Waldenström macroglobulinemia - historical

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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. Is there a regimen missing from this list? Please go to the main WM regimen page to find other regimens.

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


First-line therapy

Bortezomib & Rituximab (VR)

VR: Velcade (Bortezomib) & Rituximab

Regimen

Study Dates of enrollment Evidence
Ghobrial et al. 2010 (DFCI 06-008) 2006-2008 Phase 2

Targeted therapy

Supportive therapy

  • "Antiviral prophylaxis was recommended in all patients prior to initiation of therapy and for 3 months after completion of the six cycles."

28-day cycle for up to 6 cycles

References

  1. DFCI 06-008: Ghobrial IM, Hong F, Padmanabhan S, Badros A, Rourke M, Leduc R, Chuma S, Kunsman J, Warren D, Harris B, Sam A, Anderson KC, Richardson PG, Treon SP, Weller E, Matous J. Phase II trial of weekly bortezomib in combination with rituximab in relapsed or relapsed and refractory Waldenstrom macroglobulinemia. J Clin Oncol. 2010 Mar 10;28(8):1422-8. Epub 2010 Feb 8. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00422799
    1. Update: Ghobrial IM, Xie W, Padmanabhan S, Badros A, Rourke M, Leduc R, Chuma S, Kunsman J, Warren D, Poon T, Harris B, Sam A, Anderson KC, Richardson PG, Treon SP, Weller E, Matous J. Phase II trial of weekly bortezomib in combination with rituximab in untreated patients with Waldenström Macroglobulinemia. Am J Hematol. 2010 Sep;85(9):670-4. Epub 2010 Aug 25. link to original article dosing details in manuscript have been reviewed by our editors PubMed


Cladribine & Rituximab

Regimen

Study Dates of enrollment Evidence
Laszlo et al. 2010 2003-12 to 2007-02 Phase 2

Chemotherapy

Targeted therapy

1-month cycle for 4 cycles

References

  1. Laszlo D, Andreola G, Rigacci L, Fabbri A, Rabascio C, Mancuso P, Pruneri G, Radice D, Pinto A, Frigeri F, Calabrese L, Billio A, Bertolini F, Martinelli G. Rituximab and subcutaneous 2-chloro-2'-deoxyadenosine combination treatment for patients with Waldenstrom macroglobulinemia: clinical and biologic results of a phase II multicenter study. J Clin Oncol. 2010 May 1;28(13):2233-8. Epub 2010 Apr 5. link to original article dosing details in manuscript have been reviewed by our editors PubMed IEURONC_*II_204_003


FCR

FCR: Fludarabine, Cyclophosphamide, Rituximab

Regimen

Study Dates of enrollment Evidence
Tedeschi et al. 2011 2005-2008 Phase 2

Chemotherapy

Targeted therapy

Supportive therapy

28-day cycle for up to 6 cycles

References

  1. Tedeschi A, Benevolo G, Varettoni M, Battista ML, Zinzani PL, Visco C, Meneghini V, Pioltelli P, Sacchi S, Ricci F, Nichelatti M, Zaja F, Lazzarino M, Vitolo U, Morra E. Fludarabine plus cyclophosphamide and rituximab in Waldenstrom macroglobulinemia: an effective but myelosuppressive regimen to be offered to patients with advanced disease. Cancer. 2012 Jan 15;118(2):434-43. Epub 2011 Jul 5. link to original article dosing details in manuscript have been reviewed by our editors PubMed


Ofatumumab monotherapy

Regimen variant #1

Study Dates of enrollment Evidence
Furman et al. 2016 (GSK 110921) 2009-03-17 to 2011-02-24 Phase 2

Note: This study used two dosing schemas, based on a mid-study amendment. See paper for details about redosing based on response. It is not clear from the abstract how many patients were untreated versus relapsed. As of 10/15/2020, ofatumumab is no longer available for commercial purchase and is not being made available for this indication.

Targeted therapy

4-week course


Regimen variant #2

Study Dates of enrollment Evidence
Furman et al. 2016 (GSK 110921) 2009-03-17 to 2011-02-24 Phase 2

Note: This study used two dosing schemas, based on a mid-study amendment. See paper for details about redosing based on response. It is not clear from the abstract how many patients were untreated versus relapsed. As of 10/15/2020, ofatumumab is no longer available for commercial purchase and is not being made available for this indication.

