Anaplastic large cell lymphoma

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Note: these studies were specific to ALCL or had ALCL subgroups; regimens used in PTCL, NOS are also often used in this condition. Certain regimens have been moved to dedicated pages:
*Pediatric ALCL
Last updated on 2024-12-02:9 regimens on this page
11 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==
*2015: d'Amore et al. Peripheral T-cell lymphomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up EuroPMC
==NCCN==
*NCCN does not currently have guidelines at this granular level; please see NCCN Guidelines - T-cell Lymphomas.
=Untreated=
==BV-CHP==
BV-CHP: 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 	Longer PFS (primary endpoint)Median PFS: 48.2 vs 20.8 mo(HR 0.71, 95% CI 0.54-0.93)Longer OS (secondary endpoint)Median OS: NYR vs NYR(HR 0.66, 95% CI 0.46-0.95)
====Antibody-drug conjugate therapy====
*Brentuximab vedotin (Adcetris) 1.8 mg/kg (maximum dose of 180 mg) IV once on day 1
====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===
# 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 dosing details in abstract have been reviewed by our editors link to PMC article EuroPMC NCT01777152
==CHOEP-14==
CHOEP-14: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Etoposide, Prednisone every 14 days
CHOPE
VACOP
===Example orders===
*Example orders for CHOEP in lymphoma
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy 	Comparative Toxicity
Pfreundschuh et al. 2004 (NHL-B1)	1993-2000 	Phase 3, fewer than 20 pts in this subgroup (E-esc)	1. CHOEP-212. CHOP-21 3. CHOP-14	Not reported by subgroup	Not reported by subgroup
Note: This regimen was used in 16 patients with ALCL in the NHL-B1 trial. The authors did not report a subgroup analysis for this minority population.
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
*Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
*Vincristine (Oncovin) 2 mg IV once on day 1
*Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
====Glucocorticoid therapy====
*Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
====Supportive therapy====
*Filgrastim (Neupogen) by the following weight-based criteria:
**Less than 75 kg: 300 mcg SC once per day on days 4 to 13
**75 kg or more: 480 mcg SC once per day on days 4 to 13
14-day cycle for 6 cycles; next cycle to start as long as WBC count is greater than 2.5 x 109/L and platelets greater than 80 x 109/L
====Subsequent treatment====
*NHL-B1, patients with initial bulky disease (mass conglomerate at least 7.5 cm): RT consolidation x 3600 cGy to extranodal sites of disease when possible
===References===
# NHL-B1: Pfreundschuh M, Trümper L, Kloess M, Schmits R, Feller AC, Rudolph C, Reiser M, Hossfeld DK, Metzner B, Hasenclever D, Schmitz N, Glass B, Rübe C, Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of young patients with good-prognosis (normal LDH) aggressive lymphomas: results of the NHL-B1 trial of the DSHNHL. Blood. 2004 Aug 1;104(3):626-33. Epub 2004 Feb 24. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==CHOEP-21==
CHOEP-21: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Etoposide, Prednisone every 21 days
CHOPE
VACOP
===Example orders===
*Example orders for CHOEP in lymphoma
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy 	Comparative Toxicity
Pfreundschuh et al. 2004 (NHL-B1)	1993-2000 	Phase 3, fewer than 20 pts in this subgroup (E-esc)	1. CHOEP-142. CHOP-213. CHOP-14	Not reported by subgroup	Not reported by subgroup
Note: This regimen was used in 20 patients with ALCL in the NHL-B1 trial. The authors did not report a subgroup analysis for this minority population.
