Revision as of 12:12, 29 October 2022

11 regimens on this page 11 variants on this page

Note: these regimens have been studied specifically in primary mediastinal B-cell lymphoma. Other large B-cell lymphoma regimens, such as those used in diffuse large B-cell lymphoma are also often used.

Guidelines

BSH

2019: Cwynarski et al. The management of primary mediastinal B-cell lymphoma: a British Society for Haematology Good Practice Paper

ESMO

2016: Vitolo et al. Extranodal diffuse large B-cell lymphoma (DLBCL) and primary mediastinal B-cell lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed

Older

2013: ESMO Guidelines consensus conference on malignant lymphoma 2011 part 1: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL) PubMed

NCCN

NCCN Guidelines - B-cell Lymphomas

Untreated

DA-R-EPOCH

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

Regimen

Study	Years of enrollment	Evidence
Dunleavy et al. 2013 (NCI 93-C-0133)	1999-2012	Phase 2
Purroy et al. 2014	2002-2008	Phase 2, <20 pts in this subgroup

Targeted therapy

Rituximab (Rituxan) 375 mg/m² IV over 3 hours once on day 1

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; dose was not capped)
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 5,000/uL past nadir
Trimethoprim-Sulfamethoxazole (Bactrim DS) 160/800 mg (or equivalent if allergic) PO once per day on 3 days per week
- Note: It's assumed this is what the supplement for Dunleavy et al. 2013 meant by "Baxtrim (sulphametoxazole and trimethoprim)"
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 modifications

Start cycle 1 as described above.
Obtain CBCs twice per week for nadir measurements.
If nadir ANC greater than 500, increase etoposide, doxorubicin, and cyclophosphamide by one level (20%) compared to previous cycle.
If nadir ANC less than 500, use same doses as last cycle.
If nadir platelet count less than 25,000, decrease etoposide, doxorubicin, and cyclophosphamide by 20% compared to the previous cycle.

References

NCI 93-C-0133: Dunleavy K, Pittaluga S, Maeda LS, Advani R, Chen CC, Hessler J, Steinberg SM, Grant C, Wright G, Varma G, Staudt LM, Jaffe ES, Wilson WH. Dose-adjusted EPOCH-rituximab therapy in primary mediastinal B-cell lymphoma. N Engl J Med. 2013 Apr 11;368(15):1408-16. link to original article link to supplementary appendix link to PMC article contains dosing details in manuscript PubMed NCT00001337
Purroy N, Bergua J, Gallur L, Prieto J, Lopez LA, Sancho JM, García-Marco JA, Castellví J, Montes-Moreno S, Batlle A, de Villambrosia SG, Carnicero F, Ferrando-Lamana L, Piris MA, Lopez A. Long-term follow-up of dose-adjusted EPOCH plus rituximab (DA-EPOCH-R) in untreated patients with poor prognosis large B-cell lymphoma: a phase II study conducted by the Spanish PETHEMA group. Br J Haematol. 2015 Apr;169(2):188-98. Epub 2014 Dec 18. link to original article PubMed EudraCT 2004-001684-22

R-CHOP

R-CHOP: Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone
R-CHOP-21
CHOP-R

Example orders

Example orders for R-CHOP in lymphoma

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Pfreundschuh et al. 2006 (NCIC-CTG LY.9)	2000-2003	Phase 3 (E-esc)	1. CHOP 2. CHOEP 3. MACOP-B 4. PMitCEBO	Seems to have superior EFS

Targeted therapy

Rituximab (Rituxan) 375 mg/m² 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
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

G-CSF with one of the following:
- Filgrastim (Neupogen) used at physician discretion for neutropenia
- Lenograstim (Granocyte) used at physician discretion for neutropenia

21-day cycle for 6 cycles

Subsequent treatment

Radiation therapy

References

NCIC-CTG LY.9: Pfreundschuh M, Trümper L, Osterborg A, Pettengell R, Trneny M, Imrie K, Ma D, Gill D, Walewski J, Zinzani PL, Stahel R, Kvaloy S, Shpilberg O, Jaeger U, Hansen M, Lehtinen T, López-Guillermo A, Corrado C, Scheliga A, Milpied N, Mendila M, Rashford M, Kuhnt E, Loeffler M; MabThera International Trial Group. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006 May;7(5):379-91. link to original article contains dosing details in manuscript PubMed
1. Subgroup analysis: Rieger M, Osterborg A, Pettengell R, White D, Gill D, Walewski J, Kuhnt E, Loeffler M, Pfreundschuh M, Ho AD; MabThera International Trial (MInT) Group. Primary mediastinal B-cell lymphoma treated with CHOP-like chemotherapy with or without rituximab: results of the Mabthera International Trial Group study. Ann Oncol. 2011 Mar;22(3):664-70. Epub 2010 Aug 19. link to original article PubMed

R-CHOP (Prednisolone)

R-CHOP: Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisolone

Example orders

Example orders for R-CHOP in lymphoma

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Cunningham et al. 2013 (UK NCRI R-CHOP14v21)	2005-2008	Phase 3 (C)	R-CHOP-14	Might have inferior OS¹

¹Reported efficacy is based on a post-hoc subgroup analysis.

