A Comparison of Gemcitabine/Clofarabine/Busulfan (Gem/Clo/Bu) Myeloablative Conditioning with Fludarabine/Melphalan (Flu/Mel) Reduced Intensity Conditioning for Allogeneic Stem-Cell Transplant (alloSCT) for Aggressive Lymphomas

Patients (pts) with aggressive lymphomas in refractory relapse are often considered for an alloSCT pursuing a graft-vs-lymphoma effect. While reduced intensity conditioning regimens have increased its safety, aggressive lymphomas often progress rapidly, partly due to tumor growth outpacing GVL. Outcomes are particularly poor for patients with active disease at alloSCT. Thus, development of safe more effective conditioning regimens for aggressive lymphomas is a major need. To this end we developed a new myeloablative regimen of Gem/Clo/Bu, which showed high activity and reduced toxicity for alloSCT (as reported in a separate abstract). We wished to compare the outcomes of pts enrolled in this trial with matched controls receiving Flu/Mel. METHODS We compared EFS and OS of pts with aggressive lymphomas enrolled in a phase I/II trial of Gem/Clo/Bu for matched donor alloSCT to our own concurrent controls treated with Flu/Mel. We utilized propensity score matching including the following variables: sex, age, donor type, diagnosis, response at alloSCT, disease risk and No. prior therapy lines. After matching, we estimated the survival curves by Kaplan-Meier, compared groups by log rank, and used the Cox proportional hazard model on the weighted sample to estimate the relative hazard ratios. RESULTS We compared 64 pts enrolled in the Gem/Clo/Bu trial between 11/2012-04/2021 to 113 controls treated with Flu/Mel between 01/2008-03/2022 (Table). The median follow-up of Gem/Clo/Bu pts was 80 months (mo) (range, 72-107) vs. 54 months (45-125) for controls. The median EFS times of Gem/Clo/Bu and control Flu/Mel patients were 12 mo (8-25.5) and 3.3 mo (2.8-10.6), respectively; their respective median OS times were 25 mo (15.5-N/A) vs 7.0 mo (3.3-37.7). The following were independent favorable outcome predictors: receiving Gem/Clo/Bu [hazard ratio (HR)0.38 (0.23,0.62), P=0.001 for EFS; HR 0.45 (0.27,0.73), P=0.01 for OS], Hodgkin diagnosis [HR 0.29 (0.12, 0.72), P=0.008 for OS], and response to prior salvage therapy [HR 0.35 (0.21,0.58), P<0.001 for EFS; HR 0.50 (0.31,0.83), P=0.007 for OS]. Conversely, >3 prior therapy lines [HR 2.13 (1.23, 3.70), P=0.007) was independently associated with worse EFS. CONCLUSION Gem/Clo/Bu results in improved EFS and OS as compared with Flu/Mel for pts with aggressive relapsed lymphoma receiving a matched alloSCT.