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
*Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
*Vincristine (Oncovin) 2 mg IV once on day 1
*Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
====Glucocorticoid therapy====
*Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
====Supportive therapy====
*Filgrastim (Neupogen) is by discretion of ordering physician
21-day cycle for 6 cycles; next cycle to start as long as WBC count is greater than 2.5 x 109/L and platelets greater than 80 x 109/L
====Subsequent treatment====
*NHL-B1, patients with initial bulky disease (mass conglomerate at least 7.5 cm): RT consolidation x 3600 cGy to extranodal sites of disease when possible
===References===
# NHL-B1: Pfreundschuh M, Trümper L, Kloess M, Schmits R, Feller AC, Rudolph C, Reiser M, Hossfeld DK, Metzner B, Hasenclever D, Schmitz N, Glass B, Rübe C, Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of young patients with good-prognosis (normal LDH) aggressive lymphomas: results of the NHL-B1 trial of the DSHNHL. Blood. 2004 Aug 1;104(3):626-33. Epub 2004 Feb 24. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==CHOP==
CHOP: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone
CHOP-21
ACOP
CAVP
COPA
VACP
VCAP
===Regimen variant #1, capped vincristine===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Horwitz et al. 2018 (ECHELON-2)	2013-2016 	Phase 3 (C)	BV-CHP 	Shorter OS
====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
21-day cycle for 6 to 8 cycles
===Regimen variant #2, flat-dose vincristine===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy 	Comparative Toxicity
Pfreundschuh et al. 2004 (NHL-B1)	1993-2000 	Phase 3, fewer than 20 pts in this subgroup (C)	1. CHOEP-142. CHOEP-213. CHOP-14	Not reported by subgroup	Not reported by subgroup
Note: This regimen was used in 14 patients with ALCL in NHL-B1. The authors did not report a subgroup analysis for this minority population.
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
*Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
*Vincristine (Oncovin) 2 mg IV once on day 1
====Glucocorticoid therapy====
*Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
====Supportive therapy====
*At the discretion of ordering physician: Filgrastim (Neupogen) by the following weight-based criteria:
**Less than 75 kg: 300 mcg SC once per day on days 4 to 13
**75 kg or more: 480 mcg SC once per day on days 4 to 13 
21-day cycle for 6 cycles
===References===
# NHL-B1: Pfreundschuh M, Trümper L, Kloess M, Schmits R, Feller AC, Rudolph C, Reiser M, Hossfeld DK, Metzner B, Hasenclever D, Schmitz N, Glass B, Rübe C, Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of young patients with good-prognosis (normal LDH) aggressive lymphomas: results of the NHL-B1 trial of the DSHNHL. Blood. 2004 Aug 1;104(3):626-33. Epub 2004 Feb 24. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 dosing details in abstract have been reviewed by our editors link to PMC article EuroPMC NCT01777152
==DA-EPOCH==
DA-EPOCH: Dose Adjusted Etoposide, Prednisone, Oncovin (Vincristine), Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin)
===Regimen===
Study 	Dates of enrollment	Evidence
Dunleavy et al. 2015 (NCI 93-C-0133ALCL)	1993-2009 	Phase 2
Note: this should be considered a substudy under the master protocol NCI 93-C-0133.
====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 PO twice per day on days 1 to 5
====Supportive therapy====
*Filgrastim (Neupogen) 300 mcg SC once per day, starting on day 6 and continuing until ANC greater than 5000/μL past nadir
*Trimethoprim-Sulfamethoxazole (Bactrim DS) 160/800 mg (or equivalent if allergic) PO once per day on 3 days per week
*Omeprazole (Prilosec) 20 mg (or equivalent) PO once per day
*Docusate (Colace) (dose not specified) and Sennosides (Senna) 2 tablets PO twice per day as needed for constipation
*Lactulose 20 g PO every 6 hours as needed for constipation
*Hepatitis B surface antigen positive patients: received daily antiviral therapy until 8 weeks after completion of chemotherapy
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 one level (20%) compared to previous cycle.
*If nadir ANC less than 500/μL, use same doses as last cycle.
*If nadir platelet count less than 25 x 109/L, decrease etoposide, doxorubicin, and cyclophosphamide by 20% compared to the previous cycle.
===References===
# NCI 93-C-0133ALCL: Dunleavy K, Pittaluga S, Shovlin M, Roschewski M, Lai C, Steinberg SM, Jaffe ES, Wilson WH. Phase II trial of dose-adjusted EPOCH in untreated systemic anaplastic large cell lymphoma. Haematologica. 2016 Jan;101(1):e27-9. Epub 2015 Oct 30. link to original article refers to protocol in Dunleavy et al. 2013 link to PMC article EuroPMC NCT00001337
=Relapsed or refractory, salvage therapy=
==Brentuximab vedotin monotherapy==
===Regimen===
Study 	Dates of enrollment 	Evidence
Gopal et al. 2012 (SGN35-006)	2009 to not reported	Phase 2, fewer than 20 pts in subgroup
Pro et al. 2012 (SG035-0004) 	2009-2010 	Phase 2 (RT)
Gibb et al. 2012 	2010-12 to 2011-08 	Named Patient Programme
Note: SGN35-006 is a re-treatment trial; all patients were previously exposed to brentuximab vedotin. Patients who had received the 1.2 mg/kg dose on a prior trial also received that dose at re-treatment.
