Hodgkin lymphoma, nodular lymphocyte-predominant

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9 regimens on this page 11 variants on this page

Untreated

ABVD

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ABVD: Adriamycin (Doxorubicin), Bleomycin, Vinblastine, Dacarbazine

Regimen

Study	Evidence
Savage et al. 2011	Retrospective
Xing et al. 2014	Retrospective

Chemotherapy

• Doxorubicin (Adriamycin) 25 mg/m² IV once per day on days 1 & 15
• Bleomycin (Blenoxane) 10 units/m² IV once per day on days 1 & 15 (1 unit test dose with cycle 1 doses, 60 minutes prior to remainder of full dose)
• Vinblastine (Velban) 6 mg/m² IV once per day on days 1 & 15
• Dacarbazine (DTIC) 375 mg/m² IV once per day on days 1 & 15
• +/- Rituximab (Rituxan); schedule & number of cycles is not well-established. One potential option is 375 mg/m² IV weekly x 4 weeks on cycle 1 (see single agent rituximab). Use in subsequent cycles is not well-documented.

28-day cycle for 2 to 6 cycles based on stage, response, and whether radiation therapy is used.

References

1. Retrospective: Savage KJ, Skinnider B, Al-Mansour M, Sehn LH, Gascoyne RD, Connors JM. Treating limited-stage nodular lymphocyte predominant Hodgkin lymphoma similarly to classical Hodgkin lymphoma with ABVD may improve outcome. Blood. 2011 Oct 27;118(17):4585-90. link to original article PubMed
2. Retrospective: Xing KH, Connors JM, Lai A, Al-Mansour M, Sehn LH, Villa D, Klasa R, Shenkier T, Gascoyne RD, Skinnider B, Savage KJ. Advanced-stage nodular lymphocyte predominant Hodgkin lymphoma compared with classical Hodgkin lymphoma: a matched pair outcome analysis. Blood. 2014 Jun 5;123(23):3567-73. Epub 2014 Apr 8. link to original article PubMed

CHOP

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CHOP: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone

Regimen

The below regimen was intended for DLBCL; no primary reference is to our knowledge available for use of CHOP in NLP-HL.

Chemotherapy

• 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 2mg per cycle) IV once on day 1
• Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5

21-day cycle for 6 to 8 cycles (number of cycles for CHOP in NLPHL is not well-established)

References

1. Feugier P, Van Hoof A, Sebban C, Solal-Celigny P, Bouabdallah R, Fermé C, Christian B, Lepage E, Tilly H, Morschhauser F, Gaulard P, Salles G, Bosly A, Gisselbrecht C, Reyes F, Coiffier B. Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol. 2005 Jun 20;23(18):4117-26. link to original article contains protocol PubMed

CVP

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CVP: Cyclophosphamide, Vincristine, Prednisone

Regimen

The below regimen was intended for follicular lymphoma; no primary reference is to our knowledge available for use of CVP in NLP-HL.

Chemotherapy

• Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
• Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2mg per cycle) IV once on day 1
• Prednisone (Sterapred) 40 mg/m² PO once per day on days 1 to 5

21-day cycle for up to 8 cycles (number of cycles for CVP in NLPHL is not well-established)

References

1. Marcus R, Imrie K, Belch A, Cunningham D, Flores E, Catalano J, Solal-Celigny P, Offner F, Walewski J, Raposo J, Jack A, Smith P. CVP chemotherapy plus rituximab compared with CVP as first-line treatment for advanced follicular lymphoma. Blood. 2005 Feb 15;105(4):1417-23. link to original article contains protocol PubMed

EPOCH

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EPOCH: Etoposide, Prednisone, Oncovin (Vincristine), Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin)

Regimen #1, Wilson et al. 1993 - original EPOCH protocol

Chemotherapy

• Etoposide (Vepesid) 50 mg/m2/day (200 mg/m² total) IV continuous infusion on days 1 to 4
• Prednisone (Sterapred) 60 mg/m2/day PO on days 1 to 5 (regimen originally was days 1 to 6, but now is just days 1 to 5)
• Vincristine (Oncovin) 0.4 mg/m2/day (1.6 mg/m² total) (sometimes capped at maximum total dose of 2mg per cycle) IV continuous infusion on days 1 to 4
• Doxorubicin (Adriamycin) 10 mg/m2/day (40 mg/m² total) IV continuous infusion on days 1 to 4
• Cyclophosphamide (Cytoxan) 750 mg/m² IV over 15 minutes on day 5 (regimen originally was day 6, but now is day 5)

