Peripheral T-cell lymphoma

Section editor
	Bhagirathbhai Dholaria, MBBS Vanderbilt University Nashville, TN, USA LinkedIn

30 regimens on this page 37 variants on this page

Are you looking for a regimen but can't find it here? It is possible that we've moved it to the historical regimens page. If you still can't find it, please let us know so we can add it!.
Note: some subtypes of PTCL have been moved to dedicated pages:

• Anaplastic large cell lymphoma
• Extranodal NK- and T-cell lymphoma, nasal type
• NK- and T-cell lymphoma

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

• 2015: d'Amore et al. Peripheral T-cell lymphomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed

• 2013: Dreyling et al. ESMO Consensus conferences: guidelines on malignant lymphoma. part 2: marginal zone lymphoma, mantle cell lymphoma, peripheral T-cell lymphoma. PubMed

NCCN

• NCCN does not currently have guidelines at this granular level; please see NCCN Guidelines - T-cell Lymphomas.

Untreated, randomized data

BV-CHP

BV-CHP: Brentuximab Vedotin, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Prednisone
A+CHP: Adcetris (Brentuximab vedotin), Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Prednisone

Regimen

FDA-recommended dose

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Horwitz et al. 2018 (ECHELON-2)	2013-2016	Phase 3 (E-RT-switch-ooc)	CHOP	Superior PFS (primary endpoint) Median PFS: 48.2 vs 20.8 mo (HR 0.71, 95% CI 0.54-0.93) Seems to have superior OS1 (secondary endpoint) OS60: 70.1% vs 61% (HR 0.72, 95% CI 0.53-0.99)

¹Reported efficacy is based on the 2021 update.

Antibody-drug conjugate therapy

• Brentuximab vedotin (Adcetris) 1.8 mg/kg IV once on day 1, given fourth

Chemotherapy

• Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
• Doxorubicin (Adriamycin) 50 mg/m² IV once on day 1

Glucocorticoid therapy

• Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5

21-day cycle for 6 to 8 cycles

References

1. ECHELON-2: Horwitz S, O'Connor OA, Pro B, Illidge T, Fanale M, Advani R, Bartlett NL, Christensen JH, Morschhauser F, Domingo-Domenech E, Rossi G, Kim WS, Feldman T, Lennard A, Belada D, Illés Á, Tobinai K, Tsukasaki K, Yeh SP, Shustov A, Hüttmann A, Savage KJ, Yuen S, Iyer S, Zinzani PL, Hua Z, Little M, Rao S, Woolery J, Manley T, Trümper L; ECHELON-2 Study Group. Brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma (ECHELON-2): a global, double-blind, randomised, phase 3 trial. Lancet. 2019 Jan 19;393(10168):229-240. Epub 2018 Dec 4. Erratum in: Lancet. 2019 Jan 19;393(10168):228. link to original article contains dosing details in abstract link to PMC article PubMed NCT01777152
   1. Update: Horwitz S, O'Connor OA, Pro B, Trümper L, Iyer S, Advani R, Bartlett NL, Christensen JH, Morschhauser F, Domingo-Domenech E, Rossi G, Kim WS, Feldman T, Menne T, Belada D, Illés Á, Tobinai K, Tsukasaki K, Yeh SP, Shustov A, Hüttmann A, Savage KJ, Yuen S, Zinzani PL, Miao H, Bunn V, Fenton K, Fanale M, Puhlmann M, Illidge T. The ECHELON-2 Trial: 5-year results of a randomized, phase III study of brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma. Ann Oncol. 2022 Mar;33(3):288-298. Epub 2021 Dec 16. link to original article PubMed

CHOP

CHOP: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone

Regimen variant #1, 6 cycles, 40 mg/m²

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Bachy et al. 2021 (LYSA Ro-CHOP)	2013-2017	Phase 3 (C)	Ro-CHOP	Might have inferior PFS1 (primary endpoint) Median PFS: 10.2 vs 12 mo (HR 1.27, 95% CI 0.995-1.61)

¹Reported efficacy is based on the 2024 update.

Chemotherapy

• Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
• Doxorubicin (Adriamycin) 50 mg/m² IV once on day 1
• Vincristine (Oncovin) by the following age-based criteria:
  • 70 years old or younger: 1.4 mg/m² (maximum dose of 2 mg) IV once on day 1
  • Older than 70 years old: 1.4 mg/m² (maximum dose of 1.5 mg) IV once on day 1

Glucocorticoid therapy

• Prednisone (Sterapred) 40 mg/m² PO once per day on days 1 to 5

21-day cycle for 6 cycles

Regimen variant #2, 6 cycles, prednisone 60 mg/m²

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Reimer et al. 2004	2000-2006	Non-randomized
Li et al. 2017 (hnslblzlzx2011-3)	2010-2016	Phase 3 (C)	GDPT	Inferior OS

Note: the abstract of Reimer et al. 2004 does not have dosing details.

Chemotherapy

• Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
• Doxorubicin (Adriamycin) 50 mg/m² IV once on day 1
• Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 1

Glucocorticoid therapy

• Prednisone (Sterapred) 60 mg/m² PO once per day on days 1 to 5

21-day cycle for 6 cycles

Regimen variant #2, 8 cycles

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Simon et al. 2010 (GOELAMS LTP95)	1996-2002	Phase 3 (C)	VIP-rABVD	Did not meet primary endpoint of EFS24

Chemotherapy

• Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
• Doxorubicin (Adriamycin) 50 mg/m² IV once on day 1
• Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 1

Glucocorticoid therapy

• Prednisone (Sterapred) 100 mg/m² PO once per day on days 1 to 5

21-day cycle for 8 cycles

Subsequent treatment

• GOELAMS LTP95, patients with initial bulky disease (diameter at least 5 cm): IFRT consolidation x 4000 cGy

