-Author name in bold denotes the presenting author
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Clinically Relevant Abstract denotes an abstract that is clinically relevant.

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4146 Outcomes of Follicular Lymphoma Patients Treated with Frontline Bendamustine and Rituximab: Impact of Histologic Grade and Early Progression on Overall Survival

Program: Oral and Poster Abstracts
Session: 623. Mantle Cell, Follicular, and Other Indolent B-Cell Lymphoma—Clinical Studies: Poster III
Hematology Disease Topics & Pathways:
Adult, Follicular Lymphoma, Diseases, Non-Hodgkin Lymphoma, Study Population, Lymphoid Malignancies
Monday, December 3, 2018, 6:00 PM-8:00 PM
Hall GH (San Diego Convention Center)

Allison M. Winter, MD1, Loretta J. Nastoupil, MD2, Melody R. Becnel, MD2, James R. Cerhan, MD, PhD3, Thomas M. Habermann, MD3, Brian K. Link, MD4, Matthew J. Maurer, MS3, Bita Fakhri, MD, MPH5, Prathima Reddy, MD6*, Stephen D. Smith, MD6, Dhruvika Mukhija, MD1*, Deepa Jagadeesh, MD, MPH1, Amrita Desai, MD7*, Juan Pablo Alderuccio, MD7, Izidore S. Lossos, MD8, Pooja Mehra, MD9*, Craig A. Portell, MD9, Christopher R. D'Angelo, MD10*, Vaishalee P. Kenkre, MD10, Max L. Goldman, MD11, Oscar Calzada, BS11*, Jonathon B. Cohen, MD, MS11, Mohammad Junaid Hussain, MD12, Nilanjan Ghosh, MD, PhD12, Yang Liu, MD13*, Stefan Klaus Barta, MD, MRCP, MS14, Paolo F Caimi, MD15, Adam Kittai, MD16, Alexey V Danilov, MD, PhD16, Timothy Tiutan, MD17*, Peter Martin, FRCPC, MD, MS17, Nathalie Danielson, MSN, RN, ACNP-BC18*, Manali Kamdar, MD19, Abhigna Kodali, MD20*, Andrew M. Evens, DO, MSc21, Brad S Kahl, MD5 and Brian T. Hill, MD, PhD22,23

1Taussig Cancer Institute, Department of Hematology & Medical Oncology, Cleveland Clinic, Cleveland, OH
2The University of Texas MD Anderson Cancer Center, Houston, TX
3Mayo Clinic, Rochester, MN
4Division of Hematology, Oncology, and Blood & Marrow Transplantation, University of Iowa, Iowa City, IA
5Division of Medical Oncology, Washington University School of Medicine, Saint Louis, MO
6Seattle Cancer Care Alliance, University of Washington, Seattle, WA
7Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL
8Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, FL
9Division of Hematology and Oncology, University of Virginia, Charlottesville, VA
10Division of Hematology/Oncology, University of Wisconsin, Madison, WI
11Winship Cancer Institute, Department of Hematology and Medical Oncology, Emory University, Atlanta, GA
12Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute, Carolinas Healthcare System, Charlotte, NC
13Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, PA
14Fox Chase Cancer Center, Philadelphia, PA
15Adult Hematologic Malignancies & Stem Cell Transplant Section, University Hospitals Seidman Cancer Center, Cleveland, OH
16Knight Cancer Institute, Oregon Health and Science University, Portland, OR
17Division of Hematology and Oncology, Weill Cornell Medical College-New York Presbyterian Hospital, New York, NY
18Vanderbilt-Ingram Cancer Center, Nashville, TN
19Department of Medicine, Division of Hematology, University of Colorado School of Medicine, Denver, CO
20Tufts University School of Medicine and Cancer Center, Boston, MA
21Rutgers Cancer Institute of New Jersey, New Brunswick, NJ
22Taussig Cancer Institute, Department of Hematology & Medical Oncology, Cleveland Clinic Foundation, Cleveland, OH
23Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH

Background: Bendamustine and rituximab (BR) is a commonly chosen frontline treatment for grade 1-2 (G 1-2) follicular lymphoma (FL). This regimen resulted in significantly longer progression-free survival (PFS) and less toxicity compared to R-CHOP in the STiL trial [Rummel et al., 2013] and similar results were observed when comparing BR vs. R-CHOP/R-CVP in the confirmatory BRIGHT trial [Flinn et al., 2014, updated ASCO 2017]. Importantly, patients (pts) with grade 3A (G 3A) FL were excluded from these studies, yet the conclusions are often extrapolated to the treatment of G 3A pts. Notably, G 3A pts were included in the GALLIUM trial which used both bendamustine as well as CHOP backbones. Several retrospective studies of FL pts treated with frontline R-CHOP have demonstrated equivalent or improved overall survival (OS) for G 3A relative to G 1-2 FL (Koch et al., 2016, Mustafa et al., 2017, Yuan et al., 2017, Maeshima et al., 2013). Early disease progression after diagnosis and treatment with frontline R-CHOP has been identified as a strong predictor of poor OS in FL pts [Casulo et al. 2015], but has not been assessed in pts treated with frontline BR. We retrospectively evaluated outcomes of a large cohort of FL pts treated with frontline BR and stratified the results based on histologic grade and early vs. late progression.

Methods: We reviewed medical records of adult (age >18) pts with FL treated with frontline BR at 18 US cancer centers. There was no central pathology review; each academic institution confirmed the diagnosis and grade of FL. Pts with unknown grade, grade 3B, or cutaneous FL were excluded. Baseline characteristics between grades were evaluated with the Chi-Square test for categorical variables and the Mann-Whitney U for continuous variables. Outcomes were calculated from time of initiation of BR. Patients were grouped according to whether or not they had progression of disease within 24 months of BR initiation (POD24). OS and PFS were estimated using the Kaplan-Meier method and compared using the log-rank test.