Targeted therapy

Rituximab (Rituxan) 375 mg/m² 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
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 1

Glucocorticoid therapy

Prednisolone (Millipred) 40 mg/m² PO once per day on days 1 to 5

CNS therapy, prophylaxis

Per investigator discretion, but Cunningham et al. 2013 recommended that patients who had involvement of the "bone marrow, peripheral blood, nasal or paranasal sinuses, orbit, and testis" (they probably intended to say "or testis") receive:

Methotrexate (MTX) 12.5 mg IT "for the first three cycles of treatment, administered as per local guidelines." No other details given.

Supportive therapy

Lenograstim (Granocyte) (dose/route not specified) given on days 4 to 12 at physician discretion
Allopurinol (Zyloprim) 300 mg PO once per day during cycle 1
Co-trimoxazole 80/400 mg PO twice per day on 3 days per week, taken throughout therapy, ending 2 weeks after chemotherapy is completed

21-day cycle for 8 cycles

References

UK NCRI R-CHOP14v21: Cunningham D, Hawkes EA, Jack A, Qian W, Smith P, Mouncey P, Pocock C, Ardeshna KM, Radford JA, McMillan A, Davies J, Turner D, Kruger A, Johnson P, Gambell J, Linch D. Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone in patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphoma: a phase 3 comparison of dose intensification with 14-day versus 21-day cycles. Lancet. 2013 May 25;381(9880):1817-26. Epub 2013 Apr 22. link to original article contains dosing details in manuscript PubMed ISRCTN16017947
1. Subgroup analysis: Gleeson M, Hawkes EA, Cunningham D, Chadwick N, Counsell N, Lawrie A, Jack A, Smith P, Mouncey P, Pocock C, Ardeshna KM, Radford J, McMillan A, Davies J, Turner D, Kruger A, Johnson PW, Gambell J, Linch D. Rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) in the management of primary mediastinal B-cell lymphoma: a subgroup analysis of the UK NCRI R-CHOP 14 versus 21 trial. Br J Haematol. 2016 Nov;175(4):668-672. Epub 2016 Aug 1. link to original article PubMed

R-CHOP-14 (Prednisolone)

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

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Cunningham et al. 2013 (UK NCRI R-CHOP14v21)	2005-2008	Phase 3 (E-esc)	R-CHOP-21	Might have superior OS¹

¹Reported efficacy is based on the 2016 subgroup analysis.

Targeted therapy

Rituximab (Rituxan) 375 mg/m² 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
Vincristine (Oncovin) 2 mg IV once on day 1

Glucocorticoid therapy

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

CNS therapy, prophylaxis

Per investigator discretion, but Cunningham et al. 2013 recommended that patients who had involvement of the "bone marrow, peripheral blood, nasal or paranasal sinuses, orbit, and testis" (they probably intended to say "or testis") receive:

Methotrexate (MTX) 12.5 mg IT "for the first three cycles of treatment, administered as per local guidelines." No other details given.

Supportive therapy

Lenograstim (Granocyte) (dose/route not specified) given on days 4 to 12
Allopurinol (Zyloprim) 300 mg PO once per day during cycle 1
Co-trimoxazole 480 mg (route not specified) twice per day on 3 days per week, taken throughout therapy, ending 2 weeks after treatment is completed

14-day cycle for 6 cycles (8 cycles of rituximab)

References

UK NCRI R-CHOP14v21: Cunningham D, Hawkes EA, Jack A, Qian W, Smith P, Mouncey P, Pocock C, Ardeshna KM, Radford JA, McMillan A, Davies J, Turner D, Kruger A, Johnson P, Gambell J, Linch D. Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone in patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphoma: a phase 3 comparison of dose intensification with 14-day versus 21-day cycles. Lancet. 2013 May 25;381(9880):1817-26. Epub 2013 Apr 22. link to original article contains dosing details in manuscript PubMed ISRCTN16017947
1. Subgroup analysis: Gleeson M, Hawkes EA, Cunningham D, Chadwick N, Counsell N, Lawrie A, Jack A, Smith P, Mouncey P, Pocock C, Ardeshna KM, Radford J, McMillan A, Davies J, Turner D, Kruger A, Johnson PW, Gambell J, Linch D. Rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) in the management of primary mediastinal B-cell lymphoma: a subgroup analysis of the UK NCRI R-CHOP 14 versus 21 trial. Br J Haematol. 2016 Nov;175(4):668-672. Epub 2016 Aug 1. link to original article PubMed

Consolidation after upfront therapy

Radiation therapy

Regimen

Study	Evidence
Pfreundschuh et al. 2006 (NCIC-CTG LY.9)	Non-randomized portion of RCT

Preceding treatment

CHOP x 6 or CHOEP-21 x 6 or PMitCEBO x 6 or MACOP-B x 6 versus R-CHOP x 6 or R-CHOEP-21 x 6 or R-PMitCEBO x 6 or R-MACOP-B x 6

Radiotherapy

External beam radiotherapy: 30 to 40 Gy given to sites of primary bulky disease; 30 to 40 Gy to primary extranodal disease at physician discretion