References

1. Reimer P, Schertlin T, Rüdiger T, Geissinger E, Roth S, Kunzmann V, Weissinger F, Nerl C, Schmitz N, Müller-Hermelink HK, Wilhelm M. Myeloablative radiochemotherapy followed by autologous peripheral blood stem cell transplantation as first-line therapy in peripheral T-cell lymphomas: first results of a prospective multicenter study. Hematol J. 2004;5(4):304-11. link to original article does not contain dosing details PubMed
   1. Update: Reimer P, Rüdiger T, Geissinger E, Weissinger F, Nerl C, Schmitz N, Engert A, Einsele H, Müller-Hermelink HK, Wilhelm M. Autologous stem-cell transplantation as first-line therapy in peripheral T-cell lymphomas: results of a prospective multicenter study. J Clin Oncol. 2009 Jan 1;27(1):106-13. Epub 2008 Nov 24. link to original article PubMed
2. GOELAMS-LTP95: Simon A, Peoch M, Casassus P, Deconinck E, Colombat P, Desablens B, Tournilhac O, Eghbali H, Foussard C, Jaubert J, Vilque JP, Rossi JF, Lucas V, Delwail V, Thyss A, Maloisel F, Milpied N, le Gouill S, Lamy T, Gressin R. Upfront VIP-reinforced-ABVD (VIP-rABVD) is not superior to CHOP/21 in newly diagnosed peripheral T cell lymphoma: results of the randomized phase III trial GOELAMS-LTP95. Br J Haematol. 2010 Oct;151(2):159-66. Epub 2010 Aug 25. link to original article contains dosing details in manuscript PubMed
3. Meta-analysis: Abouyabis AN, Shenoy PJ, Sinha R, Flowers CR, Lechowicz MJ. A systematic review and meta-analysis of front-line anthracycline-based chemotherapy regimens for peripheral T-cell lymphoma. ISRN Hematol. 2011;2011:623924. Epub 2011 Jun 16. link to original article link to PMC article PubMed
4. hnslblzlzx2011-3: Li L, Duan W, Zhang L, Li X, Fu X, Wang X, Wu J, Sun Z, Zhang X, Chang Y, Nan F, Yan J, Li Z, Young KH, Zhang M. The efficacy and safety of gemcitabine, cisplatin, prednisone, thalidomide versus CHOP in patients with newly diagnosed peripheral T-cell lymphoma with analysis of biomarkers. Br J Haematol. 2017 Sep;178(5):772-780. Epub 2017 Jun 9. link to original article contains dosing details in manuscript PubMed NCT01664975
5. ECHELON-2: Horwitz S, O'Connor OA, Pro B, Illidge T, Fanale M, Advani R, Bartlett NL, Christensen JH, Morschhauser F, Domingo-Domenech E, Rossi G, Kim WS, Feldman T, Lennard A, Belada D, Illés Á, Tobinai K, Tsukasaki K, Yeh SP, Shustov A, Hüttmann A, Savage KJ, Yuen S, Iyer S, Zinzani PL, Hua Z, Little M, Rao S, Woolery J, Manley T, Trümper L; ECHELON-2 Study Group. Brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma (ECHELON-2): a global, double-blind, randomised, phase 3 trial. Lancet. 2019 Jan 19;393(10168):229-240. Epub 2018 Dec 4. Erratum in: Lancet. 2019 Jan 19;393(10168):228. link to original article contains dosing details in abstract link to PMC article PubMed NCT01777152
   1. Update: Horwitz S, O'Connor OA, Pro B, Trümper L, Iyer S, Advani R, Bartlett NL, Christensen JH, Morschhauser F, Domingo-Domenech E, Rossi G, Kim WS, Feldman T, Menne T, Belada D, Illés Á, Tobinai K, Tsukasaki K, Yeh SP, Shustov A, Hüttmann A, Savage KJ, Yuen S, Zinzani PL, Miao H, Bunn V, Fenton K, Fanale M, Puhlmann M, Illidge T. The ECHELON-2 Trial: 5-year results of a randomized, phase III study of brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma. Ann Oncol. 2022 Mar;33(3):288-298. Epub 2021 Dec 16. link to original article PubMed
6. LYSA Ro-CHOP: Bachy E, Camus V, Thieblemont C, Sibon D, Casasnovas RO, Ysebaert L, Damaj G, Guidez S, Pica GM, Kim WS, Lim ST, André M, García-Sancho AM, Penarrubia MJ, Staber PB, Trotman J, Hüttmann A, Stefoni V, Re A, Gaulard P, Delfau-Larue MH, de Leval L, Meignan M, Li J, Morschhauser F, Delarue R. Romidepsin Plus CHOP Versus CHOP in Patients With Previously Untreated Peripheral T-Cell Lymphoma: Results of the Ro-CHOP Phase III Study (Conducted by LYSA). J Clin Oncol. 2022 Jan 20;40(3):242-251. Epub 2021 Nov 29. link to original article contains dosing details in manuscript PubMed NCT01796002
   1. Update: Camus V, Thieblemont C, Gaulard P, Cheminant M, Casasnovas RO, Ysebaert L, Damaj GL, Guidez S, Pica GM, Kim WS, Lim ST, Andre M, Gutiérrez N, Penarrubia MJ, Staber PB, Trotman J, Hüttmann A, Stefoni V, Tucci A, Fogarty P, Farhat H, Abraham J, Abarah W, Belmecheri F, Ribrag V, Delfau-Larue MH, Cottereau AS, Itti E, Li J, Delarue R, de Leval L, Morschhauser F, Bachy E. Romidepsin Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone Versus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Patients With Previously Untreated Peripheral T-Cell Lymphoma: Final Analysis of the Ro-CHOP Trial. J Clin Oncol. 2024 May 10;42(14):1612-1618. Epub 2024 Feb 16. link to original article PubMed

CHOP-14 (Prednisolone)

CHOP-14: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisolone every 14 days

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Wulf et al. 2020 (ACT-2)	2007-2013	Phase 3 (C)	A-CHOP-14	Did not meet primary endpoint of EFS

Preceding treatment

• ACT-2: Vincristine & Prednisolone pre-phase

Chemotherapy

• Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
• Doxorubicin (Adriamycin) 50 mg/m² IV once on day 1
• Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 1

Glucocorticoid therapy

• Prednisolone (Millipred) 100 mg PO once per day on days 1 to 5

Supportive therapy

• G-CSF support

14-day cycle for 6 cycles

References

1. ACT-2: Wulf GG, Altmann B, Ziepert M, D'Amore F, Held G, Greil R, Tournilhac O, Relander T, Viardot A, Wilhelm M, Wilhelm C, Pezzutto A, Zijlstra JM, van den Neste E, Lugtenburg PJ, Doorduijn JK, Gelder MV, van Imhoff GW, Zettl F, Braulke F, Nickelsen M, Glass B, Rosenwald A, Gaulard P, Loeffler M, Pfreundschuh M, Schmitz N, Trümper L; DSHNHL. Alemtuzumab plus CHOP versus CHOP in elderly patients with peripheral T-cell lymphoma: the DSHNHL2006-1B/ACT-2 trial. Leukemia. 2021 Jan;35(1):143-155. Epub 2020 May 7. link to original article contains dosing details in manuscript PubMed

CMED

CMED: Cyclophosphamide, Methotrexate, Etoposide, Dexamethasone

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Avilés et al. 2008	1994-2001	Phase 3 (E-switch-ic)	CHOP	Superior OS (co-primary endpoint)

Chemotherapy

• Cyclophosphamide (Cytoxan) 2000 mg/m² IV once on day 1
• Methotrexate (MTX) 300 mg/m² IV once on day 1
• Etoposide (Vepesid) 400 mg/m² IV once per day on days 1 & 2

Glucocorticoid therapy

• Dexamethasone (Decadron) 20 mg/m² PO once per day on days 1 to 5

Supportive therapy

• Leucovorin (Folinic acid) 15 mg IV every 6 hours for 12 doses, started 24 hours after MTX

14-day cycle for 6 cycles

References

1. Avilés A, Castañeda C, Neri N, Cleto S, Talavera A, González M, Huerta-Guzmán J, Nambo MJ. Results of a phase III clinical trial: CHOP versus CMED in peripheral T-cell lymphoma unspecified. Med Oncol. 2008;25(3):360-4. Epub 2008 Feb 5. link to original article contains dosing details in manuscript PubMed

GDPT

GDPT: Gemcitabine, DDP (Cisplatin), Prednisone, Thalidomide

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Li et al. 2017 (hnslblzlzx2011-3)	2010-2016	Phase 3 (E-switch-ooc)	CHOP	Superior OS24 (secondary endpoint) OS24: 71% vs 50%

Chemotherapy

• Gemcitabine (Gemzar) 800 mg/m² IV over 30 minutes once per day on days 1 & 8
• Cisplatin (Platinol) 25 mg/m² IV once per day on days 1 to 3

Glucocorticoid therapy

• Prednisone (Sterapred) 60 mg/m² PO once per day on days 1 to 5

Targeted therapy

• Thalidomide (Thalomid) 50 mg PO once per day, increased by 50 mg per day until target dose of 200 mg PO once per day

