ALBERT

Description: The Retinoid-X-Receptor specific retinoid bexarotene is approved for treatment of cutaneous T-cell lymphoma (CTCL) in the United States and Europe. CTCL is a heterogeneous group of peripheral non-Hodgkin lymphomas with different prognosis and different response to treatment and the current WHO classification contains nine different entities with Mycosis fungoides (MF) as the most common subtype. Since most data on efficacy and tolerability are available from studies with MF, this Dermatologic Cooperative Oncology Group (DeCOG) trial (ADO-CTCL-3) evaluates treatment response to bexarotene in patients with non-MF CTCL, encompassing CD30+ primary cutaneous ALCL and severe lymphomatoid papulosis (LyP), CD-30 negative pleomorphic TCL, Sezary's syndrome (SS), subcutaneous panniculitis-like TCL, and other defined variants. Additionally, patients with different rare variants of MF, including folliculotropic (fMF), granulomatous, erythrodermic, and CD30+ transformed MF were included. 200 patients with CTCL stage IB or higher and at least one prior treatment failure were registered in this trial with bexarotene at an initial daily dose of 150mg/m² orally und prophylactic fenofibrate medication. Bexatrotene was increased to a target dosage of 300 mg/m² in patients with tolarable serum lipids under these conditions. Patients were evaluated according to a standardized evaluation tool (tumor burden index; TBI) up to 24 weeks of of treatment or until progression occured. In responding patients, treatment could be continued until progression. After a central pathology board review process 2 patients needed to be excluded from evaluation because of misdiagnoses. Additional 11 patients could not be evaluated for response due to early withdrawal. Among the remaining patients there were 18 patients with SS, 8 cutaneous CD30+ ALCL, 10 Lyp, 9 other rare entities. In addition MF cases with folliculotropic subtype (18), CD30+ transformation (11), CD30- transformation (4), and a variety of other MF subtypes could be compared to the response in classical MF. Response to bexarotene could be confirmed in classical MF with an objective response (OR) rate of 37 percent (5% CR; 32% PR). Response rates for the other entities were as follows: CD30+ ALCL 50% OR, LyP 60% OR, SS 33% OR, other forms of CTCL together 33% OR. In MF with CD30+ transformation 46% responded, in contrast to only 11% of cases with folliculotropic MF. Tolerability was as expected with most grade III/IV toxicities limited to hyperlipidemia. Side effect management anf the incidence of serious adverse events could be substantially improved using standard algorithms for lipid control. In conclusion, this is one of the largest CTCL cohorts with exact pathological review worldwide evaluated for treatment response with bexarotene. Bexarotene appears to be a safe and effective treatment option also in non-classical MF and CTCL variants. Folliculotropic MF proved to be a difficult-to-treat entity and CD30 expression seems to be a favourable prognostic marker for treatment response. Disclosures: Weichenthal: Cephalon GmbH: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; TEVA GmbH: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding. Goldinger:Cephalon: Travel costs Other; TEVA: Travel costs, Travel costs Other. Wehkamp:TEVA GmbH: Travel costs Other. Beyer:TEVA GmbH: Honoraria, Research Funding; Cephalon GmbH: Honoraria, Research Funding. Stein:Cephalon: Travel costs Other; TEVA: Travel costs, Travel costs Other. Tsianakas:Cephalon: Travel costs Other; TEVA: Travel costs, Travel costs Other. Koch:Cephalon: Travel costs Other. Yazdi:Cephalon: Travel costs Other; TEVA: Travel costs, Travel costs Other. Wobser:Cephalon: Travel costs Other; TEVA: Travel costs, Travel costs Other. Frambach:Cephalon: Travel costs Other; TEVA: Travel costs, Travel costs Other. Dippel:Cephalon GmbH: Honoraria, Travel costs Other; TEVA GmbH: Honoraria, Travel costs, Travel costs Other. Geißler:Cephalon GmbH: Travel costs Other; TEVA GmbH: Travel costs, Travel costs Other. Loquai:TEVA GmbH: Travel costs Other. Kurschat:Cephalon: Travel costs Other; TEVA GmbH: Honoraria, Travel costs, Travel costs Other. Pföhler:Cephalon: Travel costs Other. Hartmann:Cephalon GmbH: Travel costs Other; TEVA GmbH: Travel costs, Travel costs Other. Coors:Cephalon GmbH: Travel costs Other; TEVA GmbH: Honoraria, Travel costs, Travel costs Other. Hallermann:TEVA GmbH: Travel costs Other. Mohr:TEVA: Honoraria, Travel costs Other. Hillen:TEVA: Travel costs Other. Belloni:Cephalon GmbH: Travel costs Other. Mitteldorf:Cephalon: Travel costs Other. Assaf:TEVA: Honoraria, Research Funding, Travel costs Other. Klemke:TEVA GmbH: Consultancy, Honoraria; Cephalon GmbH: Honoraria. Becker:Cephalon GmbH: Honoraria, Research Funding; TEVA GmbH: Honoraria. Dummer:Cephalon GmbH: Honoraria, Research Funding; TEVA GmbH: Honoraria. Nicolay:TEVA: Travel costs Other.

