Mediastinal gray-zone lymphoma

Carboplatin & Paclitaxel (CP)

CP: Carboplatin & Paclitaxel

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Forde et al. 2022 (CheckMate 816)	2017-2019	Phase 3 (C)	1a. CP & Nivolumab 1b. CVb & Nivolumab 1c. DC & Nivolumab	Inferior EFS

Note: there were additional comparator options depending on histology; see the respective histology-specific pages for more details. This study was conducted in the United States. The reason for the study was that an unanswered question at the time was whether adding an immune checkpoint inhibitor would improve outcomes.

Biomarker eligibility criteria

• CheckMate 816: No sensitizing EGFR or ALK mutations

Chemotherapy

• Carboplatin (Paraplatin) AUC 5 or 6 IV once on day 1
• Paclitaxel (Taxol) 175 or 200 mg/m² IV once on day 1

21-day cycle for 3 cycles

Subsequent treatment

• Complete resection

References

1. CheckMate 816: Forde PM, Spicer J, Lu S, Provencio M, Mitsudomi T, Awad MM, Felip E, Broderick SR, Brahmer JR, Swanson SJ, Kerr K, Wang C, Ciuleanu TE, Saylors GB, Tanaka F, Ito H, Chen KN, Liberman M, Vokes EE, Taube JM, Dorange C, Cai J, Fiore J, Jarkowski A, Balli D, Sausen M, Pandya D, Calvet CY, Girard N; CheckMate 816 Investigators. Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer. N Engl J Med. 2022 May 26;386(21):1973-1985. Epub 2022 Apr 11. link to original article contains dosing details in manuscript PubMed NCT02998528

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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

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

Synonyms: DA-EPOCH-R

Structured Concept: C63461 (NCI-T), C1882521 (NCI-MT/UMLS)

Regimen

Study	Evidence
Wilson et al. 2014	Phase II

Chemotherapy

• Rituximab (Rituxan) 375 mg/m² IV once per cycle or 1 day before the start of EPOCH (depending on reference)
• Etoposide (Vepesid) 50 mg/m²/day IV continuous infusion 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 on days 1 to 4 (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 on days 1 to 4 (total dose per cycle: 40 mg/m²)

Supportive medications

• Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting on day 6 and continuing until ANC greater than 5000/uL past nadir
• PCP prophylaxis with ONE of the following:
  • Trimethoprim/Sulfamethoxazole (Bactrim DS) 160/800 mg PO BID 3 days per week
    • Alternative used only in García-Suárez et al. 2007: cotrimoxazole 480 mg PO BID 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-adjustments

• Start cycle 1 as described above.
• Obtain CBCs twice per week for nadir measurements.
• If nadir ANC greater than 500/uL, increase etoposide, doxorubicin, and cyclophosphamide by 20% compared to previous cycle.
• If nadir ANC less than 500/uL on 1 or 2 measurements, use same doses as last cycle.
• If nadir ANC less than 500/uL 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/uL 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. 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 contains protocol link to PMC article PubMed

Relapsed or refractory

Brentuximab vedotin monotherapy

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Regimen

Study	Evidence
Bartlett et al. 2013	Phase II, <20 pts

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

Chemotherapy

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

21-day cycles, given until progression or unacceptable toxicity

References

1. Abstract: Nancy L. Bartlett, MD, Jeff P. Sharman, MD, Yasuhiro Oki, MD, Ranjana H. Advani, MD, Celeste M. Bello, MD, Jane N. Winter, MD, Yin Yang, MS, Dana A. Kennedy, PharmD and Eric D. Jacobsen, MD. A Phase 2 Study Of Brentuximab Vedotin In Patients With Relapsed Or Refractory CD30-Positive Non-Hodgkin Lymphomas: Interim Results In Patients With DLBCL and Other B-Cell Lymphomas. ASH Abstract 848. link to abstract