Supportive therapy

• Aspirin 100 mg PO once per day

21-day cycle for 6 cycles

References

1. hnslblzlzx2011-3: Li L, Duan W, Zhang L, Li X, Fu X, Wang X, Wu J, Sun Z, Zhang X, Chang Y, Nan F, Yan J, Li Z, Young KH, Zhang M. The efficacy and safety of gemcitabine, cisplatin, prednisone, thalidomide versus CHOP in patients with newly diagnosed peripheral T-cell lymphoma with analysis of biomarkers. Br J Haematol. 2017 Sep;178(5):772-780. Epub 2017 Jun 9. link to original article contains dosing details in manuscript PubMed NCT01664975

Untreated, non-randomized or retrospective data

A-CHOP

A-CHOP: Alemtuzumab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Predniso(lo)ne
CHOP-AL: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Predniso(lo)ne, ALemtuzumab
CHOP-C: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Predniso(lo)ne, Campath (Alemtuzumab)

Regimen variant #1, 2 cycles

Study	Dates of enrollment	Evidence
Corradini et al. 2014 (PTCL-06)	2006-2010	Phase 2

Note: These are the details for "Clin A" which was the regimen used for patients younger than 60. Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.

Chemotherapy

• Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
• Doxorubicin (Adriamycin) 50 mg/m² IV once on day 1
• Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 1

Glucocorticoid therapy

• Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5

Targeted therapy

• Alemtuzumab (Campath) as follows:
  • Cycle 1: 3 mg IV once on day -2, then 10 mg IV once on day -1, then 20 mg IV once on day 0
  • Cycle 2: 30 mg IV once on day 0 (= day 21 of cycle 1)

21-day cycle for 2 cycles

Subsequent treatment

• HyperCHidam consolidation x 2

Regimen variant #2, 8 cycles

Study	Dates of enrollment	Evidence
Gallamini et al. 2007	2003-01 to 2005-12	Phase 2

Note: the paper reports using the CHOP dosing as specified by Fisher et al. 1993; however, note that the cycle length here is 28 days.

Chemotherapy

• Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
• Doxorubicin (Adriamycin) 50 mg/m² IV once on day 1
• Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 1

Glucocorticoid therapy

• Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5

Targeted therapy

• Alemtuzumab (Campath) as follows:
  • Cycle 1: 3 mg IV once on day -2, then 10 mg IV once on day -1, then 20 mg IV once on day 0, then 30 mg IV once on day 1
  • Cycles 2 to 8: 30 mg IV once on day 1

Supportive therapy

• Chlorpheniramine (Chlor-Trimeton) 10 mg IV once per infusion; 60 minutes prior to alemtuzumab
• Acetaminophen (Tylenol) 500 mg PO once per infusion; 30 minutes prior to alemtuzumab
• Alizapride (Litican) 100 mg IV once per infusion; 30 minutes prior to alemtuzumab

28-day cycle for 8 cycles

References

1. Gallamini A, Zaja F, Patti C, Billio A, Specchia MR, Tucci A, Levis A, Manna A, Secondo V, Rigacci L, Pinto A, Iannitto E, Zoli V, Torchio P, Pileri S, Tarella C. Alemtuzumab (Campath-1H) and CHOP chemotherapy as first-line treatment of peripheral T-cell lymphoma: results of a GITIL (Gruppo Italiano Terapie Innovative nei Linfomi) prospective multicenter trial. Blood. 2007 Oct 1;110(7):2316-23. Epub 2007 Jun 20. link to original article contains partial protocol PubMed
2. PTCL-06: Corradini P, Vitolo U, Rambaldi A, Miceli R, Patriarca F, Gallamini A, Olivieri A, Benedetti F, Todeschini G, Rossi G, Salvi F, Bruno B, Baldini L, Ferreri A, Patti C, Tarella C, Pileri S, Dodero A. Intensified chemo-immunotherapy with or without stem cell transplantation in newly diagnosed patients with peripheral T-cell lymphoma. Leukemia. 2014 Sep;28(9):1885-91. Epub 2014 Feb 20. link to original article contains dosing details in manuscript PubMed EudraCT 2006-004234-33

CHOEP-14

CHOEP-14: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Etoposide, Prednisone every 14 days

Regimen

Study	Dates of enrollment	Evidence
d'Amore et al. 2012 (NLG-T-01)	2001-10 to 2007-10	Phase 2

Chemotherapy

• Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
• Doxorubicin (Adriamycin) 50 mg/m² IV once on day 1
• Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 1
• Etoposide (Vepesid) by the following age-based criteria:
  • 60 years old or younger: 100 mg/m² IV once per day on days 1 to 3

Glucocorticoid therapy

• Prednisone (Sterapred) 50 mg PO twice per day on days 1 to 5

14-day cycle for 6 cycles

Subsequent treatment

• If patients in PR or CR after three cycles, stem cells are mobilized off of cycles 5 and 6, followed by BEAC or BEAM auto HSCT consolidation

References

1. NLG-T-01: d'Amore F, Relander T, Lauritzsen GF, Jantunen E, Hagberg H, Anderson H, Holte H, Österborg A, Merup M, Brown P, Kuittinen O, Erlanson M, Østenstad B, Fagerli UM, Gadeberg OV, Sundström C, Delabie J, Ralfkiaer E, Vornanen M, Toldbod HE. Up-front autologous stem-cell transplantation in peripheral T-cell lymphoma: NLG-T-01. J Clin Oncol. 2012 Sep 1;30(25):3093-9. Epub 2012 Jul 30. link to original article contains dosing details in manuscript PubMed NCT00791947

CHOP & Everolimus

CHOP & Everolimus: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Predniso(lo)ne, Everolimus

Regimen

Study	Dates of enrollment	Evidence	Efficacy
Kim et al. 2016 (RADCHOP)	2011-03 to 2013-06	Phase 2	ORR: 90%

Chemotherapy

• Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
• Doxorubicin (Adriamycin) 50 mg/m² IV once on day 1
• Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 1

Glucocorticoid therapy

• Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5

Targeted therapy

• Everolimus (Afinitor) 5 mg PO once per day on days 1 to 14

21-day cycle for up to 6 cycles

References

1. RADCHOP: Kim SJ, Shin DY, Kim JS, Yoon DH, Lee WS, Lee H, Do YR, Kang HJ, Eom HS, Ko YH, Lee SH, Yoo HY, Hong M, Suh C, Kim WS. A phase II study of everolimus (RAD001), an mTOR inhibitor plus CHOP for newly diagnosed peripheral T-cell lymphomas. Ann Oncol. 2016 Apr;27(4):712-8. Epub 2016 Feb 8. link to original article contains dosing details in manuscript PubMed NCT01198665

DA-EPOCH

DA-EPOCH: Dose Adjusted Etoposide, Prednisone, Oncovin (Vincristine), Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin)

Regimen

Study	Dates of enrollment	Evidence	Efficacy
Maeda et al. 2017 (West-JHOG PTCL0707)	2007-09 to 2011-10	Phase 2	ORR: 78% (95% CI 62-89)

Note: the authors state that they followed the Wilson et al. 2002 protocol, but there are some differences, in particular 1) it isn't clear whether prednisone is given once or twice per day; and 2) dose adjustments below level 1 are different based on age.

