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4110 Feasibility and Benefit of Molecularly-Informed Enrollment into Early Phase Clinical Trials for Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma

Program: Oral and Poster Abstracts
Session: 621. Lymphoma—Genetic/Epigenetic Biology: Poster III
Hematology Disease Topics & Pathways:
Adult, Diseases, Technology and Procedures, B-Cell Lymphoma, Study Population, Clinically relevant, Lymphoid Malignancies, Quality Improvement , genetic profiling, molecular testing
Monday, December 3, 2018, 6:00 PM-8:00 PM
Hall GH (San Diego Convention Center)

Jean-Marie Michot, MD1*, Valérie Camara-clayette2*, Audrey Detolle3*, Claude Chahine, MD4*, Julien Lazarovici, MD5*, Alina Danu, MD4*, Jacques Bosq6*, David Ghez, MD, PhD7*, Peggy Dartigues-Cuillères, MD6*, Julia Arfi-Rouche6*, Rastilav Bahleda6*, Wassila Rahali6*, Andrea Varga8*, Capucine Baldini8*, Lambros Tselikas6*, Clélia Paume6*, Helene Lecourt6*, Sophie Cotteret6*, Veronique Vergé6*, Jean-Charles Soria6*, Christophe Massard8* and Vincent Ribrag, MD9

1Institut Gustave Roussy, Villejuif, France
2Hematological transfert Laboratory, Gustave Roussy, Villejuif, France
3Drug Development Department, Gustave Roussy, Villejuif, France
4Department of Hematology, Gustave Roussy Cancer Campus, Villejuif, France
5Department of Hematology, Institute Gustave Roussy, Villejuif, France
6Gustave Roussy, Villejuif, France
7Department of Hematology, Gustave Roussy Cancer Center, Villejuif, France
8Gustave Roussy Cancer Campus, Villejuif, France
9DITEP, Gustave Roussy, Université Paris-Saclay, Villejuif, France

Background: Patients with relapsed or refractory diffuse large B cell lymphoma (r/r DLBCL) often do poorly with conventional salvage regimens of chemotherapy. Next-generation sequencing (NGS) panels can rapidly identify recurrent molecular abnormalities, thus helping to orient patients (pts) in appropriate targeted therapies or clinical trials. We aimed to evaluate whether selecting pts through tumor genotyping is associated with a better outcome.

Methods: From 2013 to 2018, all pts with r/r DLBCL having molecular portrait of tumor before enrollment in early clinical trials (eaCTs) for r/r DLBCL were analyzed for clinical and histomolecular characteristics, tumor response, progression-free survival (PFS) duration of response and overall survival. The objective were to evaluate the feasibility and potential benefit of using tumor genotyping for guiding enrollment in eaCTs. Molecular screening methods included immunohistochemistry, PCR-based assays and next-generation sequencing. All pts gave their written consent for the study.

Results: Sixty-two pts with r/r DLBCL had tumor molecular portraits. At the time of tumor molecular portrait, the median age was 69 years (range 26-77), median of previous line of therapies was 2 (range 1-9) and 14 pts (23%) had prior received auto stem-cell transplant. Fifteen out of the 62 pts (24%) were molecularly oriented (MO) in eaCTs. Identification of potentially actionable targets was found in 30/62 (48%) of pts, of whom 15/30 (50%) received a molecularly-informed therapy. Beyond molecular portrait, fifty pts were enrolled in eaCTs (15 pts were MO and 35 were non-MO oriented) and 12 pts were not enrolled in eaCTs. The MO-oriented group included the following therapeutic targets: CD79A/B or MYD88 (n=10 pts), EZH2 or ARIDI1A (n=3 pts), MYC (n=1 pt) and BRAF (n=1 pt). The overall responses rate was 60% (6 PR and 3 CR) in MO group versus 23% (5 PR and 2 CR) in non-MO group (p= 0.01). The median of PFS in MO and non-MO groups were 2.2 months and 1.9 months, respectively (p=0.23; HR=0.69 [CI95:0.38-1.26]). The median duration of response in MO and non-MO groups were 10.9 and 9.3 months, respectively (p=0.78; HR=0.76 [CI95: 0.26-2.18]. The mean PF2/PF1 ratio in MO and non-MO groups were 2.34 [CI95: 0.27-4.41] and 1.67 [CI:0.53-2.81], respectively (p=0.093; HR=0.61 [CI95: 0.33-1.14]. The median overall survival in MO and non-MO groups were 8.9 and 7.7 months, respectively (p=0.34; HR=0.69 [CI95: 0.33-1.47]).

Conclusions: Molecularly oriented treatments of recurrent diffuse large B-cell lymphoma demonstrates higher responses rates. A subset of patients with recurrent or refractory diffuse large B-cell lymphoma may benefit from incorporation of tumor genotyping to guide their enrollment in clinical trials. Accelerating the use of prospective genomics tumor molecular portraits may increase the chances for a precision medicine for recurrent diffuse large B-cell lymphoma.