References

NCIC-CTG LY.9: Pfreundschuh M, Trümper L, Osterborg A, Pettengell R, Trneny M, Imrie K, Ma D, Gill D, Walewski J, Zinzani PL, Stahel R, Kvaloy S, Shpilberg O, Jaeger U, Hansen M, Lehtinen T, López-Guillermo A, Corrado C, Scheliga A, Milpied N, Mendila M, Rashford M, Kuhnt E, Loeffler M; MabThera International Trial Group. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006 May;7(5):379-91. link to original article contains dosing details in manuscript PubMed NCT00064116
1. Subgroup analysis: Rieger M, Osterborg A, Pettengell R, White D, Gill D, Walewski J, Kuhnt E, Loeffler M, Pfreundschuh M, Ho AD; MabThera International Trial (MInT) Group. Primary mediastinal B-cell lymphoma treated with CHOP-like chemotherapy with or without rituximab: results of the Mabthera International Trial Group study. Ann Oncol. 2011 Mar;22(3):664-70. Epub 2010 Aug 19. link to original article PubMed

Relapsed or refractory, salvage therapy

R-DHAP

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

Regimen

Study	Evidence	Comparator
Crump et al. 2014 (NCIC-CTG LY.12)	Phase 3, <20 pts in subgroup (C)	R-GDP

Targeted therapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1

Glucocorticoid therapy

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

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

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 contains dosing details in manuscript PubMed NCT00078949

R-GDP

R-GDP: Rituximab, Gemcitabine, Dexamethasone, Platinol (Cisplatin)

Regimen

Study	Evidence	Comparator
Crump et al. 2014 (NCIC-CTG LY.12)	Phase 3, <20 pts in subgroup (E-switch-ic)	R-DHAP

Targeted therapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1

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 contains dosing details in manuscript PubMed NCT00078949

Consolidation after salvage therapy

FluBuCy, then allo HSCT

FluBuCy: Fludarabine, Busulfan, Cyclophosphamide

Regimen

Study	Evidence
Glass et al. 2014 (DSHNHL R3)	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

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 link to original protocol (in German) contains dosing details in manuscript PubMed NCT00785330

Relapsed or refractory, further lines of therapy

Axicabtagene ciloleucel monotherapy

Regimen

FDA-recommended dose

Study	Years of enrollment	Evidence	Efficacy
Locke et al. 2017 (ZUMA-1)	2015-2016	Phase 1/2, <20 pts in subgroup (RT)	ORR: 82%

Preceding treatment

Lymphodepletion with FC

Immunotherapy

Axicabtagene ciloleucel (Yescarta) target dose of 2 × 10⁶ CAR T cells/kg IV once on day 0

Supportive therapy

Acetaminophen (Tylenol) 650 mg PO once on day 0, approximately 60 minutes prior to Axicabtagene ciloleucel (Yescarta)
Diphenhydramine (Benadryl) 12.5 mg IV or PO once on day 0, approximately 60 minutes prior to Axicabtagene ciloleucel (Yescarta)

One course; patients with initial response and disease progression at least 3 months later could be retreated

References

ZUMA-1: Locke FL, Neelapu SS, Bartlett NL, Siddiqi T, Chavez JC, Hosing CM, Ghobadi A, Budde LE, Bot A, Rossi JM, Jiang Y, Xue AX, Elias M, Aycock J, Wiezorek J, Go WY. Phase 1 results of ZUMA-1: A multicenter study of KTE-C19 anti-CD19 CAR T cell therapy in refractory aggressive lymphoma. Mol Ther. 2017 Jan 4;25(1):285-295. Epub 2017 Jan 4. link to original article link to PMC article PubMed NCT02348216
1. Update: Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, Braunschweig I, Oluwole OO, Siddiqi T, Lin Y, Timmerman JM, Stiff PJ, Friedberg JW, Flinn IW, Goy A, Hill BT, Smith MR, Deol A, Farooq U, McSweeney P, Munoz J, Avivi I, Castro JE, Westin JR, Chavez JC, Ghobadi A, Komanduri KV, Levy R, Jacobsen ED, Witzig TE, Reagan P, Bot A, Rossi J, Navale L, Jiang Y, Aycock J, Elias M, Chang D, Wiezorek J, Go WY. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017 Dec 28;377(26):2531-2544. Epub 2017 Dec 10. link to original article contains dosing details in manuscript link to PMC article PubMed
2. Update: Locke FL, Ghobadi A, Jacobson CA, Miklos DB, Lekakis LJ, Oluwole OO, Lin Y, Braunschweig I, Hill BT, Timmerman JM, Deol A, Reagan PM, Stiff P, Flinn IW, Farooq U, Goy A, McSweeney PA, Munoz J, Siddiqi T, Chavez JC, Herrera AF, Bartlett NL, Wiezorek JS, Navale L, Xue A, Jiang Y, Bot A, Rossi JM, Kim JJ, Go WY, Neelapu SS. Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1-2 trial. Lancet Oncol. 2019 Jan;20(1):31-42. Epub 2018 Dec 2. link to original article link to PMC article contains dosing details in manuscript PubMed

Lisocabtagene maraleucel monotherapy

Regimen

Study	Years of enrollment	Evidence
Abramson et al. 2020 (TRANSCEND NHL-001)	2016-2019	Phase 1 (RT)

Immunotherapy

Lisocabtagene maraleucel (Breyanzi)

References

TRANSCEND NHL-001: Abramson JS, Palomba ML, Gordon LI, Lunning MA, Wang M, Arnason J, Mehta A, Purev E, Maloney DG, Andreadis C, Sehgal A, Solomon SR, Ghosh N, Albertson TM, Garcia J, Kostic A, Mallaney M, Ogasawara K, Newhall K, Kim Y, Li D, Siddiqi T. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. Lancet. 2020 Sep 19;396(10254):839-852. Epub 2020 Sep 1. link to original article PubMed NCT02631044

