Difference between revisions of "Mediastinal gray-zone lymphoma"

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''Note: Mediastinal gray-zone lymphome (MGZL) is considered intermediate between [[Primary mediastinal B-cell lymphoma|primary mediastinal B-cell lymphoma (PMBL)]] and [[Classical Hodgkin lymphoma|nodular sclerosis Hodgkin lymphoma (NSHL)]]. Given that it is treated more similarly to the non-Hodgkin lymphoma, it is included here.''
−
''Note: Mediastinal gray-zone lymphome (MGZL) is considered intermediate between [[Primary mediastinal B-cell lymphoma|primary mediastinal B-cell lymphoma (PMBL)]] and [[Hodgkin lymphoma|nodular sclerosis Hodgkin lymphoma (NSHL)]]. Given that it is treated more similarly to the non-Hodgkin lymphoma, it is included here.''
 
−
 
 
 
=Untreated=
 
=Untreated=
−
 
 
==DA-R-EPOCH {{#subobject:856660|Regimen=1}}==
 
==DA-R-EPOCH {{#subobject:856660|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)
 
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)
 
<br>DA-EPOCH-R
 
<br>DA-EPOCH-R
 +
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen {{#subobject:3202d4|Variant=1}}===
 
===Regimen {{#subobject:3202d4|Variant=1}}===
−
{| class="wikitable" style="width: 40%; text-align:center;"  
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{| class="wikitable sortable" style="width: 60%; text-align:center;"  
−
!style="width: 25%"|Study
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!style="width: 33%"|Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
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!style="width: 33%"|Dates of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4155269/ Wilson et al. 2014 (NCI 93-C-0133<sub>MGZL</sub>)]
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4155269/ Wilson et al. 2014 (NCI 93-C-0133<sub>MGZL</sub>)]
 +
|NR
 
|style="background-color:#91cf61"|Phase 2
 
|style="background-color:#91cf61"|Phase 2
 
|-
 
|-
 
|}
 
|}
 
''Note: this should be considered a substudy under the master protocol NCI 93-C-0133.''
 
''Note: this should be considered a substudy under the master protocol NCI 93-C-0133.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Targeted therapy====
 
====Targeted therapy====
 
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per cycle or 1 day before the start of EPOCH (depending on reference)
 
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per cycle or 1 day before the start of EPOCH (depending on reference)
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*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV over 15 minutes once on day 5
 
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV over 15 minutes once on day 5
 
*[[Doxorubicin (Adriamycin)]] 10 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 40 mg/m<sup>2</sup>)
 
*[[Doxorubicin (Adriamycin)]] 10 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 40 mg/m<sup>2</sup>)
−
 
 
====Glucocorticoid therapy====
 
====Glucocorticoid therapy====
 
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> PO twice per day on days 1 to 5
 
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> PO twice per day on days 1 to 5
−
 
+
====Supportive therapy====
−
====Supportive medications====
+
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting on day 6 and continuing until ANC greater than 5000/μL past nadir
−
*[[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:
 
*PCP prophylaxis with ONE of the following:
 
**[[Trimethoprim-Sulfamethoxazole (Bactrim DS)]] 160/800 mg PO twice per day 3 days per week  
 
**[[Trimethoprim-Sulfamethoxazole (Bactrim DS)]] 160/800 mg PO twice per day 3 days per week  
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**[[Pentamidine (Nebupent)]] 300 mg nebulized every 28 days
 
**[[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.
 
*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'''
 
'''21-day cycle for 6 to 8 cycles'''
−
 
+
</div>
−
====Dose-adjustments====
+
<div class="toccolours" style="background-color:#fff2ae">
 +
====Dose and schedule modifications====
 
*Start cycle 1 as described above.
 
*Start cycle 1 as described above.
 
*Obtain CBCs twice per week for nadir measurements.
 
*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 greater than 500/μL, 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/μL 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.
+
*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 10<sup>9</sup>/L on at least 1 measurement, decrease etoposide, doxorubicin, and cyclophosphamide by 20% compared to previous cycle.
 
*And/or if nadir platelet count less than 25 x 10<sup>9</sup>/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.
 