Chemotherapy

• Etoposide (Vepesid) 50 mg/m²/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 200 mg/m²)
• Vincristine (Oncovin) 0.4 mg/m²/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 1.6 mg/m²)
• Cyclophosphamide (Cytoxan) 750 mg/m² IV over 2 hours once on day 5
• Doxorubicin (Adriamycin) 10 mg/m²/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 40 mg/m²)

Glucocorticoid therapy

• Prednisone (Sterapred) 60 mg/m²/day PO on days 1 to 5

Supportive therapy

• G-CSF starting on day 6 and continuing until ANC greater than 5000/μL past nadir
• Trimethoprim-Sulfamethoxazole (Bactrim DS) (dose not specified)
• Fluconazole (Diflucan) (dose not specified)

21-day cycle for 6 to 8 cycles

Dose and schedule modifications

• Start cycle 1 as described above.
• Obtain CBCs twice per week for nadir measurements.
• If nadir ANC greater than 500/μL, increase etoposide, doxorubicin, and cyclophosphamide by 20% compared to previous cycle.
• If nadir ANC less than 500/μL on 1 or 2 measurements, use same doses as last cycle.
• If nadir ANC less than 500/μL on at least 3 measurements, decrease etoposide, doxorubicin, and cyclophosphamide by 20% compared to previous cycle.
• And/or if nadir platelet count less than 25 x 10⁹/L on at least 1 measurement, decrease etoposide, doxorubicin, and cyclophosphamide by 20% compared to previous cycle.
• Younger than 70 years old: Dose adjustments below the cycle 1 starting dose only apply to cyclophosphamide. That is, the lowest etoposide and doxorubicin would be dosed is at the original cycle 1 dose.
• Patients 70 and older: Dose adjustments below the cycle 1 starting dose apply to all drugs
• (Presumed, based on Wilson et al. 2002): Can start new cycle every 21 days if ANC greater than 1000/μL and platelets greater than 100 x 10⁹/L. If counts are below those levels, check daily CBC and continue growth factor support until counts are adequate and next cycle can start.

References

1. Maeda Y, Nishimori H, Yoshida I, Hiramatsu Y, Uno M, Masaki Y, Sunami K, Masunari T, Nawa Y, Yamane H, Gomyo H, Takahashi T, Yano T, Matsuo K, Ohshima K, Nakamura S, Yoshino T, Tanimoto M. Dose-adjusted EPOCH chemotherapy for untreated peripheral T-cell lymphomas: a multicenter phase II trial of West-JHOG PTCL0707. Haematologica. 2017 Dec;102(12):2097-2103. Epub 2017 Sep 29. link to original article contains dosing details in manuscript link to PMC article PubMed UMIN000000829

DD-CHOP

DD-CHOP: Denileukin, Diftitox, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Predniso(lo)ne

Regimen

Study	Evidence	Efficacy
Foss et al. 2013 (CONCEPT)	Phase 2	ORR: 65%

Targeted therapy

• Denileukin diftitox (Ontak) 18 mcg/kg IV over 60 minutes once per day on days 1 & 2

Chemotherapy

• Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 3
• Doxorubicin (Adriamycin) 50 mg/m² IV once on day 3
• Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 3

Glucocorticoid therapy

• Prednisone (Sterapred) 100 mg PO once per day on days 3 to 7

Supportive therapy

• Dexamethasone (Decadron) 4 to 8 mg IV or PO once per day on days 1 & 2, prior to denileukin diftitox
• Acetaminophen (Tylenol) 650 mg PO once per day on days 1 & 2, prior to denileukin diftitox
• Diphenhydramine (Benadryl) 25 mg IV once per day on days 1 & 2, prior to denileukin diftitox
• Normal saline 250 to 500 cc IV, given before and after each denileukin diftitox infusion
• Antiemetics "per institutional standard"
• G-CSF support beginning on day 4

21-day cycle for 6 to 8 cycles

References

1. CONCEPT: Foss FM, Sjak-Shie N, Goy A, Jacobsen E, Advani R, Smith MR, Komrokji R, Pendergrass K, Bolejack V. A multicenter phase II trial to determine the safety and efficacy of combination therapy with denileukin diftitox and cyclophosphamide, doxorubicin, vincristine and prednisone in untreated peripheral T-cell lymphoma: the CONCEPT study. Leuk Lymphoma. 2013 Jul;54(7):1373-9. Epub 2013 Jan 29. link to original article contains dosing details in manuscript PubMed NCT00211185

HyperCHidam

HyperCHidam: Hyperfractionated Cyclophosphamide, Hiigh-dose ara-c (Cytarabine) & methotrexate

Regimen

Study	Dates of enrollment	Evidence
Corradini et al. 2014 (PTCL-06)	2006-2010	Phase 2

Note: These are the details for "Clin A" which was the regimen used for patients younger than 60. Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.

Preceding treatment

• PTCL-06: CHOP-AL induction x 2

Chemotherapy

• Methotrexate (MTX) 1600 mg/m² IV continuous infusion (duration not specified), started on day 1
• Cyclophosphamide (Cytoxan) 300 mg/m² IV every 12 hours for 3 days (start day not specified)
• Cytarabine (Ara-C) 2000 mg/m² IV every 12 hours for 3 days (start day not specified)

Supportive therapy

• Granulocyte-colony stimulating factor (type not specified) 5 mcg/kg once per day was given from day +5 (stop date not specified)

2 cycles (duration not specified)

Subsequent treatment

• PTCL-06, responders (PR/CR): allogeneic HSCT consolidation

References

1. PTCL-06: Corradini P, Vitolo U, Rambaldi A, Miceli R, Patriarca F, Gallamini A, Olivieri A, Benedetti F, Todeschini G, Rossi G, Salvi F, Bruno B, Baldini L, Ferreri A, Patti C, Tarella C, Pileri S, Dodero A. Intensified chemo-immunotherapy with or without stem cell transplantation in newly diagnosed patients with peripheral T-cell lymphoma. Leukemia. 2014 Sep;28(9):1885-91. Epub 2014 Feb 20. link to original article contains dosing details in manuscript PubMed EudraCT 2006-004234-33

Consolidation after upfront therapy

BEAM, then auto HSCT

BEAM: BiCNU (Carmustine), Etoposide, Ara-C (Cytarabine), Melphalan

Regimen variant #1

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Schmitz et al. 2021 (MYS-07-HMO-CTIL)	2011-2014	Phase 3 (C)	Fludarabine, Busulfan, Cyclophosphamide, then allo HSCT	Did not meet primary endpoint of EFS36

Preceding treatment

• MYS-07-HMO-CTIL: CHOEP-14 induction x 4, then DHAP consolidation x 1

Chemotherapy

• Carmustine (BCNU) 300 mg/m² IV once on day -7
• Etoposide (Vepesid) 200 mg/m² IV once per day on days -6 to -3
• Cytarabine (Ara-C) 200 mg/m² IV every 12 hours on days -6 to -3 (total dose: 1600 mg/m²)
• Melphalan (Alkeran) 140 mg/m² IV once on day -2

Supportive therapy

• Autologous stem cells re-infused on day 0

One course

Regimen variant #2

Study	Dates of enrollment	Evidence
d'Amore et al. 2012 (NLG-T-01)	2001-10 to 2007-10	Phase 2

Chemotherapy

• Carmustine (BCNU) 300 mg/m² IV once on day -6
• Etoposide (Vepesid) 100 mg/m² IV every 12 hours on days -5 to -2 (total dose: 800 mg/m²)
• Cytarabine (Ara-C) 200 mg/m² IV every 12 hours on days -5 to -2 (total dose: 1600 mg/m²)
• Melphalan (Alkeran) 140 mg/m² IV once on day -1

