THERAKOS® Photopheresis
What Is THERAKOS Photopheresis?
The THERAKOS® Photopheresis System is an immunomodulatory therapy that uses extracorporeal photopheresis (ECP) to help enhance immunologic response.* THERAKOS Photopheresis was first approved by the FDA in 1987 for the palliative treatment of CTCL skin symptoms in patients who were not responsive to other types of treatment.1,2
Since launch over 35 years ago, there have been over 1.3 million THERAKOS Photopheresis treatments performed (worldwide).3 THERAKOS Photopheresis is now available in approximately 170 treatment centers across the United States. Treatment centers are independent, third-party facilities not owned, operated, or controlled by Mallinckrodt Pharmaceuticals.
*While the exact mechanism of action continues to be investigated, THERAKOS® Photopheresis exhibits anticlonal cytotoxic characteristics in the treatment of CTCL skin manifestations and enhances the immunologic response to skin manifestations of the disease.1
1. UVADEX (methoxsalen) Sterile Solution (prescribing information). Therakos, Inc. 2. Food and Drug Administration. Premarket approval: UVAR Photopheresis System. Accessed August 2, 2024. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?id=P860003 3. Data on file. Ref-07615. Mallinckrodt Pharmaceuticals.
THERAKOS® Photopheresis Procedure1,2
Harness the immune system in managing skin manifestations of CTCL
Addressing the immune system imbalance may target the underlying cause of skin symptoms2-5*
References
1. THERAKOS® CELLEX® Photopheresis System Operator’s Manual. 1470493_Rev06_EN-US. Mallinckrodt; 2020. 2. UVADEX (methoxsalen) Sterile Solution (prescribing information). Therakos, Inc. 3. Yoo EK, Rook AH, Elenitsas R, Gasparro FP, Vowels BR. Apoptosis induction by ultraviolet light A and photochemotherapy in cutaneous T-cell lymphoma: relevance to mechanism of therapeutic action. J Invest Dermatol. 1996;107(2):235-242. 4. Gerber A, Bohne M, Rasch J, Struy H, Ansorge S, GolInick H. Investigation of annexin V binding to lymphocytes after extracorporeaI photoimmunotherapy as an early marker of apoptosis. Dermatology. 2000;201(2):111-117. 5. Hwang ST, Janik JE, Jaffe ES, Wilson WH. Mycosis fungoides and Sézary syndrome. Lancet. 2008;371(9616):945-957.
A Systemic Treatment Option
Skin symptoms of mycosis fungoides, the most common subtype of CTCL, typically have a long, indolent course.5,6 Patients may experience a long series of different treatments.
Treatment decisions can incorporate the disease stage, overall prognosis, patient quality of life, and most bothersome symptoms, as well as treatment history and patient preference.7
Some systemic treatment options for CTCL skin manifestations6:
When it’s time for systemic therapy, consider one that makes sense for patients in the middle of a long series of possible treatments.5,8
Potential Mechanism of Action*
-
Blood is fractionated via centrifugation. The “buffy coat” (the fraction containing the majority of leukocytes and platelets) is isolated and the remaining blood returned to the patient1
-
The buffy coat is treated with UVADEX® (methoxsalen) and then exposed to UVA light1
-
UVA activation of methoxsalen triggers cell death2,3,7-9
-
The buffy coat, containing living, dead, or dying cells; subcellular fragments; and soluble factors, is released back into the patient’s bloodstream2,9-13
-
The treated leukocytes are engulfed by phagocytic cells, leading to a range of indirect downstream immunomodulatory effects7,8,11,14,15
*The exact mechanism of action of UVADEX is not known.
