alitretinoin and Lymphoma--T-Cell--Cutaneous

In this survey, we analyzed data from patients suffering from the most common cutaneous T-cell lymphomas (CTCLs) subtypes mycosis fungoides (MF) and Sézary syndrome (SS), treated with the retinoid alitretinoin during a 7-year period at our outpatient department between 2015 and 2020.. We analyzed patient medical records including TNMB stage, side effects under therapy with alitretinoin, time to next treatment (TTNT), and previous photo documentation.. A total of 35 patients with MF (n = 28) and SS (n = 7) were included in the study, of whom 69% were male and 31% were female. The mean age of onset was 56 ± 15 years in MF and 65.4 ± 10.8 years in SS with 51.4% having early stage (IA-IIA) and 48.6% having advanced stage (IIB-IVA) CTCL. Of these patients 37.2% responded to alitretinoin, 28.6% had a stable course, and 34.3% experienced progression. Alitretinoin was administered as a monotherapy (25.7%) or combined with five concomitant therapies (74.2%), most frequently with ECP (31.4%) and PUVA (11.4%). 63% did not report any side effects, most often hypertriglyceridemia (20%) was described.. Considering that nearly two thirds of the CTCL patients treated with alitretinoin showed a response or stable disease, together with a low number of side effects and low cost compared to bexarotene, alitretinoin may be a potential alternative in the treatment of less advanced CTCLs. This survey represents the largest number of recorded therapies with the retinoid alitretinoin in CTCLs in a European patient collective.

Topics: Adult; Aged; Alitretinoin; Antineoplastic Agents; Bexarotene; Combined Modality Therapy; Disease Progression; Female; Humans; Lymphoma, T-Cell, Cutaneous; Male; Middle Aged; Mycosis Fungoides; PUVA Therapy; Sezary Syndrome; Skin Neoplasms

The vitamin A derivative 9-cis-retinoic acid (9-cis-RA) has been used for the treatment and prevention of cutaneous T-cell lymphoma (CTCL). However, the precise mechanism by which 9-cis-RA treatment ameliorates CTCL remains elusive. Our research shows that 9-cis-RA inhibits proliferation and induces apoptosis in CTCL cells in a dose-dependent and time-dependent manner. 9-Cis-RA also induced G0/G1 cell cycle arrest by downregulation of cyclin D1. We confirmed that 9-cis-RA significantly decreased phosphorylation of JAK1, STAT3, and STAT5 and downregulated Bcl-xL and cyclin D1, indicating that 9-cis-RA inhibited the activation of JAK/STAT signaling. Meanwhile, 9-cis-RA also activated classical RA-mediated transcription by retinoic acid receptors (RAR) and/or retinoid X receptors (RXR) in a CTCL cell line. Thus, 9-cis-RA may be effective for chemotherapy and may prevent human CTCL by inhibiting proliferation and inducing apoptosis by inhibition of the JAK/STAT pathway and activation of the RAR/RXR pathway.

Topics: Alitretinoin; Antineoplastic Agents; Apoptosis; Cell Proliferation; Down-Regulation; G1 Phase Cell Cycle Checkpoints; Humans; Janus Kinases; Lymphoma, T-Cell, Cutaneous; Nitriles; Pyrazoles; Pyrimidines; Receptors, Retinoic Acid; Resting Phase, Cell Cycle; RNA, Messenger; Skin Neoplasms; STAT Transcription Factors

Topics: Alitretinoin; Antineoplastic Agents; Gels; Humans; Lymphoma, T-Cell, Cutaneous; Male; Middle Aged; Skin Neoplasms; Tretinoin