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4028 Characteristics, Treatment Patterns, and Outcomes in Primary Cutaneous Gamma Delta T Cell Lymphoma (PCGDTCL): A Real World Multi-Institutional Analysis of a Rare Malignancy

Program: Oral and Poster Abstracts
Session: 624. Hodgkin Lymphoma and T/NK Cell Lymphoma—Clinical Studies: Poster III
Hematology Disease Topics & Pathways:
Diseases, Lymphoma (any), T-Cell Lymphoma, Lymphoid Malignancies
Monday, December 9, 2019, 6:00 PM-8:00 PM
Hall B, Level 2 (Orange County Convention Center)

Kevin A. David, MD1, Melissa Pulitzer, MD2*, Joan Guitart, MD3*, Maria Estela Martinez-Escala, MD3*, Shamir Geller, MD4*, Yaqun Wang1*, N. Nora Bennani, MD5, Kay M. Ristow, BS5*, Daniel J. Landsburg, MD6,7, Nicole Winchell8*, Paul Haun, MD9*, Pamela Allen, MD, MSc10, Basem M. William, MRCP, MD11, Nathan Denlinger, MS, DO12, Neha Mehta-Shah, MD13, Ryan A. Wilcox, MD14, Alexandra Hristov14*, Tatyana A. Feldman, MD15, Alex Weller16*, Andrew M. Evens, DO, MSc1 and Steven M. Horwitz, MD17

1Rutgers Cancer Institute of New Jersey, New Brunswick, NJ
2Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY
3Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL
4Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
5Division of Hematology, Mayo Clinic, Rochester, MN
6Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA
7Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA
8Lymphoma Program, University of Pennsylvania, Philadelphia, PA
9Department of Dermatology, University of Pennsylvania, Philadelphia, PA
10Emory University Winship Cancer Institute, Decatur, GA
11The Ohio State University James Comprehensive Cancer Center, Columbus, OH
12Ohio State University Wexner Medical Center, Columbus, OH
13Department of Medicine, Division of Oncology, Washington University, Olivette, MO
14University of Michigan, Ann Arbor, MI
15Hackensack University Medical Center, NY, NY
16Hackensack University Medical Center, Hackensack, NJ
17Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY

Background: PCGTCL is a rare disorder, accounting for < 1% of all lymphomas. In part given the rarity, timely and accurate diagnosis (dx) remains challenging. Moreover, PCGTCL is typically characterized by a highly aggressive course. We conducted a multi-institutional, retrospective analysis to delineate pathology, patient (pt) characteristics, treatment patterns & outcomes of PCGDTCL in the modern era.
Methods: We collected detailed information on pts with PCGDTCL dx between 2000 - 2017 across 10 academic centers. Pathologic data, including IHC & flow characteristics on de-identified pathology reports, were reviewed centrally by an expert dermatopathologist (MP). A pathologic tier was assigned to each case based on fidelity to the following pre-defined minimum criteria: flow cytometric evidence of gamma and/or delta protein-expressing lymphoma or histopathologic evidence of gamma and/or delta protein expression & at least 50% atypical lymphocytes positive for gamma/delta immunostain (IHC) with tissue representative of entire lesion. The presence of >25% CD30 positivity of malignant lymphocytes was an exclusion criterion. Further, PCR evidence of TCR gamma monoclonality or TCR beta/betaF1 negativity alone were inadequate for inclusion with confirmation of gamma/delta phenotype (especially IHC) being key for inclusion. A clinical tier was also assigned to each case based on group consensus. A composite score was derived by combining pathologic & clinical tiers, with those fitting a pre-determined score threshold included in the primary analysis. Univariate (UVA) associations were derived via Cox model for associations with survival.
Results: Collectively, all centers submitted a total of 80 cases that were dx & treated locally as PCGDTCL. 48 (60%) cases met pre-defined criteria for inclusion of bona fide dx of PCGTCL. 26 (33%) cases had insufficient composite scores and were grouped in a 2nd tier & 6 cases had incomplete follow-up data and were unsuitable for analysis. The most common reason for placement in the 2nd tier was negativity for gamma/delta IHC or lack of documentation of such testing (n=16). Among the top tier of 48 veritable cases, 32 pts (67%) were male, 39 (81%) white & 4 (8%) black. Median age was 62 years (range 20-88). 19 (40%) pts had B symptoms at dx; ECOG performance status (PS) 0 in 12 pts (25%) & 1-3 in 22 cases (45%) (unknown 29%); anemia was present in 21 pts (44%) & LDH increased in 22 (46%). Bone marrow was involved in only 3 pts (6%) & hemophagocytic syndrome was present at dx in 6 pts (12%). Frontline therapy was heterogeneous (Table 1) with the most common therapies being bexarotene alone in 8 pts; UV therapy in 6 pts; and CHOP in 4 pts. Furthermore, there was inclusion of etoposide in 12 pts (25%), anthracyclines in 9 (19%) & platinum agents in 3 pts (6%). The overall response to 1st line therapy was 40% (19% complete response) with stable disease in 10%, progression in 35% & unknown in 15%. Seven pts (15%) received consolidative stem cell transplantation (SCT), which was allogeneic in all but 1 case. The 2-year PFS for the 48 bona fide pts was 39% (95% CI 0.26-0.59) (Fig 1A) & 2-year OS was 36% (95% CI 0.23-.56) (Fig 1B). The 26 cases in the 2nd tier had overall similar 2-year PFS of 41% (95% CI 0.15-67) and OS of 37% (95% CI 0.22-0.62). In terms of impact of therapy, use of consolidative SCT in 1st remission was associated with improved survival (P=0.02) (Fig 1C). No other therapeutic variable had significance. In UVA for baseline factors, PS (P=0.006) (Fig 1D) and increased vs. normal LDH (P=0.05) were significantly associated with OS. Median OS for pts with normal LDH was 25 months vs 12 months with increased LDH. Median OS for pts with ECOG PS 0 was not reached vs approximately 14 months for ECOG PS 1-3.
Conclusions: To the best of our knowledge, this series represents one of the largest reported to date of PCGDTCL. Accurate diagnosis and classification of PCGDTCL need ongoing analysis and delineation. Using strict criteria, only 60% of cases across 10 academic centers were confirmed as bona fide PCGDTCL. Analysis of these pts treated in the modern era demonstrated modest survival. In addition, we identified several prognostic factors, in particular LDH and ECOG PS, associated with patient outcome. Furthermore, the incorporation of allogeneic SCT in 1st remission may contribute to improved long-term survival. Enhanced treatment options and continued collaboration are critically needed in this rare disease.