Pembrolizumab monotherapy

Regimen

FDA-recommended dose

Study	Years of enrollment	Evidence
Armand et al. 2016 (KEYNOTE-013)	2014-2016	Phase 1b
Armand et al. 2016 (KEYNOTE-170)	2016-2017	Phase 2 (RT)

Immunotherapy

Pembrolizumab (Keytruda) 200 mg IV over 30 minutes once on day 1

21-day cycle for up to 35 cycles (2 years)

References

KEYNOTE-013: Armand P, Rodig S, Melnichenko V, Thieblemont C, Bouabdallah K, Tumyan G, Özcan M, Portino S, Fogliatto L, Caballero MD, Walewski J, Gulbas Z, Ribrag V, Christian B, Perini GF, Salles G, Svoboda J, Zain J, Patel S, Chen PH, Ligon AH, Ouyang J, Neuberg D, Redd R, Chatterjee A, Balakumaran A, Orlowski R, Shipp M, Zinzani PL. Pembrolizumab in Relapsed or Refractory Primary Mediastinal Large B-Cell Lymphoma. J Clin Oncol. 2019 Dec 1;37(34):3291-3299. Epub 2019 Oct 14. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01953692
KEYNOTE-170: Armand P, Rodig S, Melnichenko V, Thieblemont C, Bouabdallah K, Tumyan G, Özcan M, Portino S, Fogliatto L, Caballero MD, Walewski J, Gulbas Z, Ribrag V, Christian B, Perini GF, Salles G, Svoboda J, Zain J, Patel S, Chen PH, Ligon AH, Ouyang J, Neuberg D, Redd R, Chatterjee A, Balakumaran A, Orlowski R, Shipp M, Zinzani PL. Pembrolizumab in Relapsed or Refractory Primary Mediastinal Large B-Cell Lymphoma. J Clin Oncol. 2019 Dec 1;37(34):3291-3299. Epub 2019 Oct 14. link to original article contains dosing details in manuscript link to PMC article PubMed NCT02576990

