Cutaneous T-cell lymphoma

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Last updated on 2024-07-23:19 regimens on this page
21 variants on this page
=Guidelines=
Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.
==ESMO==
*2018: Willemze et al. Primary cutaneous lymphomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up EuroPMC
**2013: Willemze et al. Primary cutaneous lymphomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up EuroPMC
**2010: Willemze & Dreyling. Primary cutaneous lymphomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up EuroPMC
**2009: Willemze & Dreyling. Primary cutaneous lymphoma: ESMO clinical recommendations for diagnosis, treatment and follow-up EuroPMC
**2008: Dummer & Dreyling. Primary cutaneous lymphoma: ESMO clinical recommendations for diagnosis, treatment and follow-up EuroPMC
**2007: Dummer. Primary cutaneous lymphomas: ESMO clinical recommendations for diagnosis, treatment and follow-up EuroPMC
==NCCN==
*NCCN Guidelines - Primary Cutaneous Lymphomas
*NCCN Guidelines - T-cell Lymphomas
=Upfront therapy=
==Gemcitabine monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence	Efficacy
Marchi et al. 2005	2002-06 to 2004-02 	Phase 2 	ORR: 75%
====Targeted therapy====
*Gemcitabine (Gemzar) 1200 mg/m2 IV once per day on days 1, 8, 15
28-day cycle for 6 cycles
===References===
# Marchi E, Alinari L, Tani M, Stefoni V, Pimpinelli N, Berti E, Pagano L, Bernengo MG, Zaja F, Rupoli S, Pileri S, Baccarani M, Zinzani PL. Gemcitabine as frontline treatment for cutaneous T-cell lymphoma: phase II study of 32 patients. Cancer. 2005 Dec 1;104(11):2437-41. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
==PUVA==
PUVA: Psoralen & Ultra-Violet A
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Edelson et al. 1987 	Not reported 	Non-randomized (RT)	 	
Whittaker et al. 2012 (EORTC 21011)	2003-2010 	Phase 3 (C) 	PUVA & Bexarotene	Did not meet primary endpoint of ORR
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
====Antineoplastic therapy====
*Methoxsalen (Uvadex) 0.6 mg/kg PO once per day on days 1, 3, 5, given first, 2 hours prior to UVA
*Ultraviolet A (UVA) delivered three times per week, with an initial UVA dose at 70% of the minimal phototoxic dose (MPD)
7-day cycles
===References===
# Edelson R, Berger C, Gasparro F, Jegasothy B, Heald P, Wintroub B, Vonderheid E, Knobler R, Wolff K, Plewig G, McKiernan G, Christiansen I, Oster M, Honigsmann H, Wilford H, Kokoschka E, Rehle T, Perez M, Stingl G, Laroche L. Treatment of cutaneous T-cell lymphoma by extracorporeal photochemotherapy: preliminary results. N Engl J Med. 1987 Feb 5;316(6):297-303. link to original article EuroPMC
# EORTC 21011: Whittaker S, Ortiz P, Dummer R, Ranki A, Hasan B, Meulemans B, Gellrich S, Knobler R, Stadler R, Karrasch M. Efficacy and safety of bexarotene combined with psoralen-ultraviolet A (PUVA) compared with PUVA treatment alone in stage IB-IIA mycosis fungoides: final results from the EORTC Cutaneous Lymphoma Task Force phase III randomized clinical trial (NCT00056056). Br J Dermatol. 2012 Sep;167(3):678-87. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00056056
==Topical therapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Kaye et al. 1989	1979-1987 	Randomized, >20 pts (C)	CAV-E & RT	Did not meet primary endpoint of OS60
Usually consists of high-dose topical steroids or nitrogen mustards; see paper for details.
