Remission Duration ≤ 12 Months for Early Relapsed and Refractory Follicular Lymphoma Is Predictive of Early Failures Post-High Dose Therapy and Autologous Stem Cell Rescue

Introduction:  Follicular lymphoma (FL) is an indolent non-Hodgkin lymphoma characterized by high response rates and long response duration(s) to therapy.  In the relapsed/refractory setting (rel/ref), high-dose therapy and autologous stem cell rescue (HDT-ASCR) and non-myeloablative (NMA) allogeneic stem cell transplantation (alloSCT) are definitive therapies shown to provide long term disease free intervals.   To date, there remains an inherent difficulty in deciding the appropriate consolidative transplant modality in rel/ref FL.  Therefore, we conducted an analysis of clinical features of FL pts undergoing first HDT-ASCR or alloSCT.

Methods:  We retrospectively reviewed all pts with rel/ref FL that proceeded to HDT-ASCR or NMA alloSCT at MSKCC between 2006 and 2010.  Chemosensitive disease was defined as a partial response (PR) or complete response (CR) to the last treatment regimen prior to transplant by computed tomography scans per IWG Criteria.  Events were defined as progression of FL or death from any cause.  Event-free survival (EFS) and overall-survival (OS) were estimated using Kaplan-Meier method.

Results:  We identified 40 pts with rel/ref FL who had HDT-ASCR (N=20) or alloSCT (N=20).  Pts characteristics are outlined in the table below:

 

Patient Characteristics	HDT-ASCR n=20	alloSCT n=20
Median age in years (range)	51 (33-70)	55 (34-69)
Median number of previous lines of therapy (range)	2 (2-4)	3 (2-7)
Chemosensitive	19/20 (95%)	20/20 (100%)
CR	8	7
PR	11	13
Median remission duration (months) prior to re-induction therapy	11.5 (0*-31)	5 (0*-12)
Remission duration ≤ 12 months from re-induction therapy	11/20 (55%)	20/20 (100%)

                                    *Denotes chemorefractory disease prior to re-induction

The median follow-up for survivors is 34 months.  The estimated 3-year EFS and OS was 60% and 62% with HDT-ASCR and 79% and 85% with alloSCT respectively (p=ns).  FL pts with remission duration ≤ 12 months prior to re-induction therapy proceeding to consolidative HDT-ASCR had significantly shorter EFS compared to those pts with previous remission duration > 12 months (p<0.05, figure 1).  Furthermore, when HDT-ASCR and alloSCT pts with a previous remission duration ≤ 12 months prior to re-induction therapy were compared the estimated 3-year EFS was 79% for alloSCT and 36% for HDT-ASCR (p<0.03).  With relatively short follow-up, there was no difference in OS for these two groups. 

Conclusion:  The management of rel/ref FL remains a clinically complex topic.  In this exploratory analysis we demonstrated that remission duration of ≤ 12 months prior to re-induction chemotherapy is suggestive of inferior disease control with HDT-ASCR.  Longer follow-up is necessary to determine the OS impact.  Given the relatively unfavorable pre-transplant characteristics of the alloSCT cohort, FL appears to be exquisitely sensitive to an allogeneic effect.