Supportive medications

• PCP prophylaxis (choose one)
  • Trimethoprim/Sulfamethoxazole (Bactrim DS) (160/800 mg) PO BID 3 days per week
  • Atovaquone (Mepron) 1500 mg PO daily
  • Pentamidine (Nebupent) 300 mg nebulized Q28days
• Filgrastim (Neupogen) 5 mcg/kg SQ daily start day 6 and continue until ANC >5,000/uL past nadir

21-day cycle for 6 to 8 cycles

Regimen #2, Wilson et al. 2002 - dose-adjusted EPOCH

Chemotherapy

• Etoposide (Vepesid) 50 mg/m2/day (200 mg/m² total) IV continuous infusion on days 1 to 4
• Prednisone (Sterapred) 60 mg/m² PO BID on days 1 to 5
• Vincristine (Oncovin) 0.4 mg/m2/day (1.6 mg/m² total) (not capped in the paper, but sometimes capped at a maximum total dose of 2mg per cycle) IV continuous infusion on days 1 to 4
• Doxorubicin (Adriamycin) 10 mg/m2/day (40 mg/m² total) IV continuous infusion on days 1 to 4
• Cyclophosphamide (Cytoxan) 750 mg/m² IV over 15 minutes on day 5

Supportive medications

• PCP prophylaxis (choose one)
  • Trimethoprim/Sulfamethoxazole (Bactrim DS) (160/800 mg) PO BID 3 days per week
  • Atovaquone (Mepron) 1500 mg PO daily
  • Pentamidine (Nebupent) 300 mg nebulized Q28days
• Filgrastim (Neupogen) 5 mcg/kg SQ daily start day 6 and continue until ANC >5,000/uL past nadir

21-day cycle for 6 to 8 cycles

Dose-adjustments for EPOCH protocol:

• Start cycle 1 as described above
• Obtain twice per week CBCs for nadir measurements
• If nadir ANC >500, increase Etoposide (Vepesid), Doxorubicin (Adriamycin), and Cyclophosphamide (Cytoxan) by 20% compared to previous cycle.
• If nadir ANC <500 on 1 or 2 measurements, use same doses as last cycle
• If nadir ANC <500 on at least 3 measurements, decrease Etoposide (Vepesid), Doxorubicin (Adriamycin), and Cyclophosphamide (Cytoxan) by 20% compared to previous cycle.
• And/or if nadir platelet count <25 on at least 1 measurement, decrease Etoposide (Vepesid), Doxorubicin (Adriamycin), and Cyclophosphamide (Cytoxan) 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 Q21days if ANC >1,000 and platelets >100. If counts are below those levels, check daily CBC and continue growth factor support until counts are adequate and next cycle can start.

Historic dose adjustments for hematologic toxicity: These adjustments were in the original paper for standard EPOCH, which are much less relevant due to growth factor support.
If ANC on day 1 is:

• >1,500, full dose cyclophosphamide
• 1,000-1,500, reduce cyclophosphamide by 187 mg/m² (equal to 25% dose reduction)
• <1,000, hold EPOCH
• If ANC nadir is <500, reduce cyclophosphamide an additional 187 mg/m2
• If ANC nadir is >500 and patient had previously been dose-reduced, increase cyclophosphamide dose by 187 mg/m2

References

1. Wilson WH, Bryant G, Bates S, Fojo A, Wittes RE, Steinberg SM, Kohler DR, Jaffe ES, Herdt J, Cheson BD et al. EPOCH chemotherapy: toxicity and efficacy in relapsed and refractory non-Hodgkin's lymphoma. J Clin Oncol. 1993 Aug;11(8):1573-82 link to original article contains protocol PubMed
2. Wilson WH, Grossbard ML, Pittaluga S, Cole D, Pearson D, Drbohlav N, Steinberg SM, Little RF, Janik J, Gutierrez M, Raffeld M, Staudt L, Cheson BD, Longo DL, Harris N, Jaffe ES, Chabner BA, Wittes R, Balis F. Dose-adjusted EPOCH chemotherapy for untreated large B-cell lymphomas: a pharmacodynamic approach with high efficacy. Blood. 2002 Apr 15;99(8):2685-93. link to original article contains protocol PubMed content property of HemOnc.org
3. Wilson WH, Dunleavy K, Pittaluga S, Hegde U, Grant N, Steinberg SM, Raffeld M, Gutierrez M, Chabner BA, Staudt L, Jaffe ES, Janik JE. Phase II study of dose-adjusted EPOCH and rituximab in untreated diffuse large B-cell lymphoma with analysis of germinal center and post-germinal center biomarkers. J Clin Oncol. 2008 Jun 1;26(16):2717-24. link to original article PubMed