===References===
# Kaye FJ, Bunn PA Jr, Steinberg SM, Stocker JL, Ihde DC, Fischmann AB, Glatstein EJ, Schechter GP, Phelps RM, Foss FM, Parlette HL, Anderson MJ, Sausville EA. A randomized trial comparing combination electron-beam radiation and chemotherapy with topical therapy in the initial treatment of mycosis fungoides. N Engl J Med. 1989 Dec 28;321(26):1784-90. link to original article EuroPMC
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=Relapsed or refractory=
==Alemtuzumab monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence	Efficacy
Lundin et al. 2003	Not reported 	Phase 2 	ORR: 55%
====Targeted therapy====
*Alemtuzumab (Campath) 3 mg IV once on day 1, then increased to 10 mg IV once as soon as infusion-related reactions tolerated, then increased to 30 mg IV once as soon as infusion-related reactions tolerated, then 30 mg IV 3 days per week
Up to 12-week course
===References===
# Lundin J, Hagberg H, Repp R, Cavallin-Ståhl E, Fredén S, Juliusson G, Rosenblad E, Tjønnfjord G, Wiklund T, Osterborg A. Phase 2 study of alemtuzumab (anti-CD52 monoclonal antibody) in patients with advanced mycosis fungoides/Sezary syndrome. Blood. 2003 Jun 1;101(11):4267-72. Epub 2003 Jan 23. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
==Belinostat monotherapy==
===Regimen===
Study 	Evidence	Efficacy
Foss et al. 2014 (PXD101-CLN-6)	Phase 2 	ORR: 14%
====Targeted therapy====
*Belinostat (Beleodaq) 1000 mg/m2 IV over 30 minutes once per day on days 1 to 5
21-day cycles
===References===
# PXD101-CLN-6: Foss F, Advani R, Duvic M, Hymes KB, Intragumtornchai T, Lekhakula A, Shpilberg O, Lerner A, Belt RJ, Jacobsen ED, Laurent G, Ben-Yehuda D, Beylot-Barry M, Hillen U, Knoblauch P, Bhat G, Chawla S, Allen LF, Pohlman B. A phase II trial of belinostat (PXD101) in patients with relapsed or refractory peripheral or cutaneous T-cell lymphoma. Br J Haematol. 2015 Mar;168(6):811-9. Epub 2014 Nov 17. link to original article dosing details in abstract have been reviewed by our editors EuroPMC NCT00274651
==Bendamustine monotherapy==
===Regimen===
Study 	Evidence	Efficacy
Demaj et al. 2013 (BENTLY)	Phase 2 	ORR: 50%
====Chemotherapy====
*Bendamustine 120 mg/m2 IV once per day on days 1 & 2
21-day cycle for 6 cycles
===References===
# BENTLY: Damaj G, Gressin R, Bouabdallah K, Cartron G, Choufi B, Gyan E, Banos A, Jaccard A, Park S, Tournilhac O, Schiano-de Collela JM, Voillat L, Joly B, Le Gouill S, Saad A, Cony-Makhoul P, Vilque JP, Sanhes L, Schmidt-Tanguy A, Bubenheim M, Houot R, Diouf M, Marolleau JP, Béné MC, Martin A, Lamy T. Results from a prospective, open-label, phase II trial of bendamustine in refractory or relapsed T-cell lymphomas: the BENTLY trial. J Clin Oncol. 2013 Jan 1;31(1):104-10. Epub 2012 Oct 29. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00959686
==Bexarotene monotherapy==
===Regimen variant #1, 48 weeks===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Prince et al. 2017 (ALCANZA)	2012-2015 	Phase 3 (C)	Brentuximab vedotin	Shorter PFS1Median PFS: 3.5 vs 16.7 mo(HR 3.70, 95% CI 2.33-5.88)
1Reported efficacy is based on the 2021 update.
Note: This dose is considered the target dose in ALCANZA.
====Targeted therapy====
*Bexarotene (Targretin) 300 mg/m2 PO once per day
48-week course
===Regimen variant #2, indefinite===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Duvic et al. 2001a	1996-1998 	Phase 2 (RT) 	 	ORR: 55%
Duvic et al. 2001b	1997-02 to 1998-11 	Phase 2/3 (E-RT-esc)	Bexarotene; 6.5 mg/m2/d	Higher ORR (primary endpoint)
Note: This dose is considered the optimal starting dose by Duvic et al. 2001a.
