Mediastinal gray-zone lymphoma

Section editor
	Tarsheen Sethi, MD, MSCI Yale University New Haven, CT, USA LinkedIn

Last updated on 2024-07-23: 2 regimens on this page 2 variants on this page

Note: Mediastinal gray-zone lymphome (MGZL) is considered intermediate between primary mediastinal B-cell lymphoma (PMBL) and nodular sclerosis Hodgkin lymphoma (NSHL). Given that it is treated more similarly to the non-Hodgkin lymphoma, it is included here.

Untreated

DA-R-EPOCH

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

Regimen

Study	Dates of enrollment	Evidence
Wilson et al. 2014 (NCI 93-C-0133MGZL)	Not reported	Phase 2

Note: this should be considered a substudy under the master protocol NCI 93-C-0133.

Targeted therapy

• Rituximab (Rituxan) 375 mg/m² IV once per cycle or 1 day before the start of EPOCH (depending on reference)

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 15 minutes 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) 5 mcg/kg SC once per day, starting on day 6 and continuing until ANC greater than 5000/μL past nadir
• PCP prophylaxis with ONE of the following:
  • Trimethoprim-Sulfamethoxazole (Bactrim DS) 160/800 mg PO twice per day 3 days per week
    • Alternative used only in García-Suárez et al. 2007: cotrimoxazole 480 mg PO twice per day 3 days per week
  • Atovaquone (Mepron) 1500 mg PO once per day
  • Pentamidine (Nebupent) 300 mg nebulized every 28 days
• Only in García-Suárez et al. 2007: Darbepoetin alfa (Aranesp) 2.25 mcg/kg SC when hemoglobin concentration was less than or equal to 10 g/dL.

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 20% compared to previous cycle.
• If nadir ANC less than 500/μL on 1 or 2 measurements, use same doses as last cycle.
• If nadir ANC less than 500/μL on at least 3 measurements, decrease etoposide, doxorubicin, and cyclophosphamide by 20% compared to previous cycle.
• And/or if nadir platelet count less than 25 x 10⁹/L on at least 1 measurement, decrease etoposide, doxorubicin, and cyclophosphamide by 20% compared to previous cycle.
• Dose adjustments below the cycle 1 starting dose only applies to cyclophosphamide. The lowest etoposide and doxorubicin would be dosed at is the original cycle 1 dose.
• Can start new cycle every 21 days if ANC greater than 1000/μL and platelets greater than 100 x 10⁹/L. If counts are below those levels, check daily CBC and continue growth factor support until counts are adequate and next cycle can start.

References

1. NCI 93-C-0133_MGZL: Wilson WH, Pittaluga S, Nicolae A, Camphausen K, Shovlin M, Steinberg SM, Roschewski M, Staudt LM, Jaffe ES, Dunleavy K. A prospective study of mediastinal gray-zone lymphoma. Blood. 2014 Sep 4;124(10):1563-9. Epub 2014 Jul 14. link to original article dosing details in abstract have been reviewed by our editors link to PMC article PubMed

Relapsed or refractory

Brentuximab vedotin monotherapy

Regimen

Study	Dates of enrollment	Evidence
Jacobsen et al. 2015 (SGN35-012CD30+B-NHL)	2011-08 to 2013-08	Phase 2, fewer than 20 pts in this subgroup

Note: This regimen was evaluated in patients with CD30+ non-Hodgkin lymphoma, as determined by immunohistochemistry.

Antibody-drug conjugate therapy

• Brentuximab vedotin (Adcetris) 1.8 mg/kg IV over 30 minutes once on day 1

21-day cycles

References

1. SGN35-012_CD30+B-NHL: Jacobsen ED, Sharman JP, Oki Y, Advani RH, Winter JN, Bello CM, Spitzer G, Palanca-Wessels MC, Kennedy DA, Levine P, Yang J, Bartlett NL. Brentuximab vedotin demonstrates objective responses in a phase 2 study of relapsed/refractory DLBCL with variable CD30 expression. Blood. 2015 Feb 26;125(9):1394-402. Epub 2015 Jan 8. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01421667