Extracorporeal photopheresis (ECP) induces cell death in treated cells, which in turn initiates a cascade of immunomodulatory activities involving regulation of important immune cells and cytokines2,7-9,11,14,15
While the exact mechanism of action continues to be investigated, THERAKOS® Photopheresis exhibits anticlonal cytotoxic characteristics in the treatment of CTCL skin manifestations and enhances the immunologic response to skin manifestations of the disease16,17
- THERAKOS Photopheresis may induce an immunomodulatory effect against CTCL skin manifestations
- ECP inhibits DNA synthesis and cell division, inducing cell death in treated leukocytes, including CTCL cells2-4
References
1. THERAKOS® CELLEX® Photopheresis System Operator’s Manual. 1470493_Rev06_EN-US. Mallinckrodt; 2020. 2. UVADEX (methoxsalen) Sterile Solution (prescribing information). Therakos Inc. 3. Yoo EK, Rook AH, Elenitsas R, Gasparro FP, Vowels BR. Apoptosis induction by ultraviolet light A and photochemotherapy in cutaneous T-cell lymphoma: relevance to mechanism of therapeutic action. J Invest Dermatol. 1996;107(2):235-242. 4. Gerber A, Bohne M, Rasch J, Struy H, Ansorge S, GolInick H. Investigation of annexin V binding to lymphocytes after extracorporeaI photoimmunotherapy as an early marker of apoptosis. Dermatology. 2000;201(2):111-117. 5. Hwang ST, Janik JE, Jaffe ES, Wilson WH. Mycosis fungoides and Sézary syndrome. Lancet. 2008;371(9616):945-957. 6. Caffieri S, Di Lisa F, Bolesani F, et al. The mitochondrial effects of novel apoptogenic molecules generated by psoralen photolysis as a crucial mechanism in PUVA therapy. Blood. 2007;109(11):4988-4994. 7. Knobler R, Arenberger P, Arun A, et al. European dermatology forum – updated guidelines on the use of extracorporeal photopheresis 2020 – part 1. J Eur Acad Dermatol Venereol. 2020;34(12):2693-2716. 8. Hart JW, Shiue LH, Shpall EJ, Alousi AM. Extracorporeal photopheresis in the treatment of graft-versus-host disease: evidence and opinion. Ther Adv Hematol. 2013;4:320-334. 9. Craciun LI, Stordeur P, Schandené L, et al. Increased production of interleukin-10 and interleukin-1 receptor antagonist after extracorporeal photochemotherapy in chronic graft-versus-host disease. Transplantation. 2002;74:995-1000. 10. Caruso S, Poon IKH. Apoptotic cell-derived extracellular vesicles: more than just debris. Front Immunol. 2018;9:1486. 11. Tatsuno K, Yamazaki T, Hanlon D, et al. Extracorporeal photochemotherapy induces bona fide immunogenic cell death. Cell Death Dis. 2019;10:578. 12. Medina CB, Ravichandran KS. Do not let death us do part: 'find-me' signals in communication between dying cells and the phagocytes. Cell Death Differ. 2016;23(6):979-989. 13. Bisaccia E, Vonderheid EC, Geskin L. Safety of a new, single, integrated, closed photopheresis system in patients with cutaneous T-cell lymphoma. Br J Dermatol. 2009;161(1):167-169. 14. Marshall SR. Technology insight: ECP for the treatment of GvHD—can we offer selective immune control without generalized immunosuppression? Nat Clin Pract Oncol. 2006;3(6):302-314. 15. Morelli AE, Larregina AT, Shufesky WJ, et al. Internalization of circulating apoptotic cells by splenic marginal zone dendritic cells: dependence on complement receptors and effect on cytokine production. 2003;101:611-620. 16. Vieyra-Garcia PA, Wolf P. Extracorporeal photopheresis: a case of immunotherapy ahead of its time. Tranfus Med Hemother. 2020;47:226-234. 17. Shiue LH, Alousi AM, Wei C, Hosing CM, Duvic M, Ni X. Augmentation of blood dendritic cells by extracorporeal photopheresis in patients with leukemic cutaneous T-cell lymphoma and graft-versus-host disease. J Invest Dermatol. 2013;133(8):2098-2100.