PMID- 37648672 OWN - NLM STAT- MEDLINE DCOM- 20231101 LR - 20231112 IS - 2473-9537 (Electronic) IS - 2473-9529 (Print) IS - 2473-9529 (Linking) VI - 7 IP - 21 DP - 2023 Nov 14 TI - International study of treatment efficacy in SS shows superiority of combination therapy and heterogeneity of treatment strategies. PG - 6639-6647 LID - 10.1182/bloodadvances.2023011041 [doi] AB - Despite increasing availability of therapies, patients with Sezary syndrome (SS) commonly endure multi-line treatment journeys, mostly with partial responses of short duration. Measuring clinical benefit is challenging; time-to-next-treatment (TTNT) provides a robust, objective measurement of efficacy. This international observational study examines patterns of clinical care and therapeutic benefit as measured by TTNT. TTNT was calculated for monotherapies and combination therapies, with consideration to treatment line. 178 patients with SS (73% de novo, 27% secondary) were included, receiving 721 lines of systemic therapy, with median follow-up of 56.9 months. Across all lines, 58 different therapeutic regimens were prescribed (54 were systemic therapies) and classified into 17 treatment groups. The most common first-line treatments were extracorporeal photopheresis (ECP)-containing combination therapy (20%) and retinoid monotherapy (19%). Median TTNT for all first-line therapies was short (5.4 months). First-line, combination therapies had longer median TTNT than monotherapies, 10.0 vs 5.0 months (P = .004), respectively. Later delivery of combination therapies was associated with shorter clinical benefit, with median TTNT reduced to 6.2 and 2.2 months for mid-line (2nd-4th line) and late-line (>/=5th line), respectively (P < .001). First-line ECP-containing treatments were associated with longer median TTNT than non-ECP-containing treatments, 9.0 vs 4.9 months (P = .007). For both ECP-monotherapy and ECP-containing combination therapy, significant reductions in TTNT were seen in later lines. These data suggest therapeutic benefit from first-line delivery of combination therapy for SS and favor early inclusion of ECP in the treatment algorithm for those who can access it. CI - (c) 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved. FAU - Campbell, Belinda A AU - Campbell BA AUID- ORCID: 0000-0002-7316-8723 AD - Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia. AD - Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Australia. AD - Department of Clinical Pathology, The University of Melbourne, Parkville, Australia. FAU - Dobos, Gabor AU - Dobos G AUID- ORCID: 0000-0002-2544-7197 AD - Department of Dermatology, Hopital Saint Louis, Universite Paris Cite, Paris, France. AD - Department of Dermatology and Allergy, Charite - Universitatsmedizin Berlin, Corporate Member of Freie Universitat Berlin and Humboldt-Universitat zu Berlin, Berlin, Germany. FAU - Haider, Zahra AU - Haider Z AD - Department of Dermatology, Queen Elizabeth Hospital, Birmingham, United Kingdom. FAU - Prince, H Miles AU - Prince HM AUID- ORCID: 0000-0002-0058-2448 AD - Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Australia. AD - Department of Haematology, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne Australia. FAU - Bagot, Martine AU - Bagot M AUID- ORCID: 0000-0002-1631-5192 AD - Department of Dermatology, Hopital Saint Louis, Universite Paris Cite, Paris, France. FAU - Evison, Felicity AU - Evison F AD - Health Data Science Team, Research Development and Innovation, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom. FAU - van der Weyden, Carrie AU - van der Weyden C AUID- ORCID: 0000-0001-6655-9876 AD - Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Australia. AD - Department of Haematology, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne Australia. FAU - McCormack, Chris AU - McCormack C AD - Department of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia. AD - Department of Surgery, The University of Melbourne, Parkville, Australia. FAU - Ram-Wolff, Caroline AU - Ram-Wolff C AD - Department of Dermatology, Hopital Saint Louis, Universite Paris Cite, Paris, France. FAU - Miladi, Maryam AU - Miladi M AD - Department of Dermatology, Hopital Saint Louis, Universite Paris Cite, Paris, France. FAU - Scarisbrick, Julia J AU - Scarisbrick JJ AUID- ORCID: 0000-0002-8011-4408 AD - Department of Dermatology, University Hospital Birmingham, Birmingham, United Kingdom. LA - eng PT - Journal Article PT - Observational Study PL - United States TA - Blood Adv JT - Blood advances JID - 101698425 SB - IM MH - Humans MH - *Sezary Syndrome/drug therapy MH - *Skin Neoplasms/drug therapy MH - Treatment Outcome MH - Combined Modality Therapy MH - *Photopheresis PMC - PMC10628811 COIS- Conflict-of-interest disclosure: G.D. reports being on the advisory boards of Kyowa Kirin and Recordati Rare Diseases. H.M.P. is a member of advisory boards and receives honoraria from Kyowa Kirin, Mallinkrodt, Therakos, Innate Pharma, and Takeda. M.B. reports being on the advisory boards for Innate Pharma, Kyowa Kirin, Takeda, and Helsinn/Recordati. M.M. is a medical director and clinical trial investigator of Eurofins, BIO-EC (France). J.S. reports receiving consulting and/or honoraria from Takeda, Recordati, Helsinn, Kyowa Kirin, Mallinkrodt, Therakos, Affirmed. The remaining authors declare no competing financial interests. EDAT- 2023/08/31 00:41 MHDA- 2023/11/01 12:45 PMCR- 2023/09/01 CRDT- 2023/08/30 22:53 PHST- 2023/08/22 00:00 [accepted] PHST- 2023/06/23 00:00 [received] PHST- 2023/11/01 12:45 [medline] PHST- 2023/08/31 00:41 [pubmed] PHST- 2023/08/30 22:53 [entrez] PHST- 2023/09/01 00:00 [pmc-release] AID - 497698 [pii] AID - 10.1182/bloodadvances.2023011041 [doi] PST - ppublish SO - Blood Adv. 2023 Nov 14;7(21):6639-6647. doi: 10.1182/bloodadvances.2023011041.