====Targeted therapy====
*Bexarotene (Targretin) 300 mg/m2 PO once per day
Continued indefinitely
===References===
# Duvic M, Hymes K, Heald P, Breneman D, Martin AG, Myskowski P, Crowley C, Yocum RC; Bexarotene Worldwide Study Group. Bexarotene is effective and safe for treatment of refractory advanced-stage cutaneous T-cell lymphoma: multinational phase II-III trial results. J Clin Oncol. 2001 May 1;19(9):2456-71. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# Duvic M, Martin AG, Kim Y, Olsen E, Wood GS, Crowley CA, Yocum RC; Worldwide Bexarotene Study Group. Phase 2 and 3 clinical trial of oral bexarotene (Targretin capsules) for the treatment of refractory or persistent early-stage cutaneous T-cell lymphoma. Arch Dermatol. 2001 May;137(5):581-93. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# ALCANZA: Prince HM, Kim YH, Horwitz SM, Dummer R, Scarisbrick J, Quaglino P, Zinzani PL, Wolter P, Sanches JA, Ortiz-Romero PL, Akilov OE, Geskin L, Trotman J, Taylor K, Dalle S, Weichenthal M, Walewski J, Fisher D, Dréno B, Stadler R, Feldman T, Kuzel TM, Wang Y, Palanca-Wessels MC, Zagadailov E, Trepicchio WL, Zhang W, Lin HM, Liu Y, Huebner D, Little M, Whittaker S, Duvic M; ALCANZA study group. Brentuximab vedotin or physician's choice in CD30-positive cutaneous T-cell lymphoma (ALCANZA): an international, open-label, randomised, phase 3, multicentre trial. Lancet. 2017 Aug 5;390(10094):555-566. Epub 2017 Jun 7. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01578499
##Update: Horwitz SM, Scarisbrick JJ, Dummer R, Whittaker S, Duvic M, Kim YH, Quaglino P, Zinzani PL, Bechter O, Eradat H, Pinter-Brown L, Akilov OE, Geskin L, Sanches JA, Ortiz-Romero PL, Weichenthal M, Fisher DC, Walewski J, Trotman J, Taylor K, Dalle S, Stadler R, Lisano J, Bunn V, Little M, Prince HM. Randomized phase 3 ALCANZA study of brentuximab vedotin vs physician's choice in cutaneous T-cell lymphoma: final data. Blood Adv. 2021 Dec 14;5(23):5098-5106. link to original article link to PMC article EuroPMC
==Bexarotene & Pralatrexate==
===Regimen===
Study 	Dates of enrollment	Evidence 	Efficacy
Duvic et al. 2017 (PDX-018)	2010-2015 	Phase 1/2	ORR: 60%
Note: This dose is the MTD. Note that the abstract contains a typo for bexarotene dosing; the authors have been contacted.
====Targeted therapy====
*Bexarotene (Targretin) 150 mg/m2 PO once per day on days 1 to 28
====Chemotherapy====
*Pralatrexate (Folotyn) 15 mg/m2 IV once per day on days 1, 8, 15
28-day cycles
===References===
# PDX-018: Duvic M, Kim YH, Zinzani PL, Horwitz SM. Results from a phase I/II open-label, dose-finding study of pralatrexate and oral bexarotene in patients with relapsed/refractory cutaneous T-cell lymphoma. Clin Cancer Res. 2017 Jul;23(14):3552-6. Epub 2017 Feb 6. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT01134341
==Brentuximab vedotin monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Kim et al. 2015 (SU-06212011-7946) 	Not reported 	Phase 2 	 	OGRR: 70% (90% CI, 53-83)
Duvic et al. 2015 (MDACC 2010-0914)	2011-2013 	Phase 2 	 	ORR: 73% (95% CI, 60-86)
Prince et al. 2017 (ALCANZA) 	2012-2015 	Phase 3 (E-RT-switch-ooc)	Investigator's choice of:1a. Bexarotene1b. Methotrexate	Longer PFS1 (secondary endpoint)Median PFS: 16.7 vs 3.5 mo(HR 0.27, 95% CI 0.17-0.43)Superior objective global response lasting at least 4 months (primary endpoint)
1Reported efficacy is based on the 2021 update.
====Antibody-drug conjugate therapy====
*Brentuximab vedotin (Adcetris) 1.8 mg/kg IV over 30 minutes once on day 1
21-day cycle for up to 16 cycles
===References===
# SU-06212011-7946: Kim YH, Tavallaee M, Sundram U, Salva KA, Wood GS, Li S, Rozati S, Nagpal S, Krathen M, Reddy S, Hoppe RT, Nguyen-Lin A, Weng WK, Armstrong R, Pulitzer M, Advani RH, Horwitz SM. Phase II investigator-initiated study of brentuximab vedotin in mycosis fungoides and Sézary syndrome with variable CD30 expression level: A multi-institution collaborative project. J Clin Oncol. 2015 Nov 10;33(32):3750-8. Epub 2015 Jul 20. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT01396070
# MDACC 2010-0914: Duvic M, Tetzlaff MT, Gangar P, Clos AL, Sui D, Talpur R. Results of a phase II trial of brentuximab vedotin for CD30+ cutaneous T-cell lymphoma and lymphomatoid papulosis. J Clin Oncol. 2015 Nov 10;33(32):3759-65. Epub 2015 Aug 10. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT01352520
# ALCANZA: Prince HM, Kim YH, Horwitz SM, Dummer R, Scarisbrick J, Quaglino P, Zinzani PL, Wolter P, Sanches JA, Ortiz-Romero PL, Akilov OE, Geskin L, Trotman J, Taylor K, Dalle S, Weichenthal M, Walewski J, Fisher D, Dréno B, Stadler R, Feldman T, Kuzel TM, Wang Y, Palanca-Wessels MC, Zagadailov E, Trepicchio WL, Zhang W, Lin HM, Liu Y, Huebner D, Little M, Whittaker S, Duvic M; ALCANZA study group. Brentuximab vedotin or physician's choice in CD30-positive cutaneous T-cell lymphoma (ALCANZA): an international, open-label, randomised, phase 3, multicentre trial. Lancet. 2017 Aug 5;390(10094):555-566. Epub 2017 Jun 7. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01578499
##Update: Horwitz SM, Scarisbrick JJ, Dummer R, Whittaker S, Duvic M, Kim YH, Quaglino P, Zinzani PL, Bechter O, Eradat H, Pinter-Brown L, Akilov OE, Geskin L, Sanches JA, Ortiz-Romero PL, Weichenthal M, Fisher DC, Walewski J, Trotman J, Taylor K, Dalle S, Stadler R, Lisano J, Bunn V, Little M, Prince HM. Randomized phase 3 ALCANZA study of brentuximab vedotin vs physician's choice in cutaneous T-cell lymphoma: final data. Blood Adv. 2021 Dec 14;5(23):5098-5106. link to original article link to PMC article EuroPMC
==Denileukin diftitox monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Olsen et al. 2001 (L4389-10) 	Not reported 	Phase 3 (E-RT-esc)	Denileukin diftitox; 9 mcg/kg 	Did not meet primary endpoint of ORR
Prince et al. 2010 (L4389-11)	Not reported 	Phase 3 (E-RT-esc)	1. Denileukin diftitox; 9 mcg/kg	Higher ORR (primary endpoint)
Prince et al. 2010 (L4389-11)	Not reported 	Phase 3 (E-RT-esc)	2. Placebo 	Longer PFS (secondary endpoint)
Note: Dose is that which was recommended in L4389-11 based on superior response. Up to 3 additional cycles allowed in L4389-10 for patients who had ongoing response.
====Targeted therapy====
*Denileukin diftitox (Ontak) 18 mcg/kg IV over 15 to 60 minutes once per day on days 1 to 5
====Supportive therapy====
*"Premedication with Acetaminophen (Tylenol) (650 mg in Olsen et al. 2001) and an antihistamine was required 30 to 60 minutes before each infusion" and could be used after infusions as needed.
*Olsen et al. 2001 used Promethazine (Phenergan) 25 mg or Prochlorperazine (Compazine) 10 mg (route/schedule not specified) as needed for nausea.
*Corticosteroid use was not allowed.
21-day cycles for up to 8 cycles (see note)
===References===
# L4389-10: Olsen E, Duvic M, Frankel A, Kim Y, Martin A, Vonderheid E, Jegasothy B, Wood G, Gordon M, Heald P, Oseroff A, Pinter-Brown L, Bowen G, Kuzel T, Fivenson D, Foss F, Glode M, Molina A, Knobler E, Stewart S, Cooper K, Stevens S, Craig F, Reuben J, Bacha P, Nichols J. Pivotal phase III trial of two dose levels of denileukin diftitox for the treatment of cutaneous T-cell lymphoma. J Clin Oncol. 2001 Jan 15;19(2):376-88. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# L4389-11: Prince HM, Duvic M, Martin A, Sterry W, Assaf C, Sun Y, Straus D, Acosta M, Negro-Vilar A. Phase III placebo-controlled trial of denileukin diftitox for patients with cutaneous T-cell lymphoma. J Clin Oncol. 2010 Apr 10;28(11):1870-7. Epub 2010 Mar 8. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00050999
# Meta-analysis: Duvic M, Geskin L, Prince HM. Duration of response in cutaneous T-cell lymphoma patients treated with denileukin diftitox: results from 3 phase III studies. Clin Lymphoma Myeloma Leuk. 2013 Aug;13(4):377-84. Epub 2013 Jun 14. link to original article EuroPMC
==Lenalidomide monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence	Efficacy
Querfeld et al. 2013 (NU 04H5)	2005-2010 	Phase 2 	ORR: 28%
Note: dose escalations only occurred if the prior dose was tolerated.
====Targeted therapy====
*Lenalidomide (Revlimid) as follows:
**Cycle 1: 10 mg PO once per day on days 1 to 21
**Cycle 2: 15 mg PO once per day on days 1 to 21
**Cycle 3: 20 mg PO once per day on days 1 to 21
**Cycles 4 to 26: 25 mg PO once per day on days 1 to 21
28-day cycle for up to 26 cycles (2 years)
===References===
# NU 04H5: Querfeld C, Rosen ST, Guitart J, Duvic M, Kim YH, Dusza SW, Kuzel TM. Results of an open-label multicenter phase II trial of lenalidomide monotherapy in refractory mycosis fungoides and Sezary syndrome. Blood. 2014 Feb 20;123(8):1159-66. Epub 2013 Dec 11. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00466921
==Methotrexate monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Prince et al. 2017 (ALCANZA)	2012-2015 	Phase 3 (C)	Brentuximab vedotin	Shorter PFS1Median PFS: 3.5 vs 16.7 mo(HR 3.70, 95% CI 2.33-5.88)
1Reported efficacy is based on the 2021 update.