*'''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 10<sup>9</sup>/L. If counts are below those levels, check daily CBC and continue growth factor support until counts are adequate and next cycle can start.
+
*Can start new cycle every 21 days if ANC greater than 1000/μL and platelets greater than 100 x 10<sup>9</sup>/L. If counts are below those levels, check daily CBC and continue growth factor support until counts are adequate and next cycle can start.
−
 
+
</div></div>
 
===References===
 
===References===
−
# '''NCI 93-C-0133:''' 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. [http://www.bloodjournal.org/content/124/10/1563.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4155269/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25024303 PubMed]
+
# '''NCI 93-C-0133<sub>MGZL</sub>:''' 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. [http://www.bloodjournal.org/content/124/10/1563.long link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4155269/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25024303/ PubMed]
−
 
 
 
=Relapsed or refractory=
 
=Relapsed or refractory=
−
 
 
==Brentuximab vedotin monotherapy {{#subobject:148648|Regimen=1}}==
 
==Brentuximab vedotin monotherapy {{#subobject:148648|Regimen=1}}==
−
 
+
<div class="toccolours" style="background-color:#eeeeee">
−
 
 
 
===Regimen {{#subobject:bb7dfb|Variant=1}}===
 
===Regimen {{#subobject:bb7dfb|Variant=1}}===
−
{| class="wikitable" style="width: 40%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
−
!style="width: 25%"|Study
+
!style="width: 33%"|Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 33%"|Dates of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[http://www.bloodjournal.org/content/125/9/1394 Jacobsen et al. 2015 (SGN35-012)]
+
|[http://www.bloodjournal.org/content/125/9/1394 Jacobsen et al. 2015 (SGN35-012<sub>CD30+B-NHL</sub>)]
−
|style="background-color:#ffffbe"|Phase 2, <20 pts in this subgroup
+
|2011-08 to 2013-08
 +
|style="background-color:#ffffbe"|Phase 2, fewer than 20 pts in this subgroup
 
|-
 
|-
 
|}
 
|}
−
''This regimen was evaluated in patients with CD30+ non-Hodgkin lymphoma, as determined by immunohistochemistry.''
+
''Note: This regimen was evaluated in patients with CD30+ non-Hodgkin lymphoma, as determined by immunohistochemistry.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Antibody-drug conjugate therapy====
 
====Antibody-drug conjugate therapy====
 
*[[Brentuximab vedotin (Adcetris)]] 1.8 mg/kg IV over 30 minutes once on day 1
 
*[[Brentuximab vedotin (Adcetris)]] 1.8 mg/kg IV over 30 minutes once on day 1
−
 
 
'''21-day cycles'''
 
'''21-day cycles'''
−
 
+
</div></div>
 
===References===
 
===References===
 
<!-- '''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. [https://ash.confex.com/ash/2013/webprogram/Paper59695.html link to abstract] -->
 
<!-- '''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. [https://ash.confex.com/ash/2013/webprogram/Paper59695.html link to abstract] -->
−
# '''SGN35-012:''' 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. [http://www.bloodjournal.org/content/125/9/1394 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/25573987 PubMed] NCT01421667
+
# '''SGN35-012<sub>CD30+B-NHL</sub>:''' 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. [http://www.bloodjournal.org/content/125/9/1394 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25573987/ PubMed] [https://clinicaltrials.gov/study/NCT01421667 NCT01421667]
−
 
 
 
[[Category:Mediastinal gray-zone lymphoma regimens]]
 
[[Category:Mediastinal gray-zone lymphoma regimens]]
 
[[Category:Disease-specific pages]]
 
[[Category:Disease-specific pages]]
−
[[Category:Aggressive lymphomas]]
+
[[Category:Aggressive non-Hodgkin lymphomas]]
−
[[Category:Non-Hodgkin lymphomas]]
+
[[Category:B-cell lymphomas]]

Latest revision as of 12:26, 1 March 2024

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Section editor
TarsheenSethi.jpg
 Tarsheen Sethi, MD, MSCI
Yale University
New Haven, CT, USA
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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) NR 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

Glucocorticoid therapy

Supportive therapy

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-0133MGZL: 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 dosing details in abstract 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

21-day cycles

References

  1. SGN35-012CD30+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 contains dosing details in manuscript PubMed NCT01421667
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