@@ Line 14: / Line 14: @@
 ==BSH==
 *'''2019:''' Cwynarski et al. [https://doi.org/10.1111/bjh.15731 The management of primary mediastinal B-cell lymphoma: a British Society for Haematology Good Practice Paper]
 ==[http://www.esmo.org/ ESMO]==
 *'''2016:''' Vitolo et al. [http://annonc.oxfordjournals.org/content/27/suppl_5/v91.full.pdf+html Extranodal diffuse large B-cell lymphoma (DLBCL) and primary mediastinal B-cell lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/27377716 PubMed]
 ===Older===
 *'''2013:''' [http://annonc.oxfordjournals.org/content/24/3/561.full.pdf+html ESMO Guidelines consensus conference on malignant lymphoma 2011 part 1: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL)] [https://pubmed.ncbi.nlm.nih.gov/23175624 PubMed]
 ==[https://www.nccn.org/ NCCN]==
 *[https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf NCCN Guidelines - B-cell Lymphomas]
 =Untreated=
 ==DA-R-EPOCH {{#subobject:d7244e|Regimen=1}}==
 DA-R-EPOCH: '''<u>D</u>'''ose '''<u>A</u>'''djusted '''<u>R</u>'''ituximab, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>O</u>'''ncovin (Vincristine), '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin)
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:98dcb9|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 44: / Line 39: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Targeted therapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV over 3 hours once on day 1
@@ Line 61: / Line 57: @@
 *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 modifications====
 *Start cycle 1 as described above.
@@ Line 70: / Line 64: @@
 *If nadir ANC less than 500, use same doses as last cycle.
 *If nadir platelet count less than 25,000, decrease etoposide, doxorubicin, and cyclophosphamide by 20% compared to the previous cycle.
+</div></div>
 ===References===
 # '''NCI 93-C-0133:''' Dunleavy K, Pittaluga S, Maeda LS, Advani R, Chen CC, Hessler J, Steinberg SM, Grant C, Wright G, Varma G, Staudt LM, Jaffe ES, Wilson WH. Dose-adjusted EPOCH-rituximab therapy in primary mediastinal B-cell lymphoma. N Engl J Med. 2013 Apr 11;368(15):1408-16. [https://doi.org/10.1056/NEJMoa1214561 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1214561/suppl_file/nejmoa1214561_appendix.pdf link to supplementary appendix] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc4568999/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23574119 PubMed] NCT00001337
 # Purroy N, Bergua J, Gallur L, Prieto J, Lopez LA, Sancho JM, García-Marco JA, Castellví J, Montes-Moreno S, Batlle A, de Villambrosia SG, Carnicero F, Ferrando-Lamana L, Piris MA, Lopez A. Long-term follow-up of dose-adjusted EPOCH plus rituximab (DA-EPOCH-R) in untreated patients with poor prognosis large B-cell lymphoma: a phase II study conducted by the Spanish PETHEMA group. Br J Haematol. 2015 Apr;169(2):188-98. Epub 2014 Dec 18. [https://doi.org/10.1111/bjh.13273 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25521006 PubMed] EudraCT 2004-001684-22
 ==R-CHOP {{#subobject:796753|Regimen=1}}==
 R-CHOP: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone
 <br>R-CHOP-21
@@ Line 82: / Line 74: @@
 ===Example orders===
 *[[Example orders for R-CHOP in lymphoma]]
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:283715|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 98: / Line 90: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Targeted therapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
@@ Line 106: / Line 99: @@
 ====Glucocorticoid therapy====
 *[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 ====Supportive therapy====
 *G-CSF with one of the following:
 **[[Filgrastim (Neupogen)]] used at physician discretion for neutropenia
 **[[Lenograstim (Granocyte)]] used at physician discretion for neutropenia
 '''21-day cycle for 6 cycles'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
 *[[#Radiation_therapy|Radiation therapy]]
+</div></div>
 ===References===
 # '''NCIC-CTG LY.9:''' Pfreundschuh M, Trümper L, Osterborg A, Pettengell R, Trneny M, Imrie K, Ma D, Gill D, Walewski J, Zinzani PL, Stahel R, Kvaloy S, Shpilberg O, Jaeger U, Hansen M, Lehtinen T, López-Guillermo A, Corrado C, Scheliga A, Milpied N, Mendila M, Rashford M, Kuhnt E, Loeffler M; MabThera International Trial Group. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006 May;7(5):379-91. [https://doi.org/10.1016/S1470-2045%2806%2970664-7 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16648042 PubMed]
 ## '''Subgroup analysis:''' Rieger M, Osterborg A, Pettengell R, White D, Gill D, Walewski J, Kuhnt E, Loeffler M, Pfreundschuh M, Ho AD; MabThera International Trial (MInT) Group. Primary mediastinal B-cell lymphoma treated with CHOP-like chemotherapy with or without rituximab: results of the Mabthera International Trial Group study. Ann Oncol. 2011 Mar;22(3):664-70. Epub 2010 Aug 19. [https://doi.org/10.1093/annonc/mdq418 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20724576 PubMed]
 ==R-CHOP (Prednisolone) {{#subobject:7a9c53|Regimen=1}}==
 R-CHOP: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisolone
 ===Example orders===
 *[[Example orders for R-CHOP in lymphoma]]
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:74f424|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 142: / Line 133: @@
 |}
 ''<sup>1</sup>Reported efficacy is based on a post-hoc subgroup analysis.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Targeted therapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
@@ Line 150: / Line 142: @@
 ====Glucocorticoid therapy====
 *[[Prednisolone (Millipred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 5
 ====CNS therapy, prophylaxis====
 Per investigator discretion, but Cunningham et al. 2013 recommended that patients who had involvement of the "bone marrow, peripheral blood, nasal or paranasal sinuses, orbit, and testis" (they probably intended to say "or testis") receive:
 *[[Methotrexate (MTX)]] 12.5 mg IT "for the first three cycles of treatment, administered as per local guidelines." No other details given.
 ====Supportive therapy====
 *[[Lenograstim (Granocyte)]] (dose/route not specified) given on days 4 to 12 at physician discretion
 *[[Allopurinol (Zyloprim)]] 300 mg PO once per day during cycle 1
 *[[Trimethoprim-Sulfamethoxazole (Bactrim DS)|Co-trimoxazole]] 80/400 mg PO twice per day on 3 days per week, taken throughout therapy, ending 2 weeks after chemotherapy is completed
 '''21-day cycle for 8 cycles'''
+</div></div>
 ===References===
 # '''UK NCRI R-CHOP14v21:''' Cunningham D, Hawkes EA, Jack A, Qian W, Smith P, Mouncey P, Pocock C, Ardeshna KM, Radford JA, McMillan A, Davies J, Turner D, Kruger A, Johnson P, Gambell J, Linch D. Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone in patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphoma: a phase 3 comparison of dose intensification with 14-day versus 21-day cycles. Lancet. 2013 May 25;381(9880):1817-26. Epub 2013 Apr 22. [https://doi.org/10.1016/S0140-6736(13)60313-X link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23615461 PubMed] ISRCTN16017947
 ## '''Subgroup analysis:''' Gleeson M, Hawkes EA, Cunningham D, Chadwick N, Counsell N, Lawrie A, Jack A, Smith P, Mouncey P, Pocock C, Ardeshna KM, Radford J, McMillan A, Davies J, Turner D, Kruger A, Johnson PW, Gambell J, Linch D. Rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) in the management of primary mediastinal B-cell lymphoma: a subgroup analysis of the UK NCRI R-CHOP 14 versus 21 trial. Br J Haematol. 2016 Nov;175(4):668-672. Epub 2016 Aug 1. [https://onlinelibrary.wiley.com/wol1/doi/10.1111/bjh.14287 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27477167 PubMed]
 ==R-CHOP-14 (Prednisolone) {{#subobject:fc3bde|Regimen=1}}==