Targeted therapy

5-week course

References

  1. GSK 110921: Furman RR, Eradat HA, DiRienzo CG, Hofmeister CC, Hayman SR, Leonard JP, Coleman M, Advani R, Chanan-Khan A, Switzky J, Liao QM, Shah D, Jewell RC, Lisby S, Lin TS. Once-weekly ofatumumab in untreated or relapsed Waldenström's macroglobulinaemia: an open-label, single-arm, phase 2 study. Lancet Haematol. 2017 Jan;4(1):e24-e34. Epub 2016 Nov 30. link to original article dosing details in abstract have been reviewed by our editors link to PMC article PubMed NCT00811733


R-CHOP

R-CHOP: Rituximab, Cyclophosphamide, Hydroxydaunorubicin, Oncovin, Prednisone
R-CHOP-21
CHOP-R

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Buske et al. 2009 2000-2003 Phase 3 (E-esc) CHOP Superior TTF

Targeted therapy

Chemotherapy

Glucocorticoid therapy

21-day cycle for 4 to 8 cycles

References

  1. Buske C, Hoster E, Dreyling M, Eimermacher H, Wandt H, Metzner B, Fuchs R, Bittenbring J, Woermann B, Hohloch K, Hess G, Ludwig WD, Schimke J, Schmitz S, Kneba M, Reiser M, Graeven U, Klapper W, Unterhalt M, Hiddemann W; German Low-Grade Lymphoma Study Group. The addition of rituximab to front-line therapy with CHOP (R-CHOP) results in a higher response rate and longer time to treatment failure in patients with lymphoplasmacytic lymphoma: results of a randomized trial of the German Low-Grade Lymphoma Study Group (GLSG). Leukemia. 2009 Jan;23(1):153-61. Epub 2008 Sep 25. link to original article dosing details in manuscript have been reviewed by our editors PubMed


Thalidomide & Rituximab

Regimen

Study Dates of enrollment Evidence
Treon et al. 2008 (DFCI 03-077) 2003 to not reported Phase 2

Targeted therapy

  • Thalidomide (Thalomid) as follows:
    • Cycle 1: 200 mg PO once per day on days 1 to 14, then 400 mg PO once per day on days 15 to 28
    • Cycles 2 to 13: 400 mg PO once per day on days 1 to 28
  • Rituximab (Rituxan) as follows:
    • Cycle 1: 375 mg/m2 IV once per day on days 8, 15, 22
    • Cycle 2: 375 mg/m2 IV once on day 1
    • Cycle 4: 375 mg/m2 IV once per day on days 1, 8, 15, 22

28-day cycle for 13 cycles (1 year)

References

  1. DFCI 03-077: Treon SP, Soumerai JD, Branagan AR, Hunter ZR, Patterson CJ, Ioakimidis L, Briccetti FM, Pasmantier M, Zimbler H, Cooper RB, Moore M, Hill J 2nd, Rauch A, Garbo L, Chu L, Chua C, Nantel SH, Lovett DR, Boedeker H, Sonneborn H, Howard J, Musto P, Ciccarelli BT, Hatjiharissi E, Anderson KC. Thalidomide and rituximab in Waldenstrom macroglobulinemia. Blood. 2008 Dec 1;112(12):4452-7. Epub 2008 Aug 19. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00142116


Thioguanine monotherapy

Regimen

Study Dates of enrollment Evidence
Weiss et al. 1963 1962 Pilot

Chemotherapy

Continued indefinitely

References

  1. Weiss CH, Demis DJ, Elgart ML, Brown CS, Crosby WH. Treatment of two cases of hyperglobulinemic purpura with thioguanine. N Engl J Med. 1963 Apr 4;268:753-6. link to original article dosing details in manuscript have been reviewed by our editors PubMed


Relapsed or refractory

Alemtuzumab monotherapy

Regimen

Study Dates of enrollment Evidence
Hale et al. 1988 1987-1988 Pilot
Treon et al. 2011 (DFCI 02-079) Not reported Phase 2

Note: Hale et al. 1998 is the first reported use of this monoclonal antibody and possibly the first clinical trial of monoclonal antibodies in cancer. One of the two patients had lymphoplasmacytoid lymphoma. Per DFCI 02-079, "Alemtuzumab is an active therapy.., but short- and long-term toxicities need to be carefully weighed against other available treatment options."

