Adult T-cell leukemia-lymphoma

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

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.

5 regimens on this page 5 variants on this page

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

NCCN

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

Untreated

CHOP-14

CHOP-14: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Predniso(lo)ne every 14 days
CHOP-DI: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Predniso(lo)ne, Dose-Intense
I-CHOP: Intensive Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Predniso(lo)ne

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy	Comparative Toxicity
Itoh et al. 2002 (JCOG 9505)	1995-1998	Randomized Phase 2 (E-de-esc)	dose-escalated CHOP	Did not meet primary endpoint of CR rate	Less toxic
Tsukasaki et al. 2007 (JCOG 9801)	1998-2003	Phase 3 (C)	mLSG15	Did not meet primary endpoint of OS	Less toxic

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

Supportive therapy

• Filgrastim (Neupogen) given once ANC decreased to less than 1000/μL and continued once per day until count increased to greater than 5000/μL

14-day cycle for 8 cycles

CNS therapy

Intrathecal triple-therapy was given during recovery phase of cycles 1, 3, and 5 after platelet count was greater than 70 x 10⁹/L.

• Cytarabine (Ara-C) 40 mg IT
• Methotrexate (MTX) 15 mg IT
• Prednisone (Sterapred) 10 mg IT

3 doses, total

References

1. JCOG 9505: Itoh K, Ohtsu T, Fukuda H, Sasaki Y, Ogura M, Morishima Y, Chou T, Aikawa K, Uike N, Mizorogi F, Ohno T, Ikeda S, Sai T, Taniwaki M, Kawano F, Niimi M, Hotta T, Shimoyama M, Tobinai K; JCOG. Randomized phase II study of biweekly CHOP and dose-escalated CHOP with prophylactic use of lenograstim (glycosylated G-CSF) in aggressive non-Hodgkin's lymphoma: Japan Clinical Oncology Group Study 9505. Ann Oncol. 2002 Sep;13(9):1347-55. link to original article PubMed
2. JCOG 9801: Tsukasaki K, Utsunomiya A, Fukuda H, Shibata T, Fukushima T, Takatsuka Y, Ikeda S, Masuda M, Nagoshi H, Ueda R, Tamura K, Sano M, Momita S, Yamaguchi K, Kawano F, Hanada S, Tobinai K, Shimoyama M, Hotta T, Tomonaga M; JCOG. VCAP-AMP-VECP compared with biweekly CHOP for adult T-cell leukemia-lymphoma: Japan Clinical Oncology Group Study JCOG9801. J Clin Oncol. 2007 Dec 1;25(34):5458-64. Epub 2007 Oct 29. link to original article contains dosing details in manuscript PubMed NCT00145002

mLSG15

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Tsukasaki et al. 2007 (JCOG 9801)	1998-2003	Phase 3 (E-esc)	CHOP-14	Did not meet primary endpoint of OS
Ishida et al. 2015 (Kyowa 0761-003)	2010-2011	Randomized Phase 2 (C)	mLSG15 & Mogamulizumab	Did not meet primary endpoint of CR rate

Note: Ranimustine is not available in the United States and is approved only in Japan.

Chemotherapy

• Vincristine (Oncovin) 1 mg/m² (maximum dose of 2 mg) IV once on day 1
• Cyclophosphamide (Cytoxan) 350 mg/m² IV once on day 1
• Doxorubicin (Adriamycin) 40 mg/m² IV once on day 1, then 30 mg/m² IV once on day 8
• Ranimustine (Cymerin) 60 mg/m² IV once on day 8
• Vindesine (Eldisine) 2.4 mg/m² IV once on day 15
• Etoposide (Vepesid) 100 mg/m² IV once per day on days 15 to 17
• Carboplatin (Paraplatin) 250 mg/m² IV once on day 15

Glucocorticoid therapy

• Prednisone (Sterapred) 40 mg/m² PO once per day on days 1, 8, 15 to 17

28-day cycle for 6 cycles

CNS therapy, prophylaxis

• Cytarabine (Ara-C) 40 mg IT, admixed with MTX & prednisone
• Methotrexate (MTX) 15 mg IT, admixed with Ara-C & prednisone
• Prednisone (Sterapred) 10 mg IT, admixed with Ara-C & MTX

Given after cycles 1, 3, and 5 after platelets greater than 70 x 10⁹/L and within 2 days before the next cycle