====Antibody-drug conjugate therapy====
*Brentuximab vedotin (Adcetris) 1.8 mg/kg IV over 30 minutes once on day 1
21-day cycle for varying durations: 16 cycles (SG035-0004); until transplant (Gibb et al. 2012); indefinitely (SGN35-006)
===References===
# SGN35-006: Gopal AK, Ramchandren R, O'Connor OA, Berryman RB, Advani RH, Chen R, Smith SE, Cooper M, Rothe A, Matous JV, Grove LE, Zain J. Safety and efficacy of brentuximab vedotin for Hodgkin lymphoma recurring after allogeneic stem cell transplantation. Blood. 2012 Jul 19;120(3):560-8. Epub 2012 Apr 17. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT00947856
## Update: Bartlett NL, Chen R, Fanale MA, Brice P, Gopal A, Smith SE, Advani R, Matous JV, Ramchandren R, Rosenblatt JD, Huebner D, Levine P, Grove L, Forero-Torres A. Retreatment with brentuximab vedotin in patients with CD30-positive hematologic malignancies. J Hematol Oncol. 2014 Mar 19;7:24. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC
# SG035-0004: Pro B, Advani R, Brice P, Bartlett NL, Rosenblatt JD, Illidge T, Matous J, Ramchandren R, Fanale M, Connors JM, Yang Y, Sievers EL, Kennedy DA, Shustov A. Brentuximab vedotin (SGN-35) in patients with relapsed or refractory systemic anaplastic large-cell lymphoma: results of a phase II study. J Clin Oncol. 2012 Jun 20;30(18):2190-6. Epub 2012 May 21. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00866047
## Update: Pro B, Advani R, Brice P, Bartlett NL, Rosenblatt JD, Illidge T, Matous J, Ramchandren R, Fanale M, Connors JM, Fenton K, Huebner D, Pinelli JM, Kennedy DA, Shustov A. Five-year results of brentuximab vedotin in patients with relapsed or refractory systemic anaplastic large cell lymphoma. Blood. 2017 Dec 21;130(25):2709-2717. Epub 2017 Oct 3. link to original article link to PMC article EuroPMC
# Gibb A, Jones C, Bloor A, Kulkarni S, Illidge T, Linton K, Radford J. Brentuximab vedotin in refractory CD30+ lymphomas: a bridge to allogeneic transplantation in approximately one quarter of patients treated on a Named Patient Programme at a single UK center. Haematologica. 2013 Apr;98(4):611-4. Epub 2012 Oct 12. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC
# Retrospective: Gopal AK, Bartlett NL, Forero-Torres A, Younes A, Chen R, Friedberg JW, Matous JV, Shustov AR, Smith SE, Zain J, O'Meara MM, Fanale MA. Brentuximab vedotin in patients aged 60 years or older with relapsed or refractory CD30-positive lymphomas: a retrospective evaluation of safety and efficacy. Leuk Lymphoma. 2014 Oct;55(10):2328-34. Epub 2014 Feb 24. link to original article EuroPMC
==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, <20 in this arm (C)	GDP 	Non-inferior ORR
====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===
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT00078949
==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, fewer than 20 pts in this arm (E-switch-ic)	DHAP 	Non-inferior ORR (co-primary endpoint)
====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===
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT00078949
=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
===Regimen variant #2, intravenous===
Study 	Dates of enrollment 	Evidence
Glass et al. 2014 (DSHNHL R3)	2004-06-16 to 2009-03-24	Phase 2
===References===
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT00785330
Category:Anaplastic large cell lymphoma regimens
Category:Disease-specific pages
Category:T-cell lymphomas