Description: Background: CTCL represents a rare group of non-Hodgkin lymphomas with substantial negative impact on patient (pt) quality of life and mortality in advanced-stage disease. Mycosis fungoides (MF), the most common subtype of CTCL, and the rarer leukemic variant Sézary syndrome (SS) are distinct subtypes of CTCL. Mogamulizumab is a first-in-class, defucosylated monoclonal antibody directed against C-C chemokine receptor 4 (CCR4), which is highly expressed on malignant T-cells in CTCL. Primary results from the MAVORIC study (data cut-off December 2016), a phase 3 trial comparing mogamulizumab to FDA-approved vorinostat in adults with relapsed/refractory MF/SS, showed mogamulizumab significantly prolonged median progression-free survival compared with vorinostat (7.7 vs 3.1 months, P351 d was defined as cut-off for long-term exposure. Baseline characteristics across exposure groups are shown in the Table. Significant trends were observed for baseline Eastern Cooperative Oncology Group performance status (ECOG PS; P=0.04), disease type (P=0.03), and blood involvement (defined as ≥B1 per Olsen et al J Clin Oncol 2011; P351 d of exposure to mogamulizumab were drug eruption (9/45 [20%]), thrombocytopenia (5/45 [11%]), stomatitis (4/45 [9%]), and anemia (4/45 [9%]). Conclusions: This follow-up analysis of the phase 3 MAVORIC study demonstrated mogamulizumab treatment of pts with MF/SS for approximately 1 year was not associated with an increased safety risk. Significant long-term clinical benefit was observed in pts with blood involvement at baseline, regardless of CCR4 expression status. A higher proportion of pts who had long-term (〉351 days) exposure attained confirmed global response versus those who had less exposure. Disclosures Bagot: Takeda: Membership on an entity's Board of Directors or advisory committees; Innate Pharma: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Kyowa Kirin: Membership on an entity's Board of Directors or advisory committees; Actelion: Membership on an entity's Board of Directors or advisory committees. Dalle:Kyowa Hakko Kirin Pharmaceutical: Research Funding. Sokol:Mallinckrodt Pharmaceuticals: Consultancy; Seattle Genetics: Consultancy; Spectrum Pharmaceuticals: Consultancy. Tsianakas:Kyowa Kirin: Research Funding. Musiek:Seattle Genetics: Honoraria; Kyowa Kirin: Honoraria; Actelion: Other: Scientific Advisory Committee . Ortiz-Romero:Innate Pharma: Consultancy; Takeda: Consultancy; MEDA: Research Funding; Actelion: Consultancy; 4SC: Consultancy. Poligone:Johnson and Johnson: Research Funding; Kyowa Hakko Kirin: Research Funding; Soligenix: Research Funding; Mallinckrodt: Speakers Bureau; Stemline Therapeutics: Honoraria; Seattle Genetics: Honoraria. Duvic:Clinical Care Options: Consultancy; Soligenix, Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Mallinckrddt Pharmaceuticals (formerly Therakos): Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Huron Consulting Group: Consultancy; Taiwan Liposome Company LTD: Consultancy; Rhizen Pharma: Research Funding; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Kyowa Hakko Kirin, Co: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Precision Oncology, LLC: Membership on an entity's Board of Directors or advisory committees; Eisai: Research Funding; UT MD Anderson Cancer Center: Employment; Dr. Reddy's Laboratories (A.K.A. Promius Pharma): Consultancy; Defined Health: Consultancy; Medivir AB: Membership on an entity's Board of Directors or advisory committees; Medscape: Other: Speaker/Preceptor; Guidepoint Global: Consultancy; Jonathan Wood & Associates: Other: Speaker; Celgene Corp: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Evidera, Inc.: Consultancy; Kiniksa Pharmaceuticals: Consultancy; MEDACorp: Consultancy; The Lynx Group: Consultancy; Spatz Foundation: Research Funding; Forty Seven, Inc.: Membership on an entity's Board of Directors or advisory committees; Shape: Research Funding; Aclaris Therapeutics Int'l Ltd.: Honoraria, Membership on an entity's Board of Directors or advisory committees; Cell Medica Inc.: Consultancy, Honoraria; Allos: Research Funding; American Council on Extracorporeal Photopheresis (ACE): Membership on an entity's Board of Directors or advisory committees; Concert Pharmaceuticals, Inc.: Consultancy; Millennium Pharmaceuticals, Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; MiRagen Therapeutics: Consultancy; Huya Bioscience Int'l: Consultancy; Array Biopharma: Consultancy, Honoraria; Oncoceuticals: Research Funding; Tetralogics: Research Funding. Elmets:NCI: Research Funding; Veterans Administration: Research Funding; California Wine Grape Association: Research Funding; Soligenix: Research Funding; Elorac: Research Funding; Leo Pharma: Other: Data and Safety Monitoring Board. Leoni:Kyowa Kirin: Employment. Dwyer:Kyowa Kirin: Employment. Sun:Kyowa Kirin: Employment. Nikonova:Kyowa Kirin: Employment. Kim:miRagen: Research Funding; Forty Seven Inc: Research Funding; Kyowa-Kirin-Pharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; Innate Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Horizon Pharma: Consultancy, Research Funding; Merck: Research Funding; Soligenix: Research Funding; Eisai: Membership on an entity's Board of Directors or advisory committees, Research Funding; Medivir: Membership on an entity's Board of Directors or advisory committees; Neumedicine: Consultancy, Research Funding; Portola: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Galderma: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Tetralogic: Research Funding.

Description: Introduction: Cutaneous T- cell lymphoma (CTCL) is a rare form of non-Hodgkin lymphoma. Patients with CTCL suffer reduced quality of life from intractable itching and recurrent infections. Advanced stages have a poor prognosis. Mogamulizumab (Moga) is a monoclonal antibody directed against chemokine receptor 4 (CCR4), which is overexpressed on malignant T-cells. In a Phase I-II study in CTCL, Moga demonstrated a tolerable safety profile with a 37% overall response rate (ORR). Based on these results, MAVORIC [NCT01728805], an open-label, multinational, randomized, Phase III study, was initiated to compare Moga to vorinostat (Vor) in previously treated CTCL. This study is the largest randomized trial and the first pivotal trial to use progression-free survival (PFS) as a primary endpoint in CTCL. Methods: Adult patients with histologically confirmed mycosis fungoides (MF) or Sézary syndrome (SS) who had failed ≥1 systemic therapy were enrolled, stratified by disease type (MF or SS) and stage (IB/II or III/IV), and randomized 1:1 to Moga 1.0 mg/kg (weekly for the first 4-week cycle and then every 2 weeks) or Vor (400 mg daily). Patients randomized to Vor could crossover to Moga upon progression or intolerable toxicity. The primary endpoint was investigator-assessed PFS in the randomized population using the global composite response (based on skin, blood, nodes and viscera) according to the ISCL/EORTC consensus guidelines. Sample size was calculated to provide 90% power to detect a 50% improvement in PFS. Key secondary endpoints included ORR, duration of response (DOR) and quality of life (QoL). Results: A total of 372 patients were randomized (Intent-to-Treat population) and had the following characteristics (Moga vs Vor): median age 63.5 yrs (25-101) vs 65.0 yrs (25-89); ECOG-PS 0-1, 184 (99%) vs 186 (100%); ECOG-PS 2, 2 (1%) vs 0; stage IB/IIA, 36 (19.4%) vs 49 (26.3%); stage IIB, 32 (17.2%) vs 23 (12.4%); stage III/IV, 118 (63.4%) vs 114 (61.3%); MF, 105 (56.5%) vs 99 (53.2%); SS, 81 (43.5%) vs 87 (46.8%). The median number of prior systemic treatments for both the Moga and Vor arms was 3. According to investigator assessment, treatment with Moga resulted in a significant improvement in PFS compared to Vor (HR 0.53 [95% CI: 0.41, 0.69], p