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
====Chemotherapy====
*Methotrexate (MTX) 5 to 50 mg PO once on day 1
7-day cycle for 48 cycles
===References===
# Retrospective: Zackheim HS, Kashani-Sabet M, McMillan A. Low-dose methotrexate to treat mycosis fungoides: a retrospective study in 69 patients. J Am Acad Dermatol. 2003 Nov;49(5):873-8. link to original article EuroPMC
# ALCANZA: Prince HM, Kim YH, Horwitz SM, Dummer R, Scarisbrick J, Quaglino P, Zinzani PL, Wolter P, Sanches JA, Ortiz-Romero PL, Akilov OE, Geskin L, Trotman J, Taylor K, Dalle S, Weichenthal M, Walewski J, Fisher D, Dréno B, Stadler R, Feldman T, Kuzel TM, Wang Y, Palanca-Wessels MC, Zagadailov E, Trepicchio WL, Zhang W, Lin HM, Liu Y, Huebner D, Little M, Whittaker S, Duvic M; ALCANZA study group. Brentuximab vedotin or physician's choice in CD30-positive cutaneous T-cell lymphoma (ALCANZA): an international, open-label, randomised, phase 3, multicentre trial. Lancet. 2017 Aug 5;390(10094):555-566. Epub 2017 Jun 7. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01578499
##Update: Horwitz SM, Scarisbrick JJ, Dummer R, Whittaker S, Duvic M, Kim YH, Quaglino P, Zinzani PL, Bechter O, Eradat H, Pinter-Brown L, Akilov OE, Geskin L, Sanches JA, Ortiz-Romero PL, Weichenthal M, Fisher DC, Walewski J, Trotman J, Taylor K, Dalle S, Stadler R, Lisano J, Bunn V, Little M, Prince HM. Randomized phase 3 ALCANZA study of brentuximab vedotin vs physician's choice in cutaneous T-cell lymphoma: final data. Blood Adv. 2021 Dec 14;5(23):5098-5106. link to original article link to PMC article EuroPMC
==Mogamulizumab monotherapy==
===Regimen variant #1, 8-week course===
Study 	Dates of enrollment	Evidence
Ogura et al. 2014 (KW-0761-004)	Not reported 	Phase 2
====Targeted therapy====
*Mogamulizumab (Poteligeo) 1 mg/kg IV once on day 1
7-day cycle for 8 cycles
===Regimen variant #2, indefinite===
FDA-recommended dose
Study 	Dates of enrollment 	Evidence 	Comparator	Comparative Efficacy
Duvic et al. 2015 (KW-0761-001)	2009 to not reported	Phase 1/2 	 	
Kim et al. 2018 (MAVORIC) 	2012-2016 	Phase 3 (E-RT-switch-ooc)	Vorinostat	Longer PFS (primary endpoint)
Note: in KW-0761-001, a two-week "period of observation" was undertaken after cycle 1.
====Targeted therapy====
*Mogamulizumab (Poteligeo) as follows:
**Cycle 1: 1 mg/kg IV once per day on days 1, 8, 15, 22
**Cycle 2 onwards: 1 mg/kg IV once per day on days 1 & 15
28-day cycles
===References===
# KW-0761-004: Ogura M, Ishida T, Hatake K, Taniwaki M, Ando K, Tobinai K, Fujimoto K, Yamamoto K, Miyamoto T, Uike N, Tanimoto M, Tsukasaki K, Ishizawa K, Suzumiya J, Inagaki H, Tamura K, Akinaga S, Tomonaga M, Ueda R. Multicenter phase II study of mogamulizumab (KW-0761), a defucosylated anti-cc chemokine receptor 4 antibody, in patients with relapsed peripheral T-cell lymphoma and cutaneous T-cell lymphoma. J Clin Oncol. 2014 Apr 10;32(11):1157-63. Epub 2014 Mar 10. link to original article dosing details in abstract have been reviewed by our editors EuroPMC NCT01192984
# KW-0761-001: Duvic M, Pinter-Brown LC, Foss FM, Sokol L, Jorgensen JL, Challagundla P, Dwyer KM, Zhang X, Kurman MR, Ballerini R, Liu L, Kim YH. Phase 1/2 study of mogamulizumab, a defucosylated anti-CCR4 antibody, in previously treated patients with cutaneous T-cell lymphoma. Blood. 2015 Mar 19;125(12):1883-9. Epub 2015 Jan 20. link to original article dosing details in abstract have been reviewed by our editors link to PMC article EuroPMC NCT00888927
# MAVORIC: Kim YH, Bagot M, Pinter-Brown L, Rook AH, Porcu P, Horwitz SM, Whittaker S, Tokura Y, Vermeer M, Zinzani PL, Sokol L, Morris S, Kim EJ, Ortiz-Romero PL, Eradat H, Scarisbrick J, Tsianakas A, Elmets C, Dalle S, Fisher DC, Halwani A, Poligone B, Greer J, Fierro MT, Khot A, Moskowitz AJ, Musiek A, Shustov A, Pro B, Geskin LJ, Dwyer K, Moriya J, Leoni M, Humphrey JS, Hudgens S, Grebennik DO, Tobinai K, Duvic M; MAVORIC Investigators. Mogamulizumab versus vorinostat in previously treated cutaneous T-cell lymphoma (MAVORIC): an international, open-label, randomised, controlled phase 3 trial. Lancet Oncol. 