Primary mediastinal B-cell lymphoma
Section editor | |
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J.C. Villasboas Bisneto, MD Mayo Clinic Rochester, MN |
11 regimens on this page
11 variants on this page
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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
Untreated
DA-R-EPOCH
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DA-R-EPOCH: Dose Adjusted Rituximab, Etoposide, Prednisone, Oncovin (Vincristine), Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin)
Regimen
Study | Evidence |
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Dunleavy et al. 2013 (NCI 93-C-0133) | Phase II |
Purroy et al. 2014 | Phase II, <20 pts in this subgroup |
Chemotherapy
- Rituximab (Rituxan) 375 mg/m2 IV over 3 hours once on day 1
- Etoposide (Vepesid) 50 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 200 mg/m2)
- Prednisone (Sterapred) 60 mg/m2 PO twice per day on days 1 to 5
- 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)
Supportive medications
- 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 adjustments
- 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 contains verified protocol PubMed
- 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
R-CHOP
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R-CHOP: Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone
R-CHOP-21
CHOP-R
Example orders
Regimen
Study | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|
Pfreundschuh et al. 2006 (NCIC CTG LY.9) | Phase III (E) | 1. CHOP 2. CHOEP 3. MACOP-B 4. PMitCEBO |
Seems to have superior EFS |
Chemotherapy
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
- 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
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
Supportive medications
- 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
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 verified protocol 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. link to original article PubMed
R-CHOP (Prednisolone)
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R-CHOP: Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisolone
Example orders
Regimen
Study | Evidence | Comparator | Comparative Efficacy |
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Cunningham et al. 2013 (UK NCRI R-CHOP14v21) | Phase III (C) | R-CHOP-14 | Might have inferior OS (*) |
Note: the efficacy reported here is based on a post-hoc subgroup analysis.
Chemotherapy
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
- 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
- Prednisolone (Millipred) 40 mg/m2 PO once per day on days 1 to 5
CNS 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 medications
- 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 verified protocol PubMed
- 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)
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R-CHOP-14: Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisolone every 14 days
Regimen
Study | Evidence | Comparator | Comparative Efficacy |
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Cunningham et al. 2013 (UK NCRI R-CHOP14v21) | Phase III (E) | R-CHOP-21 | Might have superior OS (*) |
Note: the efficacy reported here is based on a post-hoc subgroup analysis.
Chemotherapy
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
- 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
- Prednisolone (Millipred) 100 mg PO once per day on days 1 to 5
CNS 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 medications
- 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 verified protocol PubMed
- 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
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Regimen
Study | Evidence |
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Pfreundschuh et al. 2006 (NCIC CTG LY.9) | Non-randomized portion of RCT |
Preceding treatment
- CHOP-like therapy x 6 versus R-CHOP-like therapy (including R-CHOP) 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 verified protocol 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. link to original article PubMed
Relapsed or refractory, salvage therapy
R-DHAP
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R-DHAP: Rituximab, Dexamethasone, High-dose Ara-C (Cytarabine), Platinol (Cisplatin)
Regimen
Study | Evidence | Comparator |
---|---|---|
Crump et al. 2014 (NCIC-CTG LY.12) | Phase III, <20 pts in subgroup (C) | R-GDP |
Chemotherapy
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
- Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4
- 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
- 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 verified protocol PubMed
R-GDP
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R-GDP: Rituximab, Gemcitabine, Dexamethasone, Platinol (Cisplatin)
Regimen
Study | Evidence | Comparator |
---|---|---|
Crump et al. 2014 (NCIC-CTG LY.12) | Phase III, <20 pts in subgroup (E) | R-DHAP |
Chemotherapy
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
- Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4
- Cisplatin (Platinol) 75 mg/m2 IV once 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 verified protocol PubMed
Consolidation after salvage therapy
FluBuCy, then allo HSCT
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FluBuCy: Fludarabine, Busulfan, Cyclophosphamide
Regimen
Study | Evidence |
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Glass et al. 2014 (DSHNHL R3) | Phase II |
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
Immunotherapy
Stem cells transfused on day 0
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 verified protocol PubMed
Relapsed or refractory, further lines of therapy
Axicabtagene ciloleucel monotherapy
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Regimen
FDA-recommended dose |
Study | Evidence | Efficacy |
---|---|---|
Nellapu et al. 2017 (ZUMA-1) | Phase II, <20 pts in subgroup | 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 medications
- 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: 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 verified protocol PubMed
Pembrolizumab monotherapy
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Regimen
FDA-recommended dose |
Study | Evidence |
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Michot et al. 2016 (KEYNOTE-170) | Phase II (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
- 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. link to abstract