Supportive therapy

• Autologous stem cells re-infused on day 0
• (described in some publications)
• Filgrastim (Neupogen) by the following weight-based criteria:
  • Less than 70 kg: 300 mcg SC once per day, starting on day +7 after stem cell transplant
  • More than 70 kg (reference did not clarify which dosage to use for patients who are exactly 70 kg): 480 mcg SC once per day, starting on day +7 after stem cell transplant
• Trimethoprim-Sulfamethoxazole (Bactrim DS) 160/800 mg PO twice per day on Monday and Thursdays, until 6 months after BEAM
• Ciprofloxacin (Cipro) 500 mg PO twice per day while ANC less than 500/μL
• Antifungal prophylaxis with one of the following:
  • Fluconazole (Diflucan) 100 mg PO once per day while ANC less than 500/μL
  • Nystatin (Mycostatin) 500,000 units swish & swallow four times per day while ANC less than 500/μL
• Acyclovir (Zovirax) 400 mg PO three times per day while ANC less than 500/μL

One course

References

1. NLG-T-01: d'Amore F, Relander T, Lauritzsen GF, Jantunen E, Hagberg H, Anderson H, Holte H, Österborg A, Merup M, Brown P, Kuittinen O, Erlanson M, Østenstad B, Fagerli UM, Gadeberg OV, Sundström C, Delabie J, Ralfkiaer E, Vornanen M, Toldbod HE. Up-front autologous stem-cell transplantation in peripheral T-cell lymphoma: NLG-T-01. J Clin Oncol. 2012 Sep 1;30(25):3093-9. Epub 2012 Jul 30. link to original article contains dosing details in manuscript PubMed NCT00791947
2. MYS-07-HMO-CTIL: Schmitz N, Truemper L, Bouabdallah K, Ziepert M, Leclerc M, Cartron G, Jaccard A, Reimer P, Wagner E, Wilhelm M, Sanhes L, Lamy T, de Leval L, Rosenwald A, Roussel M, Kroschinsky F, Lindemann W, Dreger P, Viardot A, Milpied N, Gisselbrecht C, Wulf G, Gyan E, Gaulard P, Bay JO, Glass B, Poeschel V, Damaj G, Sibon D, Delmer A, Bilger K, Banos A, Haenel M, Dreyling M, Metzner B, Keller U, Braulke F, Friedrichs B, Nickelsen M, Altmann B, Tournilhac O. A randomized phase 3 trial of autologous vs allogeneic transplantation as part of first-line therapy in poor-risk peripheral T-NHL. Blood. 2021 May 13;137(19):2646-2656. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00984412

Cyclophosphamide & TBI, then auto HSCT

Cy/TBI: Cyclophosphamide & Total Body Irradiation

Regimen

Study	Dates of enrollment	Evidence
Reimer et al. 2004	2000-2006	Non-randomized

Chemotherapy

• Cyclophosphamide (Cytoxan) 60 mg/kg IV once per day on days -3 & -2

Radiotherapy

• Total body irradiation (TBI) 1200 cGy in fractions on days –6 to –4 (pulmonary dosage was limited to 800 cGy)

Supportive therapy

• Autologous stem cells re-infused on day 0

One course

References

1. Reimer P, Schertlin T, Rüdiger T, Geissinger E, Roth S, Kunzmann V, Weissinger F, Nerl C, Schmitz N, Müller-Hermelink HK, Wilhelm M. Myeloablative radiochemotherapy followed by autologous peripheral blood stem cell transplantation as first-line therapy in peripheral T-cell lymphomas: first results of a prospective multicenter study. Hematol J. 2004;5(4):304-11. link to original article PubMed
   1. Update: Reimer P, Rüdiger T, Geissinger E, Weissinger F, Nerl C, Schmitz N, Engert A, Einsele H, Müller-Hermelink HK, Wilhelm M. Autologous stem-cell transplantation as first-line therapy in peripheral T-cell lymphomas: results of a prospective multicenter study. J Clin Oncol. 2009 Jan 1;27(1):106-13. Epub 2008 Nov 24. link to original article contains dosing details in manuscript PubMed

Radiation therapy

Regimen

Study	Dates of enrollment	Evidence
Simon et al. 2010 (GOELAMS LTP95)	1996-2002	Non-randomized part of phase 3 RCT

Preceding treatment

• GOELAMS LTP95: CHOP x 8 versus vVIP-rABVD induction

Radiotherapy

• External beam radiotherapy 4000 cGy at 180 cGy/day to the involved field

4.5-week course

References

1. GOELAMS-LTP95: Simon A, Peoch M, Casassus P, Deconinck E, Colombat P, Desablens B, Tournilhac O, Eghbali H, Foussard C, Jaubert J, Vilque JP, Rossi JF, Lucas V, Delwail V, Thyss A, Maloisel F, Milpied N, le Gouill S, Lamy T, Gressin R. Upfront VIP-reinforced-ABVD (VIP-rABVD) is not superior to CHOP/21 in newly diagnosed peripheral T cell lymphoma: results of the randomized phase III trial GOELAMS-LTP95. Br J Haematol. 2010 Oct;151(2):159-66. Epub 2010 Aug 25. link to original article contains dosing details in manuscript PubMed

TFC, then allo HSCT

TFC: Thiotepa, Fludarabine, Cyclophosphamide

Regimen

Study	Dates of enrollment	Evidence
Corradini et al. 2002	1998-09 to 2001-01	Non-randomized
Corradini et al. 2014 (PTCL-06)	2006-11 to 2010-11	Phase 2

Details to be completed.

Preceding treatment

• PTCL-06: CHOP-AL induction x 2, then HyperCHidam consolidation x 2

Chemotherapy

• Thiotepa (Thioplex)
• Fludarabine (Fludara)
• Cyclophosphamide (Cytoxan)

Immunotherapy

• Allogeneic stem cells

Stem cells transfused on day 0

References

1. Corradini P, Tarella C, Olivieri A, Gianni AM, Voena C, Zallio F, Ladetto M, Falda M, Lucesole M, Dodero A, Ciceri F, Benedetti F, Rambaldi A, Sajeva MR, Tresoldi M, Pileri A, Bordignon C, Bregni M. Reduced-intensity conditioning followed by allografting of hematopoietic cells can produce clinical and molecular remissions in patients with poor-risk hematologic malignancies. Blood. 2002 Jan 1;99(1):75-82. link to original article PubMed
2. PTCL-06: Corradini P, Vitolo U, Rambaldi A, Miceli R, Patriarca F, Gallamini A, Olivieri A, Benedetti F, Todeschini G, Rossi G, Salvi F, Bruno B, Baldini L, Ferreri A, Patti C, Tarella C, Pileri S, Dodero A. Intensified chemo-immunotherapy with or without stem cell transplantation in newly diagnosed patients with peripheral T-cell lymphoma. Leukemia. 2014 Sep;28(9):1885-91. Epub 2014 Feb 20. link to original article contains dosing details in manuscript PubMed EudraCT 2006-004234-33

Relapsed or refractory, randomized data

Bendamustine monotherapy

Regimen variant #1, 90 mg/m²

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Dupuis et al. 2024 (ORACLE)	2018-11-09 to 2021-02-22	Phase 3 (C)	Oral azacitidine	Did not meet primary endpoint of PFS

Note: The majority of patients in ORACLE had angioimmunoblastic T-cell lymphoma (AITL). This was the lower bound of dosing in ORACLE.

