Primary mediastinal B-cell lymphoma

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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

ESMO

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

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

Regimen

Study	Evidence
Dunleavy et al. 2013	Phase II
Purroy et al. 2014	Pilot"|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 on days 1 to 4 (total dose per cycle: 200 mg/m²)
• Prednisone (Sterapred) 60 mg/m² PO BID on days 1 to 5
• Vincristine (Oncovin) 0.4 mg/m²/day IV continuous infusion over 96 hours on days 1 to 4 (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 on days 1 to 4 (total dose per cycle: 40 mg/m²)

Supportive medications

• Filgrastim (Neupogen) 300 mcg SQ 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 BID as needed for constipation
• Lactulose 20 g PO Q6H 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

1. 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
2. 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

Synonyms: R-CHOP-21, CHOP-R

Structured Concept: C9760 (NCI-T), C0393023 (NCI-MT/UMLS)

• Example orders for R-CHOP in lymphoma

Regimen

Study	Evidence	Comparator	Efficacy
Pfreundschuh et al. 2006 (MInT)	Phase III	CHOP CHOEP MACOP-B 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
• Radiation therapy: 30 to 40 Gy given to sites of primary bulky disease; 30 to 40 Gy to primary extranodal disease at physician discretion

Supportive medications

• Filgrastim (Neupogen) or Lenograstim (Granocyte) used at physician discretion for neutropenia

21-day cycle for 6 cycles

References

1. 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
   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
2. 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
   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

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	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 (Cytosar) 2000 mg/m² IV over 3 hours Q12H x 2 doses on day 2 (total of 2 doses)
• Cisplatin (Platinol) 100 mg/m² IV continuous infusion over 24 hours on day 1

21-day cycle for up to 3 cycles

References

1. 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	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

1. 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