R-CHOP

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R-CHOP: Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone

Regimen

Study	Evidence
Fanale et al. 2010	Retrospective

The below regimen was intended for DLBCL; no prospective reference is to our knowledge available for use of R-CHOP in NLP-HL.

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 2mg per cycle) IV once on day 1
• Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5

21-day cycle for 6 to 8 cycles

References

1. Retrospective Abstract: Fanale, Michelle A., Lai, Chao-Ming, McLaughlin, Peter, Romaguera, Jorge, Fayad, Luis, Hagemeister, Fredrick, Samaniego, Felipe, Rodriguez, Maria Alma, Neelapu, Sattva S., Shah, Jatin J, Kwak, Larry, Dong, Wenli, Reed, Valerie, Dabaja, Bouthaina S., Popat, Uday, Younes, Anas. Outcomes of Nodular Lymphocyte Predominant Hodgkin's Lymphoma (NLPHL) Patients Treated with R-CHOP. ASH Annual Meeting Abstracts 2010 116: 2812 link to abstract

R-CVP

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R-CVP: Rituximab, Cyclophosphamide, Vincristine, Prednisone

Regimen

Chemotherapy

• Rituximab (Rituxan) 375 mg/m² IV once on day 1
• Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
• Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2mg per cycle) IV once on day 1
• Prednisone (Sterapred) 40 mg/m² PO once daily on days 1 to 5

21-day cycle for up to 8 cycles (number of cycles for R-CVP in NLPHL is not well-established)

References

See references for CVP

R-EPOCH

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

Regimen #1, Wilson et al. 1993 - original EPOCH protocol (which did not include rituximab)

Chemotherapy

• Rituximab (Rituxan) 375 mg/m² IV once per cycle (usually given as outpatient due to reimbursement issues)
• Etoposide (Vepesid) 50 mg/m2/day (200 mg/m² total) IV continuous infusion on days 1 to 4
• Prednisone (Sterapred) 60 mg/m2/day PO on days 1 to 5 (regimen originally was days 1 to 6, but now is just days 1 to 5)
• Vincristine (Oncovin) 0.4 mg/m2/day (1.6 mg/m² total) (sometimes capped at maximum total dose of 2mg per cycle) IV continuous infusion on days 1 to 4
• Doxorubicin (Adriamycin) 10 mg/m2/day (40 mg/m² total) IV continuous infusion on days 1 to 4
• Cyclophosphamide (Cytoxan) 750 mg/m² IV over 15 minutes on day 5 (regimen originally was day 6, but now is day 5)

Supportive medications

• PCP prophylaxis (choose one)
  • Trimethoprim/Sulfamethoxazole (Bactrim DS) (160/800 mg) PO BID 3 days per week
  • Atovaquone (Mepron) 1500 mg PO daily
  • Pentamidine (Nebupent) 300 mg nebulized Q28days
• Filgrastim (Neupogen) 5 mcg/kg SQ daily start day 6 and continue until ANC >5,000/uL past nadir

21-day cycle for 6 to 8 cycles

Regimen #2, Wilson et al. 2002 - dose-adjusted EPOCH

Chemotherapy

• Rituximab (Rituxan) 375 mg/m² IV once per cycle (usually given as outpatient due to reimbursement issues)
• Etoposide (Vepesid) 50 mg/m2/day (200 mg/m² total) IV continuous infusion on days 1 to 4
• Prednisone (Sterapred) 60 mg/m² PO BID on days 1 to 5
• Vincristine (Oncovin) 0.4 mg/m2/day (1.6 mg/m² total) (not capped in the paper, but sometimes capped at a maximum total dose of 2mg per cycle) IV continuous infusion on days 1 to 4
• Doxorubicin (Adriamycin) 10 mg/m2/day (40 mg/m² total) IV continuous infusion on days 1 to 4
• Cyclophosphamide (Cytoxan) 750 mg/m² IV over 15 minutes on day 5