2018 Sep;19(9):1192-1204. Epub 2018 Aug 9. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01728805
##HRQoL analysis: Ortiz Romero PL, Kim YH, Molloy K, Quaglino P, Scarisbrick J, Thornton S, Sandilands K, Dent JE, Nixon A, Williams A, Shinohara MM. Health-related quality of life in cutaneous T-cell lymphoma: A post hoc analysis of a phase 3 trial in mycosis fungoides and Sézary syndrome. J Eur Acad Dermatol Venereol. 2024 Sep 24. Epub ahead of print. link to original article EuroPMC
==Pralatrexate monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence	Efficacy
Horwitz et al. 2012	2007-08 to 2010-10 	Phase 2 	RR: 45%
Note: Dose is that identified as recommended based on de-escalation strategy.
====Chemotherapy====
*Pralatrexate (Folotyn) 15 mg/m2 IV push once per day on days 1, 8, 15
====Supportive therapy====
*Cyanocobalamin (Vitamin B12) 1 mg IM once every 8 to 10 weeks, within 10 weeks of treatment initiation
*Folic acid (Folate) 1 mg PO once per day, starting at least 10 days prior to treatment initiation
28-day cycles
===References===
# Horwitz SM, Kim YH, Foss F, Zain JM, Myskowski PL, Lechowicz MJ, Fisher DC, Shustov AR, Bartlett NL, Delioukina ML, Koutsoukos T, Saunders ME, O'Connor OA, Duvic M. Identification of an active, well-tolerated dose of pralatrexate in patients with relapsed or refractory cutaneous T-cell lymphoma. Blood. 2012 May 3;119(18):4115-22. Epub 2012 Mar 6. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Romidepsin monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Efficacy
Piekarz et al. 2009 (NIH 01-C-0049CTCL)	Not reported 	Phase 2 (RT)	ORR: 34% (95% CI, 23-46)
Whittaker et al. 2010 (GPI-04-0001) 	2005-2007 	Phase 2 (RT)	ORR: 34% (95% CI, 25-45)
====Targeted therapy====
*Romidepsin (Istodax) 14 mg/m2 IV over 4 hours once per day on days 1, 8, 15
28-day cycle for up to 6 cycles; optional extension of treatment for patients with SD or better
===References===
# NIH 01-C-0049CTCL: Piekarz RL, Frye R, Turner M, Wright JJ, Allen SL, Kirschbaum MH, Zain J, Prince HM, Leonard JP, Geskin LJ, Reeder C, Joske D, Figg WD, Gardner ER, Steinberg SM, Jaffe ES, Stetler-Stevenson M, Lade S, Fojo AT, Bates SE. Phase II multi-institutional trial of the histone deacetylase inhibitor romidepsin as monotherapy for patients with cutaneous T-cell lymphoma. J Clin Oncol. 2009 Nov 10;27(32):5410-7. Epub 2009 Oct 13. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT00007345
# GPI-04-0001: Whittaker SJ, Demierre MF, Kim EJ, Rook AH, Lerner A, Duvic M, Scarisbrick J, Reddy S, Robak T, Becker JC, Samtsov A, McCulloch W, Kim YH. Final results from a multicenter, international, pivotal study of romidepsin in refractory cutaneous T-cell lymphoma. J Clin Oncol. 2010 Oct 10;28(29):4485-91. Epub 2010 Aug 9. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00106431
==Vorinostat monotherapy==
===Regimen===
FDA-recommended dose
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Duvic et al. 2006 	Not reported 	Phase 2a (RT)	 	ORR: 24%
Olsen et al. 2007 (Merck 0683-001)	Not reported 	Phase 2b (RT)	 	ORR: 30%
Kim et al. 2018 (MAVORIC) 	2012-2016 	Phase 3 (C) 	Mogamulizumab	Shorter PFS
Note: Duvic et al. 2006 evaluated several different doses, but this is the one that "had the most favorable safety profile". To our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.