 R-CHOP-14: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisolone every '''<u>14</u>''' days
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:8136b1|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 185: / Line 173: @@
 |}
 ''<sup>1</sup>Reported efficacy is based on the 2016 subgroup analysis.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Targeted therapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
@@ Line 193: / Line 182: @@
 ====Glucocorticoid therapy====
 *[[Prednisolone (Millipred)]] 100 mg PO once per day on days 1 to 5
 ====CNS therapy, prophylaxis====
 Per investigator discretion, but Cunningham et al. 2013 recommended that patients who had involvement of the "bone marrow, peripheral blood, nasal or paranasal sinuses, orbit, and testis" (they probably intended to say "or testis") receive:
 *[[Methotrexate (MTX)]] 12.5 mg IT "for the first three cycles of treatment, administered as per local guidelines." No other details given.
 ====Supportive therapy====
 *[[Lenograstim (Granocyte)]] (dose/route not specified) given on days 4 to 12
 *[[Allopurinol (Zyloprim)]] 300 mg PO once per day during cycle 1
 *[[Trimethoprim-Sulfamethoxazole (Bactrim DS)|Co-trimoxazole]] 480 mg (route not specified) twice per day on 3 days per week, taken throughout therapy, ending 2 weeks after treatment is completed
 '''14-day cycle for 6 cycles (8 cycles of rituximab)'''
+</div></div>
 ===References===
 # '''UK NCRI R-CHOP14v21:''' Cunningham D, Hawkes EA, Jack A, Qian W, Smith P, Mouncey P, Pocock C, Ardeshna KM, Radford JA, McMillan A, Davies J, Turner D, Kruger A, Johnson P, Gambell J, Linch D. Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone in patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphoma: a phase 3 comparison of dose intensification with 14-day versus 21-day cycles. Lancet. 2013 May 25;381(9880):1817-26. Epub 2013 Apr 22. [https://doi.org/10.1016/S0140-6736(13)60313-X link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23615461 PubMed] ISRCTN16017947
 ## '''Subgroup analysis:''' Gleeson M, Hawkes EA, Cunningham D, Chadwick N, Counsell N, Lawrie A, Jack A, Smith P, Mouncey P, Pocock C, Ardeshna KM, Radford J, McMillan A, Davies J, Turner D, Kruger A, Johnson PW, Gambell J, Linch D. Rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) in the management of primary mediastinal B-cell lymphoma: a subgroup analysis of the UK NCRI R-CHOP 14 versus 21 trial. Br J Haematol. 2016 Nov;175(4):668-672. Epub 2016 Aug 1. [https://onlinelibrary.wiley.com/wol1/doi/10.1111/bjh.14287 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27477167 PubMed]
 =Consolidation after upfront therapy=
 ==Radiation therapy {{#subobject:89ce8b|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:952fa4|Variant=1}}===
 {| class="wikitable" style="width: 40%; text-align:center;"
@@ Line 220: / Line 206: @@
 |-
 |}
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *[[#CHOP|CHOP]] x 6 or [[#CHOEP-21|CHOEP-21]] x 6 or [[#PMitCEBO|PMitCEBO]] x 6 or [[#MACOP-B|MACOP-B]] x 6 versus [[#R-CHOP|R-CHOP]] x 6 or [[#R-CHOEP-21|R-CHOEP-21]] x 6 or [[#R-PMitCEBO|R-PMitCEBO]] x 6 or [[#R-MACOP-B|R-MACOP-B]] x 6
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Radiotherapy====
 *[[External beam radiotherapy]]: 30 to 40 Gy given to sites of primary bulky disease; 30 to 40 Gy to primary extranodal disease at physician discretion
+</div></div>
 ===References===
 # '''NCIC-CTG LY.9:''' Pfreundschuh M, Trümper L, Osterborg A, Pettengell R, Trneny M, Imrie K, Ma D, Gill D, Walewski J, Zinzani PL, Stahel R, Kvaloy S, Shpilberg O, Jaeger U, Hansen M, Lehtinen T, López-Guillermo A, Corrado C, Scheliga A, Milpied N, Mendila M, Rashford M, Kuhnt E, Loeffler M; MabThera International Trial Group. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006 May;7(5):379-91. [https://doi.org/10.1016/S1470-2045%2806%2970664-7 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16648042 PubMed] NCT00064116
 ## '''Subgroup analysis:''' Rieger M, Osterborg A, Pettengell R, White D, Gill D, Walewski J, Kuhnt E, Loeffler M, Pfreundschuh M, Ho AD; MabThera International Trial (MInT) Group. Primary mediastinal B-cell lymphoma treated with CHOP-like chemotherapy with or without rituximab: results of the Mabthera International Trial Group study. Ann Oncol. 2011 Mar;22(3):664-70. Epub 2010 Aug 19. [https://doi.org/10.1093/annonc/mdq418 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20724576 PubMed]
 =Relapsed or refractory, salvage therapy=
 ==R-DHAP {{#subobject:26123c|Regimen=1}}==
 R-DHAP: '''<u>R</u>'''ituximab, '''<u>D</u>'''examethasone, '''<u>H</u>'''igh-dose '''<u>A</u>'''ra-C (Cytarabine), '''<u>P</u>'''latinol (Cisplatin)
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:2ed78f|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 247: / Line 232: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Targeted therapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
@@ Line 254: / Line 240: @@
 *[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on day 2 (total dose per cycle: 4000 mg/m<sup>2</sup>)
 *[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1
 '''21-day cycle for up to 3 cycles'''
+</div></div>
 ===References===
 <!-- Presented in part at the Annual Meeting of the American Society of Hematology, Atlanta, GA, December 7-10, 2013, and the International Conference on Malignant Lymphoma, Lugano, Switzerland, June 19-22, 2013. -->
 # '''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. [https://doi.org/10.1200/jco.2013.53.9593 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25267740 PubMed] NCT00078949
 ==R-GDP {{#subobject:f6075a|Regimen=1}}==
 R-GDP: '''<u>R</u>'''ituximab, '''<u>G</u>'''emcitabine, '''<u>D</u>'''examethasone, '''<u>P</u>'''latinol (Cisplatin)
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:8091c0|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 275: / Line 259: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Targeted therapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
@@ Line 282: / Line 267: @@
 ====Glucocorticoid therapy====
 *[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4
 '''21-day cycle for up to 3 cycles'''
+</div></div>
 ===References===
 <!-- Presented in part at the Annual Meeting of the American Society of Hematology, Atlanta, GA, December 7-10, 2013, and the International Conference on Malignant Lymphoma, Lugano, Switzerland, June 19-22, 2013. -->
 # '''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. [https://doi.org/10.1200/jco.2013.53.9593 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25267740 PubMed] NCT00078949
 =Consolidation after salvage therapy=