Disclosures: Michot: Aduro: Other: Principal/sub-Investigator of Clinical Trials ; Eos: Other: Principal/sub-Investigator of Clinical Trials ; Nektar Therapeutics: Other: Principal/sub-Investigator of Clinical Trials ; Boeringer Ingleheim: Other: Principal/sub-Investigator of Clinical Trials ; Merus: Other: Principal/sub-Investigator of Clinical Trials ; Chugai: Other: Principal/sub-Investigator of Clinical Trials ; Pharmamar: Other: Principal/sub-Investigator of Clinical Trials ; Exelixis: Other: Principal/sub-Investigator of Clinical Trials ; BMS: Honoraria, Other: Principal/sub-Investigator of Clinical Trials & Non-Financial Support; Servier: Other: Principal/sub-Investigator of Clinical Trials ; Eisai: Other: Principal/sub-Investigator of Clinical Trials ; Pierre Farbe: Other: Principal/sub-Investigator of Clinical Trials ; Beigene: Other: Principal/sub-Investigator of Clinical Trials ; Clovis: Other: Principal/sub-Investigator of Clinical Trials ; Agios: Other: Principal/sub-Investigator of Clinical Trials ; Novartis: Other: Principal/sub-Investigator of Clinical Trials & Non-Financial Support; Menarini: Other: Principal/sub-Investigator of Clinical Trials ; Taiho: Other: Principal/sub-Investigator of Clinical Trials ; Rohe: Other: Principal/sub-Investigator of Clinical Trials & Non- Financial support; Abbvie: Other: Principal/sub-Investigator of Clinical Trials ; Oncoethix: Other: Principal/sub-Investigator of Clinical Trials ; Oncopeptides AB: Other: Principal/sub-Investigator of Clinical Trials ; Lilly: Other: Principal/sub-Investigator of Clinical Trials ; Gilead: Other: Non-Financial Support; Octimet: Other: Principal/sub-Investigator of Clinical Trials ; Forma: Other: Principal/sub-Investigator of Clinical Trials ; Xencor: Other: Principal/sub-Investigator of Clinical Trials ; Nanobiotix: Other: Principal/sub-Investigator of Clinical Trials ; Sanofi: Other: Principal/sub-Investigator of Clinical Trials ; MSD: Other: Principal/sub-Investigator of Clinical Trials ; Kyowa: Other: Principal/sub-Investigator of Clinical Trials ; Orion: Other: Principal/sub-Investigator of Clinical Trials ; Debiopharm: Other: Principal/sub-Investigator of Clinical Trials ; Daiichi Sankyo: Other: Principal/sub-Investigator of Clinical Trials ; Kura Oncology: Other: Principal/sub-Investigator of Clinical Trials ; Sierra Oncology: Other: Principal/sub-Investigator of Clinical Trials ; Takeda: Other: Principal/sub-Investigator of Clinical Trials ; Tesaro: Other: Principal/sub-Investigator of Clinical Trials ; Bayer: Other: Principal/sub-Investigator of Clinical Trials ; Aveo Pharmaceuticals: Other: Principal/sub-Investigator of Clinical Trials ; Astra-Zenenca: Honoraria, Other: Principal/sub-Investigator of Clinical Trials & Non-financial support; Astex: Other: Principal/sub-Investigator of Clinical Trials ; Argen-X: Other: Principal/sub-Investigator of Clinical Trials ; Amgen: Other: Principal/sub-Investigator of Clinical Trials ; Pfizer: Other: Principal/sub-Investigator of Clinical Trials ; Blueprint: Other: Principal/sub-Investigator of Clinical Trials ; Celgene: Other: Principal/sub-Investigator of Clinical Trials & Non-Financial Support; Loxo: Other: Principal/sub-Investigator of Clinical Trials ; Lysarc: Other: Principal/sub-Investigator of Clinical Trials ; Lytix Biopharma: Other: Principal/sub-Investigator of Clinical Trials ; Medimmune: Other: Principal/sub-Investigator of Clinical Trials ; Janssen: Honoraria, Other: Principal/sub-Investigator of Clinical Trials ; Innate Pharma: Other: Principal/sub-Investigator of Clinical Trials ; Incyte: Other: Principal/sub-Investigator of Clinical Trials ; H3 Biomedecine: Other: Principal/sub-Investigator of Clinical Trials ; GSK: Other: Principal/sub-Investigator of Clinical Trials ; Gortec: Other: Principal/sub-Investigator of Clinical Trials ; Genentech: Other: Principal/sub-Investigator of Clinical Trials ; Gamamabs: Other: Principal/sub-Investigator of Clinical Trials . Soria: Medimmune: Employment. Ribrag: BMS: Consultancy, Honoraria, Other: travel; Infinity: Consultancy, Honoraria; MSD: Honoraria; NanoString Technologies: Consultancy, Honoraria; argenX: Research Funding; epizyme: Consultancy, Honoraria; Incyte Corporation: Consultancy; pharmamar: Other: travel; Servier: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Roche: Honoraria, Other: travel; Amgen: Research Funding.

*signifies non-member of ASH