====Targeted therapy====
*Vorinostat (Zolinza) 400 mg PO once per day
28-day cycles
===References===
# Duvic M, Talpur R, Ni X, Zhang C, Hazarika P, Kelly C, Chiao JH, Reilly JF, Ricker JL, Richon VM, Frankel SR. Phase 2 trial of oral vorinostat (suberoylanilide hydroxamic acid, SAHA) for refractory cutaneous T-cell lymphoma (CTCL). Blood. 2007 Jan 1;109(1):31-9. Epub 2006 Sep 7. Erratum in: Blood. 2007 Jun 15;109(12):5086. link to original article link to PMC article dosing details in abstract have been reviewed by our editors EuroPMC
# Merck 0683-001: Olsen EA, Kim YH, Kuzel TM, Pacheco TR, Foss FM, Parker S, Frankel SR, Chen C, Ricker JL, Arduino JM, Duvic M. Phase IIb multicenter trial of vorinostat in patients with persistent, progressive, or treatment refractory cutaneous T-cell lymphoma. J Clin Oncol. 2007 Jul 20;25(21):3109-15. Epub 2007 Jun 18. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00091559
## Update: Duvic M, Olsen EA, Breneman D, Pacheco TR, Parker S, Vonderheid EC, Abuav R, Ricker JL, Rizvi S, Chen C, Boileau K, Gunchenko A, Sanz-Rodriguez C, Geskin LJ. Evaluation of the long-term tolerability and clinical benefit of vorinostat in patients with advanced cutaneous T-cell lymphoma. Clin Lymphoma Myeloma. 2009 Dec;9(6):412-6. link to original article EuroPMC
# MAVORIC: Kim YH, Bagot M, Pinter-Brown L, Rook AH, Porcu P, Horwitz SM, Whittaker S, Tokura Y, Vermeer M, Zinzani PL, Sokol L, Morris S, Kim EJ, Ortiz-Romero PL, Eradat H, Scarisbrick J, Tsianakas A, Elmets C, Dalle S, Fisher DC, Halwani A, Poligone B, Greer J, Fierro MT, Khot A, Moskowitz AJ, Musiek A, Shustov A, Pro B, Geskin LJ, Dwyer K, Moriya J, Leoni M, Humphrey JS, Hudgens S, Grebennik DO, Tobinai K, Duvic M; MAVORIC Investigators. Mogamulizumab versus vorinostat in previously treated cutaneous T-cell lymphoma (MAVORIC): an international, open-label, randomised, controlled phase 3 trial. Lancet Oncol. 2018 Sep;19(9):1192-1204. Epub 2018 Aug 9. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01728805
##HRQoL analysis: Ortiz Romero PL, Kim YH, Molloy K, Quaglino P, Scarisbrick J, Thornton S, Sandilands K, Dent JE, Nixon A, Williams A, Shinohara MM. Health-related quality of life in cutaneous T-cell lymphoma: A post hoc analysis of a phase 3 trial in mycosis fungoides and Sézary syndrome. J Eur Acad Dermatol Venereol. 2024 Sep 24. Epub ahead of print. link to original article EuroPMC
=Relapsed or refractory, subsequent lines of treatment=
==Denileukin diftitox monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Duvic et al. 2012 (L4389-14)	1995-09 to 2006-10 	Non-randomized
====Targeted therapy====
*Denileukin diftitox (Ontak) 18 mcg/kg IV once per day on days 1 to 5
21-day cycle for up to 8 cycles
===References===
# L4389-14: Duvic M, Martin AG, Olsen EA, Fivenson DP, Prince HM. Efficacy and safety of denileukin diftitox retreatment in patients with relapsed cutaneous T-cell lymphoma. Leuk Lymphoma. 2013 Mar;54(3):514-9. Epub 2012 Sep 3. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
=Consolidation, all lines of therapy=
==Busulfan & Fludarabine, then allo HSCT==
BuFlu: Busulfan & Fludarabine
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
de Masson et al. 2023 (CUTALLO)	2016-06-01 to 2022-03-03	Propensity score analysis (E-esc)	No transplant	Longer PFS (primary endpoint)Median PFS: 9 vs 3 mo(HR 0.38, 95% CI 0.21-0.69)
===References===
