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3323 Autologous Vs. Allogeneic Stem Cell Transplantation in Double-Expressor Lymphoma

Program: Oral and Poster Abstracts
Session: 723. Clinical Allogeneic and Autologous Transplantation: Late Complications and Approaches to Disease Recurrence: Poster III
Hematology Disease Topics & Pathways:
Biological, Diseases, Lymphoma (any), Therapies, Non-Hodgkin Lymphoma, DLBCL, Lymphoid Malignancies, Clinically relevant, transplantation
Monday, December 7, 2020, 7:00 AM-3:30 PM

Issa F. Khouri, MD1, Stephen K. Gruschkus, PhD, MPH2*, Celina Ledesma3*, Paolo Anderlini3, Qaiser Bashir3*, May Daher4, Swami P. Iyer, MD5, David Marin1, Rohtesh Mehta3*, Amanda L. Olson4, Uday R. Popat, MD4, Felipe Samaniego, MD6, Muzaffar H. Qazilbash, MD1,3, Jin S. Im4, Gabriela Rondon1, Richard E. Champlin, MD1, Alison Gulbis7* and Ken H. Young8

1Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
2Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX
3Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas M.D. Anderson Cancer Center, Houston, TX
4Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
5Department of Lymphoma and Myeloma, University of Texas M.D. Anderson Cancer Center, Houston, TX
6Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX
7Pharmacy, The University of Texas M.D. Anderson Cancer Center, Houston, TX
8Duke Medical Center and Duke Cancer institute, Duke University School of Medicine, Durham, NC

Purpose: Dual expression of MYC and BCL2 proteins (Double Expressor Lymphoma-[DEL]) is an important prognostic factor in patients (pts) with diffuse large B-cell lymphoma (DLBCL) who are treated with standard chemo-immunotherapy. Studies have suggested that pts with these biomarkers have inferior survival compared to pts who were non-DEL after autologous stem cell transplantation (autoSCT). For this reason, allogeneic stem cell transplantation (alloSCT) has been advocated for its potential graft-versus-lymphoma effect. Data are limited however regarding the outcomes in pts with relapsed DEL who were treated with autoSCT vs. alloSCT.

Methods: Data from pts with relapsed DEL/DLBCL who underwent auto- and alloSCT as their first transplant at our center and in whom archived tumor material was available were analyzed. Cutoff values of 40% for MYC and 70% for BCL2 were established by immunohistochemistry (IHC). The majority of autoSCT pts (84%) underwent chemo-mobilization of stem cells with rituximab (R) for in-vivo purging; rituximab was also given on days+1 and +8 with BEAM conditioning (J Clin Oncol 2005; 23:2240-7; Clin Cancer Res 2018; 24:2304-11). Conditioning for the alloSCT was myeloablative (n=16, 50%), reduced-intensity (n=6, 19%), and nonmyelablative (n=10,31%). The study was IRB-approved at our center. Kaplan-Meier analysis and corresponding log-rank/Gray’s tests were used to estimate and compare overall survival (OS), progression-free survival (PFS), and cumulative incidence (CI) of non-relapse mortality and relapse by SCT group. Standard multivariable Cox regression was used to evaluate associations between SCT type and OS/PFS after controlling for differences in baseline characteristics and cause-specific multivariable Cox regression was used for competing-risk outcomes [non-relapse mortality (NRM) and relapse].

Results: The study included 161 autoSCT and 32 alloSCT pts treated between 2000-2018. Median age was 59 (range,18-80) and 55 years (range, 21-66), respectively (P=0.009). Male gender was 62.7 vs 50.0%, respectively (P= 0.234). Fifty-one (32.5%) autoSCT pts and 9 (28.1%) alloSCT pts had an elevated serum LDH (P= 0.683) and 41/148 (27.7%) autoSCT and 11/25 (44.0%) alloSCT pts were PET-positive at study entry (P=0.106). The time from diagnosis to transplant was 20.0 and 25.2 months, respectively, (P=0.068), and the distribution of the years of transplant was similar between both groups (P=0.317). Significant differences between treatment groups were observed for prior number of chemotherapies, disease status, stage, and HCT-CI score at transplant. Pts. receiving alloSCT were more heavily pretreated [median 3 prior therapies, (range 1-8) vs. a median of 2, (range 1-6); P=0.0001], had more advanced stage III-IV disease (P=0.035), and more refractory disease (P=0.010) at transplant. In addition, a higher percentage of alloSCT pts had an HCT-CI of >4 (28.1% vs. 10.2%, P=0.018) at study entry. Allogeneic transplant characteristics included matched siblings (n=18; 56.3%), matched unrelated (n=13, 40.6%) and haplo-identical (n=1, 3.1%) donors. With a median follow-up for autoSCT surviving pts of 65 months (range, 5-217 months) and 93 months (range, 34--124 months) for alloSCT pts, the OS at 5-years were 59% and 34%, respectively (P= 0.0001) (Figure1). The PFS rates at 5-years were 49% and 31%, respectively (P = 0.002). AutoSCT had a similar rate of relapse to alloSCT but a lower rate of NRM. The 5-year CI of relapse was 37% vs 28%, respectively (P = 0.611) and the 5-year NRM rates were 14% vs 41 % (P=0.0001), respectively (Figure 2). The associations between SCT group and outcomes persisted after adjusting for differences between groups (alloSCT vs. autoSCT HR= 3.46/p=0.0004 for OS; HR=2.67/p=0.005 for PFS; HR=4.74/p=0.009 for NRM; HR=2.22/p=0.080 for relapse). The 100-day CI of grade II-IV and III-IV acute GVHD in the alloSCT group was 37.5 and 9.4%, respectively. The 1-year CI of chronic GVHD was 25.0%.

Conclusions: This study is the first to show that autoSCT confers a superior survival in pts with relapsed DEL/DLBCL compared to alloSCT. Our conclusions are supported by long-term follow-up. The use of novel nonmyeloablative regimens in a larger number of pts receiving an alloSCT and ongoing studies at our center with targeted investigational agents after autoSCT may improve results.

Disclosures: Khouri: Pfizer: Research Funding; Bristol Myers Squibb: Research Funding. Iyer: CRISPR: Research Funding; Spectrum: Research Funding; Daiichi Sankyo: Consultancy; Trillium: Research Funding; Curio Biosciences: Honoraria; Target Oncology: Honoraria; Afffimed: Research Funding; Merck: Research Funding; Legend Biotech: Consultancy; Rhizen: Research Funding; Seattle Genetics, Inc.: Research Funding. Popat: Bayer: Research Funding; Novartis: Research Funding. Qazilbash: Angiocrine: Research Funding; Amgen: Research Funding; Bioclinica: Consultancy; Janssen: Research Funding; Bioline: Research Funding. Champlin: DKMS America: Membership on an entity's Board of Directors or advisory committees; Actinium: Consultancy; Johnson and Johnson: Consultancy; Omeros: Consultancy; Cytonus: Consultancy; Takeda: Patents & Royalties; Genzyme: Speakers Bureau.

*signifies non-member of ASH