Long Term Follow up of Patients Undergoing High Dose Chemotherapy and Autologous or Allogeneic Stem Cell Transplantation for Mantle Cell Lymphoma

Introduction: High Dose Chemotherapy and autologous stem cell transplantation (ASCT) or rarely allogeneic (alloPSCT) has been used for patients (pts) with Mantle Cell Lymphoma (MCL) in first complete remission (CR) for several decades. The long-term outcomes of patients receiving high dose chemotherapy and transplant more than a decade ago are outlined in this abstract.

Methods: A single center evaluation of patients with MCL who underwent either ASCT or allo-PSCT for MCL and were transplanted at least 12 years ago (range 1988 to 2012) and survived at least 5 years (yrs) post-transplant were analyzed. Subjects were compared based on time of relapse (< 5 yrs, 5-10 yrs, > 10 yrs, or no relapse) using a nonparametric Kruskal-Wallis test (continuous variable) or a Fisher's Exact Test (categorical data). For each variable of interest, Kaplan-Meier curves of overall survival (OS) were generated and compared using a log-rank test and when the p-value was significant, the Tukey-Kramer adjustment applied to the pairwise comparisons. We also reported the median OS with 95% confidence interval (CI) at 5, 10, 15 years as well as the hazard ratio. For PFS, cumulative incidence curves were generated and compared using Gray's test and when the p-value was significant, the Bonferroni adjustment applied to the pairwise multiple comparisons. Estimates of cumulative incidence with 95% confidence intervals were reported at various time points of interest.

Results: A total of 182 pts were transplanted during that time period with 109 surviving at least 5 yrs and the population of interest for this landmark analysis. The pts had a median age of 54.2 years (range 29-75). 75.2% were male and 98.2% were white. Of the 109 patients, 16 received an alloPSCT and 93 an auto PSCT. Peripheral stem cells (PSC) were used in 107 (98.2%) and only 2 (1.8 %) used bone marrow. There was no difference between time to relapse for patients based on their age at infusion (p=0.37), sex (p=.26), and histologic subtype of MCL (p=.23). The PFS initially appeared to be statistically significantly for age at transplant: 29-47 yrs compared to ages 61-75 (p= 0.048) but was insignificant in pairwise comparisons (p=0.059). There was no statistically significant difference in OS based on age at transplant ages 48-54 yrs, 55-60 yrs, 61-75 yrs compared to 29-47 yrs (p=.206). There was no statistically significant difference in OS for patients based on progression sites (nodal vs. extra-nodal) (p= 0.675). Three patients survived at least 5 years post auto-PSCT and then underwent alloPSCT at the time of relapse. Of the 3 patients, 2 died without an MCL relapse - due to infections or Graft-vs. Host Disease, and one had a second MCL relapse and died. There were 4 patients who relapsed >10 years after their autoPSCT. Site of relapse in these patients was nodal (N=1), testicular (N=1), missing (N=2).

Conclusions: In this landmark analysis of MCL patients, of the 109 surviving at least 5 years post- transplant, 51 patients progressed; the majority due to MCL relapse. However, 49/109 (45%) were alive at last contact (12-27 years post-transplant). PFS initially appeared to be statistically significant for age at transplant but was not significant by pairwise comparisons. For selected MCL patients, autoPSCT in CR1 may produce very long term disease-free survival.

Lunning:Bristol Myers Squibb: Consultancy, Research Funding; Abbvie: Consultancy; Genmab: Consultancy. Vose:Abbvie: Honoraria, Research Funding; Pfizer: Research Funding; Novartis: Honoraria; GenMab: Honoraria, Research Funding.