Hodgkin lymphoma, nodular lymphocyte-predominant

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 Sanjai Sharma, MD
Sequoia Regional Cancer Center
Visalia, CA, USA
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This page contains histology-specific studies. For the more general classical Hodgkin lymphoma page, follow this link.

  • We have moved How I Treat articles to a dedicated page.
9 regimens on this page
11 variants on this page


Guidelines

Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.

JCO "Oncology Grand Rounds"

NCCN

Untreated

ABVD

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

Regimen

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

Note: there are some reports of using rituximab although schedule & number of cycles is not well-established.

Chemotherapy

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. Epub 2011 Aug 26. 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

CHOP: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Predniso(lo)ne

Regimen

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

Chemotherapy

Glucocorticoid therapy

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; Groupe d'Etude des Lymphomes de l'Adulte. 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 dosing details in abstract PubMed

CVP (Vinblastine/Prednisolone)

CVP: Cyclophosphamide, Vinblastine, Prednisolone

Regimen

Study Evidence
Shankar et al. 2011 Retrospective

Note: contrary to most CVP regimens, this one uses vinblastine, not vincristine. This regimen was used in adolescents with early stage disease; note that there is a discrepancy between the abstract and the body of the manuscript regarding number of days that prednisolone is taken for.

Chemotherapy

Glucocorticoid therapy

14- to 21-day cycle for 3 cycles

References

  1. Retrospective: Shankar A, Hall GW, Gorde-Grosjean S, Hasenclever D, Leblanc T, Hayward J, Lambilliotte A, Daw S, Perel Y, McCarthy K, Lejars O, Coulomb A, Oberlin WO, Wallace WH, Landman-Parker J. Treatment outcome after low intensity chemotherapy [CVP] in children and adolescents with early stage nodular lymphocyte predominant Hodgkin's lymphoma - an Anglo-French collaborative report. Eur J Cancer. 2012 Jul;48(11):1700-6. Epub 2011 Nov 15. link to original article contains dosing details in manuscript PubMed

EPOCH

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

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

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, sometimes capped at maximum total dose of 2 mg per cycle)
  • Doxorubicin (Adriamycin) 10 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 40 mg/m2)
  • Cyclophosphamide (Cytoxan) 750 mg/m2 IV over 15 minutes once on day 5 (regimen originally was day 6, but now is day 5)

Glucocorticoid therapy

  • 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)

Supportive therapy

21-day cycle for 6 to 8 cycles


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

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, sometimes capped at maximum total dose of 2 mg per cycle)
  • Doxorubicin (Adriamycin) 10 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 40 mg/m2)
  • Cyclophosphamide (Cytoxan) 750 mg/m2 IV over 15 minutes once on day 5

Glucocorticoid therapy

Supportive therapy

21-day cycle for 6 to 8 cycles

Dose and schedule modifications

  • Start cycle 1 as described above
  • Obtain twice per week CBCs for nadir measurements
  • If nadir ANC greater than 500/μL, increase Etoposide (Vepesid), Doxorubicin (Adriamycin), and Cyclophosphamide (Cytoxan) 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 (Vepesid), Doxorubicin (Adriamycin), and Cyclophosphamide (Cytoxan) 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 (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 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.

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:

  • greater than 1500/μL, full dose cyclophosphamide
  • 1000 to 1500/μL, reduce cyclophosphamide by 187 mg/m2 (equal to 25% dose reduction)
  • less than 1000/μL, hold EPOCH
  • If ANC nadir is less than 500/μL, reduce cyclophosphamide an additional 187 mg/m2
  • If ANC nadir is greater than 500/μL 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 dosing details in abstract 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 dosing details in abstract 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 link to PMC article PubMed

R-CHOP

R-CHOP: Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Predniso(lo)ne

Regimen

Study Evidence
Fanale et al. 2017 Retrospective

The below regimen was intended for DLBCL; to our knowledge there are no prospective trials of R-CHOP in NLP-HL.

