et al. Long-Term Results of High-Dose Therapy and Autologous Stem Cell Transplantation for Mantle Cell Lymphoma: Effectiveness of Maintenance Rituximab. Biology of Blood and Marrow Transplantation. 2017 Jul 18. pii: S1083-8791(17)30575-X. DOI: 10.1016/j.bbmt.2017.07.006. [Epub ahead of print].