Cutaneous T-cell lymphoma

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Section editor
Bhagirathbhai Dholaria, MBBS
Vanderbilt University
Nashville, TN, USA
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Are you looking for a regimen but can't find it here? For placebo or observational studies in this condition, please visit this page. If you still can't find it, please let us know so we can add it!

  • We have moved How I Treat articles to a dedicated page.
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


NCCN


Upfront therapy

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

  1. 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 PubMed
  2. 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 PubMed 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

  1. 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 PubMed


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

  1. 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 PubMed


Belinostat monotherapy

Regimen

Study Evidence Efficacy
Foss et al. 2014 (PXD101-CLN-6) Phase 2 ORR: 14%

Targeted therapy

21-day cycles

References

  1. 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 PubMed NCT00274651


Bendamustine monotherapy

Regimen

Study Evidence Efficacy
Demaj et al. 2013 (BENTLY) Phase 2 ORR: 50%

Chemotherapy

21-day cycle for 6 cycles

References

  1. 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 PubMed 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 Inferior PFS1

1Reported efficacy is based on the 2021 update.
Note: This dose is considered the target dose in ALCANZA.

Targeted therapy

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 Superior ORR (primary endpoint)

Note: This dose is considered the optimal starting dose by Duvic et al. 2001a.

Targeted therapy

Continued indefinitely

References

  1. 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 PubMed
  2. 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 PubMed
  3. 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 PubMed NCT01578499
    1. 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 PubMed


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

Chemotherapy

28-day cycles

References

  1. 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 PubMed 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. Bexarotene
1b. Methotrexate 		Superior 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

21-day cycle for up to 16 cycles

References

  1. 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 PubMed NCT01396070
  2. 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 PubMed NCT01352520
  3. 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 PubMed NCT01578499
    1. 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 PubMed


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 Superior ORR (primary endpoint)
2. Placebo Superior 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

Supportive therapy

21-day cycles for up to 8 cycles (see note)

References

  1. 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 PubMed
  2. 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 PubMed NCT00050999
  3. 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 PubMed


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

  1. 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 PubMed NCT00466921


Methotrexate monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Prince et al. 2017 (ALCANZA) 2012-2015 Phase 3 (C) Brentuximab vedotin Inferior PFS1

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

7-day cycle for 48 cycles

References

  1. 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 PubMed
  2. 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 PubMed NCT01578499
    1. 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 PubMed


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

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 Superior 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

  1. 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 PubMed NCT01192984
  2. 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 PubMed NCT00888927
  3. 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 PubMed NCT01728805


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

Supportive therapy

28-day cycles

References

  1. 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 PubMed


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

28-day cycle for up to 6 cycles; optional extension of treatment for patients with SD or better

References

  1. 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 PubMed NCT00007345
  2. 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 PubMed 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 Inferior 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

28-day cycles

References

  1. 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 PubMed
  2. 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 PubMed NCT00091559
    1. 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 PubMed
  3. 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 PubMed NCT01728805


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

21-day cycle for up to 8 cycles

References

  1. 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 PubMed


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 Superior PFS (primary endpoint)
Median PFS: 9 vs 3 mo
(HR 0.38, 95% CI 0.21-0.69)

Chemotherapy

Immunotherapy

GVHD prophylaxis

  • Cyclosporine started on day -1, tapered on day +90 if no GVHD
  • Methotrexate (MTX) 15 mg/m2 IV once on day +1, then 10 mg/m2 IV once per day on days +3, +6, +11

One course

References

  1. 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 PubMed 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 Superior PFS (primary endpoint)
Median PFS: 9 vs 3 mo
(HR 0.38, 95% CI 0.21-0.69)

Note: this preparative regimen was intended for haploidentical HSCT.

Chemotherapy

Immunotherapy

GVHD prophylaxis

One course

References

  1. 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 PubMed 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 Superior PFS (primary endpoint)
Median PFS: 9 vs 3 mo
(HR 0.38, 95% CI 0.21-0.69)

Chemotherapy

Immunotherapy

GVHD prophylaxis

  • Cyclosporine started on day -1, tapered on day +90 if no GVHD
  • Methotrexate (MTX) 15 mg/m2 IV once on day +1, then 10 mg/m2 IV once per day on days +3, +6, +11

One course

References

  1. 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 PubMed NCT02520908


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