#CUTALLO: de Masson A, Beylot-Barry M, Ram-Wolff C, Mear JB, Dalle S, d'Incan M, Ingen-Housz-Oro S, Orvain C, Abraham J, Dereure O, Charbonnier A, Cornillon J, Longvert C, Barete S, Boulinguez S, Wierzbicka-Hainaut E, Aubin F, Rubio MT, Bernard M, Schmidt-Tanguy A, Houot R, Pham-Ledard A, Michonneau D, Brice P, Labussière-Wallet H, Bouaziz JD, Grange F, Moins-Teisserenc H, Jondeau K, Michel L, Mourah S, Battistella M, Daguindau E, Loschi M, Picard A, Franck N, Maillard N, Huynh A, Nguyen S, Marçais A, Chaby G, Ceballos P, Le Corre Y, Maury S, Bay JO, Adamski H, Bachy E, Forcade E, Socié G, Bagot M, Chevret S, Peffault de Latour R; CUTALLO Investigators; Groupe Français d'Etude des Lymphomes Cutanés; Société Française de Greffe de Moëlle et Thérapie Cellulaire. Allogeneic transplantation in advanced cutaneous T-cell lymphomas (CUTALLO): a propensity score matched controlled prospective study. Lancet. 2023 Jun 10;401(10392):1941-1950. Epub 2023 Apr 24. link to original article dosing details in supplement have been reviewed by our editors EuroPMC NCT02520908
==Busulfan, Fludarabine, Thiotepa, then allo HSCT==
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
de Masson et al. 2023 (CUTALLO)	2016-06-01 to 2022-03-03	Propensity score analysis (E-esc)	No transplant	Longer PFS (primary endpoint)Median PFS: 9 vs 3 mo(HR 0.38, 95% CI 0.21-0.69)
===References===
#CUTALLO: de Masson A, Beylot-Barry M, Ram-Wolff C, Mear JB, Dalle S, d'Incan M, Ingen-Housz-Oro S, Orvain C, Abraham J, Dereure O, Charbonnier A, Cornillon J, Longvert C, Barete S, Boulinguez S, Wierzbicka-Hainaut E, Aubin F, Rubio MT, Bernard M, Schmidt-Tanguy A, Houot R, Pham-Ledard A, Michonneau D, Brice P, Labussière-Wallet H, Bouaziz JD, Grange F, Moins-Teisserenc H, Jondeau K, Michel L, Mourah S, Battistella M, Daguindau E, Loschi M, Picard A, Franck N, Maillard N, Huynh A, Nguyen S, Marçais A, Chaby G, Ceballos P, Le Corre Y, Maury S, Bay JO, Adamski H, Bachy E, Forcade E, Socié G, Bagot M, Chevret S, Peffault de Latour R; CUTALLO Investigators; Groupe Français d'Etude des Lymphomes Cutanés; Société Française de Greffe de Moëlle et Thérapie Cellulaire. Allogeneic transplantation in advanced cutaneous T-cell lymphomas (CUTALLO): a propensity score matched controlled prospective study. Lancet. 2023 Jun 10;401(10392):1941-1950. Epub 2023 Apr 24. link to original article dosing details in supplement have been reviewed by our editors EuroPMC NCT02520908
==Fludarabine & Melphalan, then allo HSCT==
FluMel: Fludarabine & Melphalan
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
de Masson et al. 2023 (CUTALLO)	2016-06-01 to 2022-03-03	Propensity score analysis (E-esc)	No transplant	Longer PFS (primary endpoint)Median PFS: 9 vs 3 mo(HR 0.38, 95% CI 0.21-0.69)
===References===
#CUTALLO: de Masson A, Beylot-Barry M, Ram-Wolff C, Mear JB, Dalle S, d'Incan M, Ingen-Housz-Oro S, Orvain C, Abraham J, Dereure O, Charbonnier A, Cornillon J, Longvert C, Barete S, Boulinguez S, Wierzbicka-Hainaut E, Aubin F, Rubio MT, Bernard M, Schmidt-Tanguy A, Houot R, Pham-Ledard A, Michonneau D, Brice P, Labussière-Wallet H, Bouaziz JD, Grange F, Moins-Teisserenc H, Jondeau K, Michel L, Mourah S, Battistella M, Daguindau E, Loschi M, Picard A, Franck N, Maillard N, Huynh A, Nguyen S, Marçais A, Chaby G, Ceballos P, Le Corre Y, Maury S, Bay JO, Adamski H, Bachy E, Forcade E, Socié G, Bagot M, Chevret S, Peffault de Latour R; CUTALLO Investigators; Groupe Français d'Etude des Lymphomes Cutanés; Société Française de Greffe de Moëlle et Thérapie Cellulaire. Allogeneic transplantation in advanced cutaneous T-cell lymphomas (CUTALLO): a propensity score matched controlled prospective study. Lancet. 2023 Jun 10;401(10392):1941-1950. Epub 2023 Apr 24. link to original article dosing details in supplement have been reviewed by our editors EuroPMC NCT02520908
Category:Cutaneous T-cell lymphoma regimens
Category:Disease-specific pages
Category:Cutaneous lymphomas
Category:T-cell lymphomas