Results: 687 pts were included (616 G 1-2, 71 G 3A). Median age at diagnosis was 60 years (range 21-94) with 53% men. The median time from diagnosis to treatment with BR was 1 month (range 0-139). The median duration of follow up for the entire cohort was 39 months. Characteristics including age, gender, ethnicity, ECOG, stage, LDH, and FLIPI are shown in the Table, and did not significantly differ between G 1-2 and G 3A pts. Rates of complete response (CR) and partial response (PR) to BR were similar between G 1-2 and G 3A (72%/22% vs. 66%/21%, respectively, p=0.114) but progressive disease (PD) was higher in G 3A pts (11.9%) relative to G 1-2 (4.8%, p=0.025). As shown in the Figure (A and B), 3-year PFS and OS was significantly longer for G 1-2 vs. G 3A pts (75% vs. 65%, log rank p= 0.035 and 90% vs. 86%, log rank p=0.007, respectively). Seventy-six (12.3%) of the 616 G 1-2 pts and 13 (18.3%) of the 71 G 3A pts experienced POD24 (p=0.19). For pts with both G 1-2 and G 3A FL, POD24 was associated with inferior OS (3-year OS 95% vs. 57% for G 1-2 pts, log rank p<0.0001 and 3-year OS 93% vs. 37% for G 3A pts, log rank p<0.0001) compared to patients without POD24.

Conclusions: G 3A FL pts have an inferior OS and are significantly more likely to have PD to frontline BR compared to G 1-2, which differs from the published experience with R-CHOP. Similar to outcomes after frontline treatment with R-CHOP, POD24 after frontline BR for FL is associated with very poor OS. Future studies are needed to address optimal frontline management of pts with G3A as well as for pts with any grade FL with POD24 after frontline BR.

Disclosures: Nastoupil: Novartis: Honoraria; Genentech: Honoraria, Research Funding; Gilead: Honoraria; Celgene: Honoraria, Research Funding; TG Therappeutics: Research Funding; Karus: Research Funding; Merck: Honoraria, Research Funding; Spectrum: Honoraria; Janssen: Research Funding; Juno: Honoraria. Cerhan: Celgene: Research Funding; Nanostring: Research Funding; Jannsen: Other: Scientific Advisory Board. Maurer: Celgene: Research Funding; Nanostring: Research Funding; Morphosys: Research Funding. Smith: Genentech: Research Funding; Incyte Corporation: Research Funding; Portola Pharmaceuticals: Research Funding; Pharmacyclics: Research Funding; Merck Sharp and Dohme Corp.: Consultancy, Research Funding; Acerta Pharma BV: Research Funding; Seattle Genetics: Research Funding. Lossos: Affimed: Research Funding. Portell: TG therapeutics: Research Funding; Amgen: Consultancy; Kite: Research Funding; AbbVie: Research Funding; BeiGene: Research Funding; Acerta: Research Funding; Genentech/Roche: Consultancy, Research Funding; Infinity: Research Funding. Calzada: Seattle Genetics: Research Funding. Cohen: Bristol-Myers Squibb: Research Funding; Infinity Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Infinity Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Millennium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; Bristol-Myers Squibb: Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BioInvent: Consultancy; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Research Funding; BioInvent: Consultancy. Ghosh: Celgene: Consultancy, Honoraria; Pharmacyclics, an Abbvie Company: Consultancy, Honoraria, Research Funding, Speakers Bureau; Abbvie: Honoraria, Speakers Bureau; SGN: Consultancy, Honoraria, Research Funding, Speakers Bureau; Juno: Consultancy, Honoraria, Research Funding; Gilead: Consultancy, Honoraria, Speakers Bureau; F. Hoffman-La Roche Ltd: Research Funding; Forty seven Inc: Research Funding; Spectrum: Consultancy, Honoraria; Genentech: Research Funding; TG Therapeutics: Consultancy, Honoraria, Research Funding. Barta: Janssen: Membership on an entity's Board of Directors or advisory committees; Merck, Takeda, Celgene, Seattle Genetics, Bayer: Research Funding; Curis: Other: Travel support. Caimi: Kite Pharma: Other: Advisory Board Participation; Genentech: Other: Advisory Board PArticipation, Research Funding; Celgene: Speakers Bureau; Kite Pharma: Other: Advisory Board Participation. Danilov: Gilead Sciences: Consultancy, Research Funding; Aptose Biosciences: Research Funding; Bayer Oncology: Consultancy, Research Funding; Astra Zeneca: Consultancy; Genentech: Consultancy, Research Funding; Takeda Oncology: Research Funding; TG Therapeutics: Consultancy; Verastem: Consultancy, Research Funding. Martin: AstraZeneca: Consultancy; Seattle Genetics: Consultancy; Janssen: Consultancy; Kite: Consultancy; Gilead: Consultancy; Bayer: Consultancy. Kamdar: Seattle Genetics: Speakers Bureau; Genentech: Consultancy. Kahl: AstraZeneca: Consultancy; Acerta: Consultancy; Juno: Consultancy; CTI: Consultancy; Celgene: Consultancy; Gilead: Consultancy; Seattle Genetics: Consultancy; Abbvie: Consultancy; Genentech: Consultancy; ADC Therapeutics: Consultancy. Hill: Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees.

*signifies non-member of ASH