References

1. JCOG 9801: Tsukasaki K, Utsunomiya A, Fukuda H, Shibata T, Fukushima T, Takatsuka Y, Ikeda S, Masuda M, Nagoshi H, Ueda R, Tamura K, Sano M, Momita S, Yamaguchi K, Kawano F, Hanada S, Tobinai K, Shimoyama M, Hotta T, Tomonaga M; JCOG. VCAP-AMP-VECP compared with biweekly CHOP for adult T-cell leukemia-lymphoma: Japan Clinical Oncology Group Study JCOG9801. J Clin Oncol. 2007 Dec 1;25(34):5458-64. Epub 2007 Oct 29. link to original article contains dosing details in manuscript PubMed NCT00145002
2. Kyowa 0761-003: Ishida T, Jo T, Takemoto S, Suzushima H, Uozumi K, Yamamoto K, Uike N, Saburi Y, Nosaka K, Utsunomiya A, Tobinai K, Fujiwara H, Ishitsuka K, Yoshida S, Taira N, Moriuchi Y, Imada K, Miyamoto T, Akinaga S, Tomonaga M, Ueda R. Dose-intensified chemotherapy alone or in combination with mogamulizumab in newly diagnosed aggressive adult T-cell leukaemia-lymphoma: a randomized phase II study. Br J Haematol. 2015 Jun;169(5):672-82. Epub 2015 Mar 2. link to original article link to PMC article PubMed NCT01173887

Relapsed or refractory

Alemtuzumab monotherapy

Regimen

Study	Dates of enrollment	Evidence
Sharma et al. 2016	2004-2009	Phase 2

Note: Scheduling is timed to start on a Monday.

Targeted therapy

• Alemtuzumab (Campath) as follows:
  • Cycle 1: 3 mg IV once on day 1, then 10 mg IV once on day 2, then 30 mg IV once per day on days 3 & 5
  • Cycles 2 to 12: 30 mg IV once per day on days 1, 3, 5 or 2, 4, 6 (three times per week)

Supportive therapy

• Antibacterial prophylaxis: Trimethoprim-Sulfamethoxazole (Bactrim DS) 160/80 mg PO three times per week
• Antiviral prophylaxis: Famciclovir (Famvir) or Valganciclovir (Valcyte) once per day
• Antifungal prophylaxis: Fluconazole (Diflucan)

7-day cycle for up to 12 cycles

References

1. Sharma K, Janik JE, O'Mahony D, Stewart D, Pittaluga S, Stetler-Stevenson M, Jaffe ES, Raffeld M, Fleisher TA, Lee CC, Steinberg SM, Waldmann TA, Morris JC. Phase II study of alemtuzumab (CAMPATH-1) in patients with HTLV-1-associated adult T-cell leukemia/lymphoma. Clin Cancer Res. 2017 Jan 1;23(1):35-42. Epub 2016 Aug 2. link to original article link to PMC article contains dosing details in manuscript PubMed

Lenalidomide monotherapy

Regimen

Study	Dates of enrollment	Evidence	Efficacy
Ishida et al. 2016 (ATLL-002)	2012-2014	Phase 2	ORR: 42% (95% CI 23-63)

Targeted therapy

• Lenalidomide (Revlimid) 25 mg PO once per day

Continued indefinitely

References

1. ATLL-002: Ishida T, Fujiwara H, Nosaka K, Taira N, Abe Y, Imaizumi Y, Moriuchi Y, Jo T, Ishizawa K, Tobinai K, Tsukasaki K, Ito S, Yoshimitsu M, Otsuka M, Ogura M, Midorikawa S, Ruiz W, Ohtsu T. Multicenter phase II study of lenalidomide in relapsed or recurrent adult T-cell leukemia/lymphoma: ATLL-002. J Clin Oncol. 2016 Dec;34(34):4086-4093. Epub 2016 Sep 30. link to original article contains dosing details in manuscript PubMed NCT01724177

Valemetostat monotherapy

Regimen

Study	Dates of enrollment	Evidence
Izutsu et al. 2022 (DS3201-A-J201)	2019-11 to 2020-10	Phase 2 (RT)

Targeted therapy

• Valemetostat (Ezharmia) 200 mg PO once per day on days 1 to 28, taken at least 2 hours before or at least 1 hour after a meal

28-day cycles

References

1. DS3201-A-J201: Izutsu K, Makita S, Nosaka K, Yoshimitsu M, Utsunomiya A, Kusumoto S, Morishima S, Tsukasaki K, Kawamata T, Ono T, Rai S, Katsuya H, Ishikawa J, Yamada H, Kato K, Tachibana M, Kakurai Y, Adachi N, Tobinai K, Yonekura K, Ishitsuka K. An open-label, single-arm phase 2 trial of valemetostat for relapsed or refractory adult T-cell leukemia/lymphoma. Blood. 2023 Mar 9;141(10):1159-1168. Epub 2022 Sep 27. link to original article link to PMC article contains dosing details in manuscript PubMed NCT04102150