Response Of Rare Variants Of Cutaneous T Cell Lymphoma (CTCL) To Treatment With Bexarotene. A Prospective German DeCOG Trial
Authors: Weichenthal Michael , Goldinger Simone , Wehkamp Ulrike , Beyer Marc , Stein Annette , Tsianakas Athanasios , Koch André , Yazdi Amir , Wobser Marion , Frambach Yvonne , Dippel Edgar , Geißler Eva-Maria , Loquai Carmen , Kurschat Peter , Pföhler Claudia , Hartmann Anke , Coors Esther , Hallermann Christian , Mohr Peter , Hillen Uwe , Belloni Benedetta , Vogel Sandra , Mitteldorf Christina , Assaf Chalid , Klemke Claus-Detlev , Becker Juergen C , Dummer Reinhard , Nicolay Jan 
Published: October 2019

Abstract

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.