 ==FluBuCy, then allo HSCT {{#subobject:84acb0|Regimen=1}}==
 FluBuCy: '''<u>Flu</u>'''darabine, '''<u>Bu</u>'''sulfan, '''<u>Cy</u>'''clophosphamide
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:bfe434|Variant=1}}===
 {| class="wikitable" style="width: 40%; text-align:center;"
@@ Line 303: / Line 286: @@
 |}
 {{#lst:Allogeneic HSCT|bfe434}}
-====Immunotherapy====
+</div></div>
-*[[Allogeneic stem cells]]
-'''Stem cells transfused on day 0'''
 ===References===
 <!-- # Glass B, rabbits Kamp 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. High-dose chemotherapy Followed by allogeneic stem cell transplantation in relapsed and refractory high-risk aggressive non-Hodgkin's lymphoma: Results of a prospective study of the German high-grade non-Hodgkin's lymphoma study group. J Clin Oncol 30, 2012 (suppl; abstr 8004) -->
 # '''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. [https://doi.org/10.1016/S1470-2045(14)70161-5 link to original article] [http://www.dshnhl.org/app/download/9495510598/Studienprotokoll+DSHNHL+alloFBC+final+vollst.pdf link to original protocol (in German)] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24827808 PubMed] NCT00785330
 =Relapsed or refractory, further lines of therapy=
 ==Axicabtagene ciloleucel monotherapy {{#subobject:78231d|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:e3e516|Variant=1}}===
 {| class="wikitable" style="color:white; background-color:#404040"
@@ Line 330: / Line 310: @@
 |-
 |}
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *Lymphodepletion with [[Autologous_HSCT#FC|FC]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Immunotherapy====
 *[[Axicabtagene ciloleucel (Yescarta)]] target dose of 2 × 10<sup>6</sup> CAR T cells/kg IV once on day 0
 ====Supportive therapy====
 *[[Acetaminophen (Tylenol)]] 650 mg PO once on day 0, approximately 60 minutes prior to [[Axicabtagene ciloleucel (Yescarta)]]
@@ Line 340: / Line 322: @@
 '''One course; patients with initial response and disease progression at least 3 months later could be retreated'''
+</div></div>
 ===References===
 #'''ZUMA-1:''' Locke FL, Neelapu SS, Bartlett NL, Siddiqi T, Chavez JC, Hosing CM, Ghobadi A, Budde LE, Bot A, Rossi JM, Jiang Y, Xue AX, Elias M, Aycock J, Wiezorek J, Go WY. Phase 1 results of ZUMA-1: A multicenter study of KTE-C19 anti-CD19 CAR T cell therapy in refractory aggressive lymphoma. Mol Ther. 2017 Jan 4;25(1):285-295. Epub 2017 Jan 4. [https://doi.org/10.1016/j.ymthe.2016.10.020 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5363293/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28129122 PubMed] NCT02348216
 ##'''Update:''' Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, Braunschweig I, Oluwole OO, Siddiqi T, Lin Y, Timmerman JM, Stiff PJ, Friedberg JW, Flinn IW, Goy A, Hill BT, Smith MR, Deol A, Farooq U, McSweeney P, Munoz J, Avivi I, Castro JE, Westin JR, Chavez JC, Ghobadi A, Komanduri KV, Levy R, Jacobsen ED, Witzig TE, Reagan P, Bot A, Rossi J, Navale L, Jiang Y, Aycock J, Elias M, Chang D, Wiezorek J, Go WY. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017 Dec 28;377(26):2531-2544. Epub 2017 Dec 10. [https://doi.org/10.1056/NEJMoa1707447 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5882485/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29226797 PubMed]
 ##'''Update:''' Locke FL, Ghobadi A, Jacobson CA, Miklos DB, Lekakis LJ, Oluwole OO, Lin Y, Braunschweig I, Hill BT, Timmerman JM, Deol A, Reagan PM, Stiff P, Flinn IW, Farooq U, Goy A, McSweeney PA, Munoz J, Siddiqi T, Chavez JC, Herrera AF, Bartlett NL, Wiezorek JS, Navale L, Xue A, Jiang Y, Bot A, Rossi JM, Kim JJ, Go WY, Neelapu SS. Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1-2 trial. Lancet Oncol. 2019 Jan;20(1):31-42. Epub 2018 Dec 2. [https://doi.org/10.1016/S1470-2045(18)30864-7 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6733402/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/30518502 PubMed]
 ==Lisocabtagene maraleucel monotherapy {{#subobject:6e6u14|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:6nvha6|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 360: / Line 340: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Immunotherapy====
 *[[Lisocabtagene maraleucel (Breyanzi)]]
+</div></div>
 ===References===
 #'''TRANSCEND NHL-001:''' Abramson JS, Palomba ML, Gordon LI, Lunning MA, Wang M, Arnason J, Mehta A, Purev E, Maloney DG, Andreadis C, Sehgal A, Solomon SR, Ghosh N, Albertson TM, Garcia J, Kostic A, Mallaney M, Ogasawara K, Newhall K, Kim Y, Li D, Siddiqi T. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. Lancet. 2020 Sep 19;396(10254):839-852. Epub 2020 Sep 1. [https://doi.org/10.1016/s0140-6736(20)31366-0 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32888407 PubMed] NCT02631044
 ==Pembrolizumab monotherapy {{#subobject:e0d17a|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:7b36e9|Variant=1}}===
 {| class="wikitable" style="color:white; background-color:#404040"
@@ Line 386: / Line 367: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Immunotherapy====
 *[[Pembrolizumab (Keytruda)]] 200 mg IV over 30 minutes once on day 1
 '''21-day cycle for up to 35 cycles (2 years)'''
+</div></div>
 ===References===
 <!-- # '''Abstract:''' J-M. Michot, P. Armand, W. Ding, V. Ribrag, B. Christian, A. Balakumaran, P. Marinello, S. Chlosta, Y. Zhang, M. Shipp, P.L. Zinzani; Pembrolizumab in patients with relapsed/refractory primary mediastinal large B-cell lymphoma (rrPMBCL) or relapsed or refractory Richter syndrome (rrRS): Phase 2 KEYNOTE-170 study, Annals of Oncology, Volume 27, Issue suppl_6, 1 October 2016, 944TiP. [https://academic.oup.com/annonc/article/27/suppl_6/944TiP/2799681 link to abstract] -->
 # '''KEYNOTE-013:''' Armand P, Rodig S, Melnichenko V, Thieblemont C, Bouabdallah K, Tumyan G, Özcan M, Portino S, Fogliatto L, Caballero MD, Walewski J, Gulbas Z, Ribrag V, Christian B, Perini GF, Salles G, Svoboda J, Zain J, Patel S, Chen PH, Ligon AH, Ouyang J, Neuberg D, Redd R, Chatterjee A, Balakumaran A, Orlowski R, Shipp M, Zinzani PL. Pembrolizumab in Relapsed or Refractory Primary Mediastinal Large B-Cell Lymphoma. J Clin Oncol. 2019 Dec 1;37(34):3291-3299. Epub 2019 Oct 14. [https://doi.org/10.1200/JCO.19.01389 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6881098/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31609651 PubMed] NCT01953692
 # '''KEYNOTE-170:''' Armand P, Rodig S, Melnichenko V, Thieblemont C, Bouabdallah K, Tumyan G, Özcan M, Portino S, Fogliatto L, Caballero MD, Walewski J, Gulbas Z, Ribrag V, Christian B, Perini GF, Salles G, Svoboda J, Zain J, Patel S, Chen PH, Ligon AH, Ouyang J, Neuberg D, Redd R, Chatterjee A, Balakumaran A, Orlowski R, Shipp M, Zinzani PL. Pembrolizumab in Relapsed or Refractory Primary Mediastinal Large B-Cell Lymphoma. J Clin Oncol. 2019 Dec 1;37(34):3291-3299. Epub 2019 Oct 14. [https://doi.org/10.1200/JCO.19.01389 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6881098/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31609651 PubMed] NCT02576990
 [[Category:Primary mediastinal B-cell lymphoma regimens]]
 [[Category:Disease-specific pages]]
 [[Category:Aggressive lymphomas]]
 [[Category:Non-Hodgkin lymphomas]]