Supportive medications

• PCP prophylaxis (choose one)
  • Trimethoprim/Sulfamethoxazole (Bactrim DS) (160/800 mg) PO BID 3 days per week
  • Atovaquone (Mepron) 1500 mg PO daily
  • Pentamidine (Nebupent) 300 mg nebulized Q28days
• Filgrastim (Neupogen) 5 mcg/kg SQ daily start day 6 and continue until ANC >5,000/uL past nadir

21-day cycle for 6 to 8 cycles

Dose-adjusted R-EPOCH protocol

• Start cycle 1 as described above
• Obtain twice per week CBCs for nadir measurements
• If nadir ANC >500, increase etoposide, doxorubicin, and cyclophosphamide by 20% compared to previous cycle.
• If nadir ANC <500 on 1 or 2 measurements, use same doses as last cycle
• If nadir ANC <500 on at least 3 measurements, decrease etoposide, doxorubicin, and cyclophosphamide by 20% compared to previous cycle.
• And/or if nadir platelet count <25 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 Q21days if ANC >1,000 and platelets >100. If counts are below those levels, check daily CBC and continue growth factor support until counts are adequate and next cycle can start.

Historic dose adjustments for hematologic toxicity

These adjustments were in the original paper for standard EPOCH, which are much less relevant due to growth factor support.
If ANC on day 1 is:

• >1,500, full dose cyclophosphamide
• 1,000-1,500, reduce cyclophosphamide by 187 mg/m² (equal to 25% dose reduction)
• <1,000, hold EPOCH
• If ANC nadir is <500, reduce cyclophosphamide an additional 187 mg/m2
• If ANC nadir is >500 and patient had previously been dose-reduced, increase cyclophosphamide dose by 187 mg/m2

References

See references for EPOCH

Rituximab (Rituxan)

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Regimen #1 (4-week course)

Study	Evidence
Rehwald et al. 2003	Phase II
Ekstrand et al. 2003	Phase II
Advani et al. 2014	Phase II

Chemotherapy

• Rituximab (Rituxan) 375 mg/m² IV once per week x 4 weeks

Supportive medications

• Acetaminophen (Tylenol) 650 mg PO 30 minutes prior to each dose
• Diphenhydramine (Benadryl) 25 mg PO 30 minutes prior to each dose

One course of 4 week therapy

Regimen #2, with maintenance

Study	Evidence
Advani et al. 2014	Phase II, <20 patients in this arm

Chemotherapy

• Rituximab (Rituxan) 375 mg/m² IV once per week x 4 weeks

One course, followed by maintenance:

• Rituximab (Rituxan) 375 mg/m² IV once per week x 4 weeks

One course every 6 month for 2 years

References

1. Rehwald U, Schulz H, Reiser M, Sieber M, Staak JO, Morschhauser F, Driessen C, Rudiger T, Muller-Hermelink K, Diehl V, Engert A; German Hodgkin Lymphoma Study Group (GHSG). Treatment of relapsed CD20+ Hodgkin lymphoma with the monoclonal antibody rituximab is effective and well tolerated: results of a phase 2 trial of the German Hodgkin Lymphoma Study Group. Blood. 2003 Jan 15;101(2):420-4. link to original article contains verified protocol PubMed
   1. Update: Schulz H, Rehwald U, Morschhauser F, Elter T, Driessen C, Rüdiger T, Borchmann P, Schnell R, Diehl V, Engert A, Reiser M. Rituximab in relapsed lymphocyte-predominant Hodgkin lymphoma: long-term results of a phase 2 trial by the German Hodgkin Lymphoma Study Group (GHSG). Blood. 2008 Jan 1;111(1):109-11. link to original article contains protocol PubMed
2. Ekstrand BC, Lucas JB, Horwitz SM, Fan Z, Breslin S, Hoppe RT, Natkunam Y, Bartlett NL, Horning SJ. Rituximab in lymphocyte-predominant Hodgkin disease: results of a phase 2 trial. Blood. 2003 Jun 1;101(11):4285-9. link to original article contains protocol PubMed
3. Advani RH, Horning SJ, Hoppe RT, Daadi S, Allen J, Natkunam Y, Bartlett NL. Mature Results of a Phase II Study of Rituximab Therapy for Nodular Lymphocyte-Predominant Hodgkin Lymphoma. J Clin Oncol. 2014 Mar 20;32(9):912-8. Epub 2014 Feb 10. link to original article contains verified protocol PubMed