Chemotherapy

• Bendamustine 90 mg/m² IV once per day on days 1 & 2

21-day cycle for 6 cycles

Regimen variant #2, 120 mg/m²

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Demaj et al. 2013 (BENTLY)	2009-2011	Phase 2		ORR: 50%
Dupuis et al. 2024 (ORACLE)	2018-11-09 to 2021-02-22	Phase 3 (C)	Oral azacitidine	Did not meet primary endpoint of PFS

Note: The majority of patients in ORACLE had angioimmunoblastic T-cell lymphoma (AITL). This was the upper bound of dosing in ORACLE.

Chemotherapy

• Bendamustine 120 mg/m² IV once per day on days 1 & 2

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 contains dosing details in manuscript PubMed NCT00959686
2. ORACLE: Dupuis J, Bachy E, Morschhauser F, Cartron G, Fukuhara N, Daguindau N, Casasnovas RO, Snauwaert S, Gressin R, Fox CP, d'Amore FA, Staber PB, Tournilhac O, Bouabdallah K, Thieblemont C, André M, Rai S, Ennishi D, Gkasiamis A, Nishio M, Fornecker LM, Delfau-Larue MH, Sako N, Mule S, de Leval L, Gaulard P, Tsukasaki K, Lemonnier F. Oral azacitidine compared with standard therapy in patients with relapsed or refractory follicular helper T-cell lymphoma (ORACLE): an open-label randomised, phase 3 study. Lancet Haematol. 2024 Jun;11(6):e406-e414. link to original article contains dosing details in manuscript PubMed NCT03593018

DHAP

DHAP: Dexamethasone, High-dose Ara-C (Cytarabine), Platinol (Cisplatin)

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Crump et al. 2014 (NCIC-CTG LY.12)	2003-2011	Phase 3 (C)	GDP	Inconclusive whether non-inferior ORR1

¹Reported efficacy is based on the 2017 subgroup analysis.

Chemotherapy

• Cytarabine (Ara-C) 2000 mg/m² IV over 3 hours every 12 hours on day 2 (total dose per cycle: 4000 mg/m²)
• Cisplatin (Platinol) 100 mg/m² IV continuous infusion over 24 hours, started on day 1

Glucocorticoid therapy

• Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4

21-day cycle for up to 3 cycles

References

1. NCIC-CTG LY.12: Crump M, Kuruvilla J, Couban S, MacDonald DA, Kukreti V, Kouroukis CT, Rubinger M, Buckstein R, Imrie KR, Federico M, Di Renzo N, Howson-Jan K, Baetz T, Kaizer L, Voralia M, Olney HJ, Turner AR, Sussman J, Hay AE, Djurfeldt MS, Meyer RM, Chen BE, Shepherd LE. Randomized comparison of gemcitabine, dexamethasone, and cisplatin versus dexamethasone, cytarabine, and cisplatin chemotherapy before autologous stem-cell transplantation for relapsed and refractory aggressive lymphomas: NCIC-CTG LY.12. J Clin Oncol. 2014 Nov 1;32(31):3490-6. Epub 2014 Sep 29. link to original article contains dosing details in manuscript PubMed NCT00078949
   1. Subgroup analysis: Skamene T, Crump M, Savage KJ, Reiman T, Kuruvilla J, Good D, LeBrun D, Meyer RM, Sehn LH, Soulières D, Stakiw J, Laferriere N, Luminari S, Shepherd LE, Djurfeldt M, Zhu L, Chen BE, Hay AE. Salvage chemotherapy and autologous stem cell transplantation for peripheral T-cell lymphoma: a subset analysis of the Canadian Cancer Trials Group LY.12 randomized phase 3 study(). Leuk Lymphoma. 2017 Oct;58(10):2319-2327. Epub 2017 May 15. link to original article PubMed

GDP

GDP: Gemcitabine, Dexamethasone, Platinol (Cisplatin)

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Crump et al. 2014 (NCIC-CTG LY.12)	2003-2011	Phase 3 (E-switch-ic)	DHAP	Inconclusive whether non-inferior ORR1 (co-primary endpoint)

¹Reported efficacy is based on the 2017 subgroup analysis.

Chemotherapy

• Gemcitabine (Gemzar) 1000 mg/m² IV once per day on days 1 & 8
• Cisplatin (Platinol) 75 mg/m² IV once on day 1

Glucocorticoid therapy

• Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4

21-day cycle for up to 3 cycles

References

1. NCIC-CTG LY.12: Crump M, Kuruvilla J, Couban S, MacDonald DA, Kukreti V, Kouroukis CT, Rubinger M, Buckstein R, Imrie KR, Federico M, Di Renzo N, Howson-Jan K, Baetz T, Kaizer L, Voralia M, Olney HJ, Turner AR, Sussman J, Hay AE, Djurfeldt MS, Meyer RM, Chen BE, Shepherd LE. Randomized comparison of gemcitabine, dexamethasone, and cisplatin versus dexamethasone, cytarabine, and cisplatin chemotherapy before autologous stem-cell transplantation for relapsed and refractory aggressive lymphomas: NCIC-CTG LY.12. J Clin Oncol. 2014 Nov 1;32(31):3490-6. Epub 2014 Sep 29. link to original article contains dosing details in manuscript PubMed NCT00078949
   1. Subgroup analysis: Skamene T, Crump M, Savage KJ, Reiman T, Kuruvilla J, Good D, LeBrun D, Meyer RM, Sehn LH, Soulières D, Stakiw J, Laferriere N, Luminari S, Shepherd LE, Djurfeldt M, Zhu L, Chen BE, Hay AE. Salvage chemotherapy and autologous stem cell transplantation for peripheral T-cell lymphoma: a subset analysis of the Canadian Cancer Trials Group LY.12 randomized phase 3 study(). Leuk Lymphoma. 2017 Oct;58(10):2319-2327. Epub 2017 May 15. link to original article PubMed

Gemcitabine monotherapy

Regimen variant #1, 1000 mg/m²; 3 weeks out of 4

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
O'Connor et al. 2019 (LUMIERE)	2012-2014	Phase 3 (C)	Alisertib	Did not meet co-primary endpoints of ORR/PFS

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

• Gemcitabine (Gemzar) 1000 mg/m² IV over 30 minutes once per day on days 1, 8, 15

28-day cycles

Regimen variant #2, 1200 mg/m²; 3 weeks out of 4

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Dupuis et al. 2024 (ORACLE)	2018-11-09 to 2021-02-22	Phase 3 (C)	Oral azacitidine	Did not meet primary endpoint of PFS

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. The majority of patients in this study had angioimmunoblastic T-cell lymphoma (AITL).

