Adult T-cell leukemia-lymphoma

Section editor
	Bhagirathbhai Dholaria, MBBS Vanderbilt University Nashville, TN

5 regimens on this page 5 variants on this page

Guidelines

"How I Treat"

• 2021: Cook & Phillips How I treat adult T-cell leukemia/lymphoma

NCCN

• NCCN Guidelines - T-cell Lymphomas

Untreated

CHOP-14

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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	Years of enrollment	Evidence	Comparator	Comparative Efficacy	Comparative Toxicity
Itoh et al. 2002 (JCOG 9505)	1995-1998	Randomized Phase II (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 III (C)	mLSG15	Seems to have inferior CR rate	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
• Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5

Supportive medications

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

14-day cycle for 8 cycles

Intrathecal component

Intrathecal triple-therapy was given during recovery phase of cycles 1, 3, and 5 after platelet count was greater than 70 × 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 verified protocol PubMed NCT00145002

Interferon alfa-2b & Zidovudine

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Regimen

Study	Years of enrollment	Evidence
Gill et al. 1995	NR	Non-randomized, <20 pts

Of historic interest.

Immunotherapy

• Interferon alfa-2b (Intron-A)
• Zidovudine (Retrovir)

References

1. Gill PS, Harrington W Jr, Kaplan MH, Ribeiro RC, Bennett JM, Liebman HA, Bernstein-Singer M, Espina BM, Cabral L, Allen S, Kornblau S, Pike MC, Levine AM. Treatment of adult T-cell leukemia-lymphoma with a combination of interferon alfa and zidovudine. N Engl J Med. 1995 Jun 29;332(26):1744-8. link to original article PubMed

LSG15

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Regimen

Study	Years of enrollment	Evidence
Yamada et al. 2001 (JCOG 9303)	1994-1996	Phase II

Ranimustine is not available in the United States and is approved only in Japan. This regimen was notable for excess CNS relapses and was subsequently replaced by mLSG15.

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

28-day cycle for 7 cycles

References

1. JCOG 9303: Yamada Y, Tomonaga M, Fukuda H, Hanada S, Utsunomiya A, Tara M, Sano M, Ikeda S, Takatsuki K, Kozuru M, Araki K, Kawano F, Niimi M, Tobinai K, Hotta T, Shimoyama M. A new G-CSF-supported combination chemotherapy, LSG15, for adult T-cell leukaemia-lymphoma: Japan Clinical Oncology Group Study 9303. Br J Haematol. 2001 May;113(2):375-82. link to original article PubMed

mLSG15

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Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Tsukasaki et al. 2007 (JCOG 9801)	1998-2003	Phase III (E-esc)	CHOP-14	Seems to have superior CR rate
Ishida et al. 2015 (Kyowa 0761-003)	2010-2011	Randomized Phase II (C)	mLSG15 & Mogamulizumab	Did not meet primary endpoint of CR rate

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

28-day cycle for 6 cycles

CNS 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 × 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 verified protocol 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

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Regimen

Study	Years of enrollment	Evidence
Sharma et al. 2016	2004-2009	Phase II

Targeted therapy

• Alemtuzumab (Campath) 30 mg IV once per day on days 1, 3, 5 (three times per week)

7-day cycle for up to 7 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 contain protocol link to PMC article PubMed

Lenalidomide monotherapy

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Regimen

Study	Years of enrollment	Evidence	Efficacy
Ishida et al. 2016 (ATLL-002)	2012-2014	Phase II	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. link to original article PubMed NCT01724177