Disclosures: Bennani: Bristol-Myers Squibb: Research Funding; Seattle Genetics: Other: Advisory board; Adicet Bio: Other: Advisory board; Kite Pharma: Other: Advisory board; Kite Pharma: Other: Advisory board; Adicet Bio: Other: Advisory board; Adicet Bio: Other: Advisory board; Seattle Genetics: Other: Advisory board; Purdue Pharma: Other: Advisory board; Seattle Genetics: Other: Advisory board; Purdue Pharma: Other: Advisory board; Purdue Pharma: Other: Advisory board; Bristol-Myers Squibb: Research Funding; Bristol-Myers Squibb: Research Funding; Kite Pharma: Other: Advisory board. Landsburg: Curis, Inc: Consultancy, Research Funding; Takeda: Research Funding; Triphase: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Speakers Bureau; Morphosys: Membership on an entity's Board of Directors or advisory committees. Haun: Karger, Inc.: Other: Royalties: Textbook. William: Techspert: Consultancy; Guidepoint Global: Consultancy; Defined Health: Consultancy; Celgene Corporation: Consultancy; Kyowa Kirin, Inc.: Consultancy. Mehta-Shah: Celgene: Research Funding; Celgene: Research Funding; Roche/Genentech: Research Funding; Kiowa Hakka Kirin: Consultancy; Bristol Myers Squibb: Research Funding; Roche/Genentech: Research Funding; Verastem Pharmaceuticals: Research Funding; Bristol Myers Squibb: Research Funding; Innate Pharmaceuticals: Research Funding; Verastem Pharmaceuticals: Research Funding; Corvus Pharmaceuticals: Research Funding; Innate Pharmaceuticals: Research Funding; Corvus Pharmaceuticals: Research Funding. Wilcox: Bristol-Myers Squibb: Research Funding; Millenium/Takeda: Research Funding; CTI Biopharma: Research Funding; Incyte: Research Funding. Feldman: AbbVie: Honoraria, Other: Travel expenses, Speakers Bureau; Seattle Genetics: Consultancy, Honoraria, Other: Travel expenses, Speakers Bureau; Eisai: Research Funding; Kyowa Hakko Kirin: Research Funding; Celgene: Honoraria, Research Funding, Speakers Bureau; Takeda: Honoraria, Speakers Bureau; Pfizer: Research Funding; Portola Pharma: Research Funding; Roche: Research Funding; Trillium: Research Funding; Viracta: Research Funding; Roche: Research Funding; Pharmacyclics: Honoraria, Other: Travel expenses, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Cell Medica: Research Funding; Amgen: Research Funding; Bayer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Kite Pharma: Honoraria, Other: Travel expenses, Speakers Bureau; Corvus: Research Funding. Evens: Seattle Genetics: Consultancy, Honoraria, Research Funding; Pharmacyclics: Consultancy, Honoraria; Epizyme: Consultancy, Honoraria; Tesaro: Research Funding; MorphoSys: Consultancy, Honoraria; Takeda: Research Funding; Merck: Research Funding; Novartis: Consultancy, Honoraria. Horwitz: ADCT Therapeutics: Research Funding; Corvus Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astex: Consultancy; Affimed: Consultancy; Forty-Seven: Research Funding; Trillium: Research Funding; Mundipharma: Consultancy; Innate Pharma: Consultancy; Infinity/Verastem: Consultancy, Research Funding; Portola: Consultancy; Seattle Genetics: Consultancy, Research Funding; Kyowa Hakko Kirin: Consultancy; Celgene: Consultancy, Research Funding; Kura: Consultancy; Millennium/Takeda: Consultancy, Research Funding; Aileron: Research Funding; Miragen: Consultancy.

*signifies non-member of ASH