Chemotherapy

• Gemcitabine (Gemzar) 1200 mg/m² IV over 30 minutes once per day on days 1, 8, 15

28-day cycle for 6 cycles

References

1. LUMIERE: O'Connor OA, Özcan M, Jacobsen ED, Roncero JM, Trotman J, Demeter J, Masszi T, Pereira J, Ramchandren R, Beaven A, Caballero D, Horwitz SM, Lennard A, Turgut M, Hamerschlak N, d'Amore FA, Foss F, Kim WS, Leonard JP, Zinzani PL, Chiattone CS, Hsi ED, Trümper L, Liu H, Sheldon-Waniga E, Ullmann CD, Venkatakrishnan K, Leonard EJ, Shustov AR; Lumiere Study Investigators. Randomized phase III study of alisertib or investigator's choice (selected single agent) in patients with relapsed or refractory peripheral T-cell lymphoma. J Clin Oncol. 2019 Mar 10;37(8):613-623. Epub 2019 Feb 1. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01482962
2. ORACLE: Dupuis J, Bachy E, Morschhauser F, Cartron G, Fukuhara N, Daguindau N, Casasnovas RO, Snauwaert S, Gressin R, Fox CP, d'Amore FA, Staber PB, Tournilhac O, Bouabdallah K, Thieblemont C, André M, Rai S, Ennishi D, Gkasiamis A, Nishio M, Fornecker LM, Delfau-Larue MH, Sako N, Mule S, de Leval L, Gaulard P, Tsukasaki K, Lemonnier F. Oral azacitidine compared with standard therapy in patients with relapsed or refractory follicular helper T-cell lymphoma (ORACLE): an open-label randomised, phase 3 study. Lancet Haematol. 2024 Jun;11(6):e406-e414. link to original article contains dosing details in manuscript PubMed NCT03593018

Pralatrexate monotherapy

Example orders

• Example orders for Pralatrexate (Folotyn) in peripheral T-cell lymphoma

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
O'Connor et al. 2011 (PROPEL)	2006-2008	Phase 2 (RT)		ORR: 29%
O'Connor et al. 2019 (LUMIERE)	2012-2014	Phase 3 (C)	Alisertib	Did not meet co-primary endpoints of ORR/PFS

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

• Pralatrexate (Folotyn) 30 mg/m² IV over 3 to 5 minutes once per day on days 1, 8, 15, 22, 29, 36

Supportive therapy

• Cyanocobalamin (Vitamin B12) 1 mg IM once every 8 to 10 weeks
• Folic acid (Folate) 1 to 1.25 mg PO once per day
  • "Elevated methylmalonic acid (greater than 200 nmol/L) and/or homocysteine (greater than 10 µmol/L) at screening required initiation of Folic acid (Folate) and Cyanocobalamin (Vitamin B12) at least 10 days before the first dose of pralatrexate."

7-week cycles

References

1. PROPEL: O'Connor OA, Pro B, Pinter-Brown L, Bartlett N, Popplewell L, Coiffier B, Lechowicz MJ, Savage KJ, Shustov AR, Gisselbrecht C, Jacobsen E, Zinzani PL, Furman R, Goy A, Haioun C, Crump M, Zain JM, Hsi E, Boyd A, Horwitz S. Pralatrexate in patients with relapsed or refractory peripheral T-cell lymphoma: results from the pivotal PROPEL study. J Clin Oncol. 2011 Mar 20;29(9):1182-9. Epub 2011 Jan 18. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00364923
2. LUMIERE: Connor OA, Özcan M, Jacobsen ED, Roncero JM, Trotman J, Demeter J, Masszi T, Pereira J, Ramchandren R, Beaven A, Caballero D, Horwitz SM, Lennard A, Turgut M, Hamerschlak N, d'Amore FA, Foss F, Kim WS, Leonard JP, Zinzani PL, Chiattone CS, Hsi ED, Trümper L, Liu H, Sheldon-Waniga E, Ullmann CD, Venkatakrishnan K, Leonard EJ, Shustov AR; Lumiere Study Investigators. Randomized phase III study of alisertib or investigator's choice (selected single agent) in patients with relapsed or refractory peripheral T-cell lymphoma. J Clin Oncol. 2019 Mar 10;37(8):613-623. Epub 2019 Feb 1. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01482962

Romidepsin monotherapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Dupuis et al. 2024 (ORACLE)	2018-11-09 to 2021-02-22	Phase 3 (C)	Oral azacitidine	Did not meet primary endpoint of PFS

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. The majority of patients in this study had angioimmunoblastic T-cell lymphoma (AITL).

Targeted therapy

• Romidepsin (Istodax) 14 mg/m² IV once per day on days 1, 8, 15

28-day cycles

References

1. ORACLE: Dupuis J, Bachy E, Morschhauser F, Cartron G, Fukuhara N, Daguindau N, Casasnovas RO, Snauwaert S, Gressin R, Fox CP, d'Amore FA, Staber PB, Tournilhac O, Bouabdallah K, Thieblemont C, André M, Rai S, Ennishi D, Gkasiamis A, Nishio M, Fornecker LM, Delfau-Larue MH, Sako N, Mule S, de Leval L, Gaulard P, Tsukasaki K, Lemonnier F. Oral azacitidine compared with standard therapy in patients with relapsed or refractory follicular helper T-cell lymphoma (ORACLE): an open-label randomised, phase 3 study. Lancet Haematol. 2024 Jun;11(6):e406-e414. link to original article contains dosing details in manuscript PubMed NCT03593018

Relapsed or refractory, non-randomized or retrospective data

Belinostat monotherapy

Regimen

Study	Dates of enrollment	Evidence	Efficacy
Foss et al. 2014 (PXD101-CLN-6)	2006-2009	Phase 2	ORR: 25%
O'Connor et al. 2015 (BELIEF)	2009-2011	Phase 2 (RT)	ORR: 26%

Targeted therapy

• Belinostat (Beleodaq) 1000 mg/m² IV over 30 minutes once per day on days 1 to 5

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 contains dosing details in abstract PubMed NCT00274651
2. BELIEF: O'Connor OA, Horwitz S, Masszi T, Van Hoof A, Brown P, Doorduijn J, Hess G, Jurczak W, Knoblauch P, Chawla S, Bhat G, Choi MR, Walewski J, Savage K, Foss F, Allen LF, Shustov A. Belinostat in patients with relapsed or refractory peripheral T-cell lymphoma: results of the pivotal phase II BELIEF (CLN-19) study. J Clin Oncol. 2015 Aug 10;33(23):2492-9. Epub 2015 Jun 22. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00865969

Brentuximab vedotin monotherapy

Regimen

Study	Dates of enrollment	Evidence	Efficacy
Horwitz et al. 2014 (SGN35-012CD30+T-NHL)	2011-09 to 2012-11	Phase 2	ORR: 41%

Antibody-drug conjugate therapy

• Brentuximab vedotin (Adcetris) 1.8 mg/kg IV over 30 minutes once on day 1

21-day cycles

References

1. SGN35-012_CD30+T-NHL: Horwitz SM, Advani RH, Bartlett NL, Jacobsen ED, Sharman JP, O'Connor OA, Siddiqi T, Kennedy DA, Oki Y. Objective responses in relapsed T-cell lymphomas with single-agent brentuximab vedotin. Blood. 2014 May 15;123(20):3095-100. Epub 2014 Mar 20. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01421667

Chidamide monotherapy

Regimen

Study	Dates of enrollment	Evidence	Efficacy
Shi et al. 2015	2010-04 to 2012-05	Phase 2	ORR: 28%

Targeted therapy

• Chidamide (Epidaza) 30 mg PO twice per week

Continued indefinitely

References

1. Shi Y, Dong M, Hong X, Zhang W, Feng J, Zhu J, Yu L, Ke X, Huang H, Shen Z, Fan Y, Li W, Zhao X, Qi J, Huang H, Zhou D, Ning Z, Lu X. Results from a multicenter, open-label, pivotal phase II study of chidamide in relapsed or refractory peripheral T-cell lymphoma. Ann Oncol. 2015 Aug;26(8):1766-71. Epub 2015 Jun 23. link to original article contains dosing details in abstract PubMed ChiCTR-TNC-10000811

Darinaparsin monotherapy

Regimen

Study	Dates of enrollment	Evidence
Kim et al. 2023 (SP-02)	NR	Phase 2

Antineoplastic therapy

• Darinaparsin (Darvias) 300 mg/m² IV over 60 minutes once per day on days 1 to 5

21-day cycles

References

1. SP-02: Kim WS, Fukuhara N, Yoon DH, Yamamoto K, Uchida T, Negoro E, Izutsu K, Terui Y, Nakajima H, Ando K, Suehiro Y, Kang HJ, Ko PS, Nagahama F, Sonehara Y, Nagai H, Tien HF, Kwong YL, Tobinai K. Darinaparsin in patients with relapsed or refractory peripheral T-cell lymphoma: results of an Asian phase 2 study. Blood Adv. 2023 Sep 12;7(17):4903-4912. link to original article link to PMC article contains dosing details in abstract PubMed NCT02653976

Duvelisib monotherapy

Regimen

Study	Dates of enrollment	Evidence
Awaiting publication (PRIMO)	2018-ongoing	Phase 2

Note: This is the dose used in the expansion phase; this trial remains unpublished.

