Anaplastic large cell lymphoma
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:
Section editor | |
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Bhagirathbhai Dholaria, MBBS Vanderbilt University Nashville, TN, USA |
Last updated on 2024-12-02: 9 regimens on this page
11 variants on this page
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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
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 | Superior PFS (primary endpoint) Median PFS: 48.2 vs 20.8 mo (HR 0.71, 95% CI 0.54-0.93) Superior 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 PubMed NCT01777152
CHOEP-14
CHOEP-14: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Etoposide, Prednisone every 14 days
CHOPE
VACOP
Example orders
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-21 2. 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 PubMed
CHOEP-21
CHOEP-21: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Etoposide, Prednisone every 21 days
CHOPE
VACOP
Example orders
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-14 2. CHOP-21 3. 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 PubMed
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 | Inferior 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-14 2. CHOEP-21 3. 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 PubMed
- 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 PubMed 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 PubMed 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 PubMed 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 PubMed
- 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 PubMed 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 PubMed
- 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 PubMed
- 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 PubMed
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 PubMed 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 PubMed 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 |
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
- 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 PubMed NCT00785330