Targeted therapy

Chemotherapy

Glucocorticoid therapy

21-day cycle for 6 to 8 cycles

References

  1. Retrospective: Fanale MA, Cheah CY, Rich A, Medeiros LJ, Lai CM, Oki Y, Romaguera JE, Fayad LE, Hagemeister FB, Samaniego F, Rodriguez MA, Neelapu SS, Lee HJ, Nastoupil L, Fowler NH, Turturro F, Westin JR, Wang ML, McLaughlin P, Pinnix CC, Milgrom SA, Dabaja B, Horowitz SB, Younes A. Encouraging activity for R-CHOP in advanced stage nodular lymphocyte-predominant Hodgkin lymphoma. Blood. 2017 Jul 27;130(4):472-477. Epub 2017 May 18. link to original article link to PMC article PubMed

R-CVP

R-CVP: Rituximab, Cyclophosphamide, Vincristine, Prednisone

Regimen

Targeted therapy

Chemotherapy

Glucocorticoid therapy

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

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

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

Targeted therapy

  • Rituximab (Rituxan) 375 mg/m2 IV once per cycle (usually given as outpatient due to reimbursement issues)

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, sometimes capped at maximum total dose of 2 mg per cycle)
  • Doxorubicin (Adriamycin) 10 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 40 mg/m2)
  • Cyclophosphamide (Cytoxan) 750 mg/m2 IV over 15 minutes once on day 5 (regimen originally was day 6, but now is day 5)

Glucocorticoid therapy

  • 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)

Supportive therapy

21-day cycle for 6 to 8 cycles


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

Targeted therapy

  • Rituximab (Rituxan) 375 mg/m2 IV once per cycle (usually given as outpatient due to reimbursement issues)

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, sometimes capped at maximum total dose of 2 mg per cycle)
  • 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

Supportive therapy

21-day cycle for 6 to 8 cycles

Dose and schedule modifications

  • Start cycle 1 as described above
  • Obtain twice per week CBCs 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 Q21days 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.

Dose modifications, 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:

  • Greater than 1500/μL, full dose cyclophosphamide
  • 1000 to 1500/μL, reduce cyclophosphamide by 187 mg/m2 (equal to 25% dose reduction)
  • less than 1000/μL, hold EPOCH
  • If ANC nadir is less than 500/μL, reduce cyclophosphamide an additional 187 mg/m2
  • If ANC nadir is greater than 500/μL and patient had previously been dose-reduced, increase cyclophosphamide dose by 187 mg/m2

References

See references for EPOCH

Rituximab monotherapy

Regimen

Study Dates of enrollment Evidence
Rehwald et al. 2003 1999-2002 Phase 2
Ekstrand et al. 2003 1999-2002 Phase 2
Advani et al. 2014 (U2082N) 1999-2006 Phase 2
Eichenauer et al. 2011 (GHSG RIPL) 2006-2007 Phase 2

Targeted therapy

Supportive therapy

4-week course

Subsequent treatment

  • U2082N, after protocol amendment: Rituximab maintenance

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 dosing details in manuscript 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. Epub 2007 Oct 15. link to original article contains dosing details in abstract 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. Epub 2003 Feb 13. link to original article contains dosing details in abstract PubMed
  3. GHSG RIPL: Eichenauer DA, Fuchs M, Pluetschow A, Klimm B, Halbsguth T, Böll B, von Tresckow B, Nogová L, Borchmann P, Engert A. Phase 2 study of rituximab in newly diagnosed stage IA nodular lymphocyte-predominant Hodgkin lymphoma: a report from the German Hodgkin Study Group. Blood. 2011 Oct 20;118(16):4363-5. Epub 2011 Aug 9. link to original article contains dosing details in abstract PubMed NCT00346684
  4. U2082N: 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 dosing details in manuscript PubMed NCT00003820

Maintenance after upfront therapy

Rituximab monotherapy

Regimen

Study Dates of enrollment Evidence
Advani et al. 2014 (U2082N) 1999-2006 Phase 2, fewer than 20 patients in this arm

Preceding treatment

Targeted therapy

6-month cycle for 4 cycles (2 years)

References

  1. U2082N: 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 dosing details in manuscript PubMed NCT00003820
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