Difference between revisions of "Primary mediastinal B-cell lymphoma"

Revision as of 12:12, 29 October 2022

Guidelines

BSH

ESMO

Older

NCCN

Untreated

DA-R-EPOCH

Regimen

Targeted therapy

Chemotherapy

Glucocorticoid therapy

Supportive therapy

Dose modifications

References

R-CHOP

Example orders

Regimen

Targeted therapy

Chemotherapy

Glucocorticoid therapy

Supportive therapy

Subsequent treatment

References

R-CHOP (Prednisolone)

Example orders

Regimen

Targeted therapy

Chemotherapy

Glucocorticoid therapy

CNS therapy, prophylaxis

Supportive therapy

References

R-CHOP-14 (Prednisolone)

Regimen

Targeted therapy

Chemotherapy

Glucocorticoid therapy

CNS therapy, prophylaxis

Supportive therapy

References

Consolidation after upfront therapy

Radiation therapy

Regimen

Preceding treatment

Radiotherapy

References

Relapsed or refractory, salvage therapy

R-DHAP

Regimen

Targeted therapy

Glucocorticoid therapy

Chemotherapy

References

R-GDP

Regimen

Targeted therapy

Chemotherapy

Glucocorticoid therapy

References

Consolidation after salvage therapy

FluBuCy, then allo HSCT

Regimen

Chemotherapy

Immunotherapy

GVHD prophylaxis

References

Relapsed or refractory, further lines of therapy

Axicabtagene ciloleucel monotherapy

Regimen

Preceding treatment

Immunotherapy

Supportive therapy

References

Lisocabtagene maraleucel monotherapy

Regimen

Immunotherapy

References

Pembrolizumab monotherapy