Targeted therapy

• Duvelisib (Copiktra) as follows:
  • Cycles 1 & 2: 75 mg PO twice per day on days 1 to 28
  • Cycle 3 onwards: 25 mg PO twice per day on days 1 to 28

28-day cycles

References

1. PRIMO: NCT03372057

Forodesine monotherapy

Regimen

Study	Dates of enrollment	Evidence	Efficacy
Maruyama et al. 2018 (FDS-J02)	2013-01 to 2017-02	Phase 1/2	ORR: 22%

Chemotherapy

• Forodesine (Fodosine) 300 mg PO twice per day

Continued indefinitely

References

1. FDS-J02: Maruyama D, Tsukasaki K, Uchida T, Maeda Y, Shibayama H, Nagai H, Kurosawa M, Suehiro Y, Hatake K, Ando K, Yoshida I, Hidaka M, Murayama T, Okitsu Y, Tsukamoto N, Taniwaki M, Suzumiya J, Tamura K, Yamauchi T, Ueda R, Tobinai K. Multicenter phase 1/2 study of forodesine in patients with relapsed peripheral T cell lymphoma. Ann Hematol. 2019 Jan;98(1):131-142. Epub 2018 Jul 5. Erratum in: Ann Hematol. 2018 Jul 27. link to original article contains dosing details in abstract link to PMC article PubMed NCT01776411

Lenalidomide monotherapy

Regimen variant #1, limited duration

Study	Evidence	Efficacy
Morschhauser et al. 2013 (EXPECT)	Phase 2	ORR: 41%

Targeted therapy

• Lenalidomide (Revlimid) 25 mg PO once per day on days 1 to 21

28-day cycle for up to 26 cycles (2 years)

Regimen variant #2, indefinite

Study	Dates of enrollment	Evidence	Efficacy
Dueck et al. 2010	2006-09 to 2008-11	Phase 2	ORR: 30%

Targeted therapy

• Lenalidomide (Revlimid) 25 mg PO once per day on days 1 to 21

28-day cycles

References

1. Dueck G, Chua N, Prasad A, Finch D, Stewart D, White D, van der Jagt R, Johnston J, Belch A, Reiman T. Interim report of a phase 2 clinical trial of lenalidomide for T-cell non-Hodgkin lymphoma. Cancer. 2010 Oct 1;116(19):4541-8. link to original article contains dosing details in manuscript PubMed NCT00322985
   1. Update: Toumishey E, Prasad A, Dueck G, Chua N, Finch D, Johnston J, van der Jagt R, Stewart D, White D, Belch A, Reiman T. Final report of a phase 2 clinical trial of lenalidomide monotherapy for patients with T-cell lymphoma. Cancer. 2015 Mar 1;121(5):716-23. Epub 2014 Oct 29. link to original article PubMed
2. EXPECT: Morschhauser F, Fitoussi O, Haioun C, Thieblemont C, Quach H, Delarue R, Glaisner S, Gabarre J, Bosly A, Lister J, Li J, Coiffier B. A phase 2, multicentre, single-arm, open-label study to evaluate the safety and efficacy of single-agent lenalidomide (Revlimid®) in subjects with relapsed or refractory peripheral T-cell non-Hodgkin lymphoma: The EXPECT trial. Eur J Cancer. 2013 Sep;49(13):2869-76. Epub 2013 May 31. link to original article contains dosing details in abstract PubMed NCT00655668

Mogamulizumab monotherapy

Regimen

Study	Dates of enrollment	Evidence
Ogura et al. 2014 (KW-0761-004)	NR	Phase 2

Targeted therapy

• Mogamulizumab (Poteligeo) 1 mg/kg IV once per day on days 1, 8, 15, 22

28-day cycle for 2 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 contains dosing details in abstract PubMed NCT01192984

Consolidation after salvage therapy

Fludarabine, Busulfan, Cyclophosphamide, then allo HSCT

FluBuCy: Fludarabine, Busulfan, Cyclophosphamide

Regimen variant #1, oral

Study	Dates of enrollment	Evidence
Glass et al. 2014 (DSHNHL R3)	2004-06-16 to 2009-03-24	Phase 2

Chemotherapy

• Fludarabine (Fludara) 25 mg/m²/day IV on days -8 to -4
• Busulfan (Myleran) 4 mg/kg/day PO on days -6 to -4
• Cyclophosphamide (Cytoxan) 60 mg/kg/day IV on days -3 and -2

Immunotherapy

• Allogeneic stem cells transfused on day 0

GVHD prophylaxis

• Antithymocyte globulin, rabbit ATG (Thymoglobulin) 2 mg/kg IV from day -3 to -1 (unclear if this is a total dose or a daily dose)
  • Option also to use ATG-Fresenius S at a higher dose of 10 mg/kg
• Tacrolimus (Prograf) 8 to 12 mcg/L (route/frequency not specified) starting on day -1, tapered from day +100 in absence of GVHD
• Mycophenolate mofetil (CellCept) 1000 mg (route not specified) twice per day from day +1 to +28

One course

Regimen variant #2, intravenous

Study	Dates of enrollment	Evidence
Glass et al. 2014 (DSHNHL R3)	2004-06-16 to 2009-03-24	Phase 2

Chemotherapy

• Fludarabine (Fludara) 25 mg/m²/day IV on days -8 to -4
• Busulfan (Myleran) 3.2 mg/kg/day IV on days -6 to -4
• Cyclophosphamide (Cytoxan) 60 mg/kg/day IV on days -3 and -2

Immunotherapy

• Allogeneic stem cells transfused on day 0

GVHD prophylaxis

• Antithymocyte globulin, rabbit ATG (Thymoglobulin) 2 mg/kg IV from day -3 to -1 (unclear if this is a total dose or a daily dose)
  • Option also to use ATG-Fresenius S at a higher dose of 10 mg/kg
• Tacrolimus (Prograf) 8 to 12 mcg/L (route/frequency not specified) starting on day -1, tapered from day +100 in absence of GVHD
• Mycophenolate mofetil (CellCept) 1000 mg (route not specified) twice per day from day +1 to +28

One course

References

1. DSHNHL R3: Glass B, Hasenkamp J, Wulf G, Dreger P, Pfreundschuh M, Gramatzki M, Silling G, Wilhelm C, Zeis M, Görlitz A, Pfeiffer S, Hilgers R, Truemper L, Schmitz N; German High-Grade Lymphoma Study Group. Rituximab after lymphoma-directed conditioning and allogeneic stem-cell transplantation for relapsed and refractory aggressive non-Hodgkin lymphoma (DSHNHL R3): an open-label, randomised, phase 2 trial. Lancet Oncol. 2014 Jun;15(7):757-66. Epub 2014 May 11. link to original article link to original protocol (in German) contains dosing details in manuscript PubMed NCT00785330