Targeted therapy

  • Alemtuzumab (Campath) as follows:
    • Cycle 1: 3 mg IV once on day 1, then 10 mg IV once on day 3, then 30 mg IV once on day 5
    • Cycles 2 to 13: 30 mg IV once per day on days 1, 3, 5

Supportive therapy

7-day cycle for 13 cycles

References

  1. Hale G, Dyer MJ, Clark MR, Phillips JM, Marcus R, Riechmann L, Winter G, Waldmann H. Remission induction in non-Hodgkin lymphoma with reshaped human monoclonal antibody CAMPATH-1H. Lancet. 1988 Dec 17;2(8625):1394-9. link to original article PubMed
  2. DFCI 02-079: Treon SP, Soumerai JD, Hunter ZR, Patterson CJ, Ioakimidis L, Kahl B, Boxer M. Long-term follow-up of symptomatic patients with lymphoplasmacytic lymphoma/Waldenström macroglobulinemia treated with the anti-CD52 monoclonal antibody alemtuzumab. Blood. 2011 Jul 14;118(2):276-81. Epub 2011 May 12. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00142181


Bortezomib monotherapy

Regimen variant #1, 4 cycles

Study Dates of enrollment Evidence
Dimopoulos et al. 2005 Not reported Phase 2, fewer than 20 pts

Targeted therapy

21-day cycle for 4 cycles


Regimen variant #2, 8 cycles

Study Dates of enrollment Evidence
Treon et al. 2007 (WMCTG 03-248) Not reported Phase 2

Targeted therapy

Up to 8 cycles (cycle duration not defined)


Regimen variant #3, response-adapted

Study Dates of enrollment Evidence
Chen et al. 2007 (NCIC-CTG I152) 2003-01 to 2005-03 Phase 2

Targeted therapy

21-day cycles until PD or 2 cycles past CR or stable PR

References

  1. Dimopoulos MA, Anagnostopoulos A, Kyrtsonis MC, Castritis E, Bitsaktsis A, Pangalis GA. Treatment of relapsed or refractory Waldenström's macroglobulinemia with bortezomib. Haematologica. 2005 Dec;90(12):1655-8. link to original article dosing details in abstract have been reviewed by our editors PubMed
  2. NCIC-CTG I152: Chen CI, Kouroukis CT, White D, Voralia M, Stadtmauer E, Stewart AK, Wright JJ, Powers J, Walsh W, Eisenhauer E; National Cancer Institute of Canada Clinical Trials Group. Bortezomib is active in patients with untreated or relapsed Waldenstrom's macroglobulinemia: a phase II study of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2007 Apr 20;25(12):1570-5. Epub 2007 Mar 12. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00045695
  3. WMCTG 03-248: Treon SP, Hunter ZR, Matous J, Joyce RM, Mannion B, Advani R, Cook D, Songer J, Hill J, Kaden BR, Sharon D, Steiss R, Leleu X, Branagan AR, Badros A. Multicenter clinical trial of bortezomib in relapsed/refractory Waldenstrom's macroglobulinemia: results of WMCTG Trial 03-248. Clin Cancer Res. 2007 Jun 1;13(11):3320-5. link to original article dosing details in manuscript have been reviewed by our editors PubMed


Bortezomib & Rituximab (VR)

VR: Velcade (Bortezomib) & Rituximab

Regimen

Study Dates of enrollment Evidence
Ghobrial et al. 2010 (DFCI 06-008) 2006-2008 Phase 2

Targeted therapy

Supportive therapy

  • "At the time of initiation of the study, the incidence of herpes zoster reactivation with bortezomib in WM was not well documented; therefore, antiviral prophylaxis was not mandated."

28-day cycle for up to 6 cycles

References

  1. DFCI 06-008: Ghobrial IM, Hong F, Padmanabhan S, Badros A, Rourke M, Leduc R, Chuma S, Kunsman J, Warren D, Harris B, Sam A, Anderson KC, Richardson PG, Treon SP, Weller E, Matous J. Phase II trial of weekly bortezomib in combination with rituximab in relapsed or relapsed and refractory Waldenstrom macroglobulinemia. J Clin Oncol. 2010 Mar 10;28(8):1422-8. Epub 2010 Feb 8. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00422799
    1. Update: Ghobrial IM, Xie W, Padmanabhan S, Badros A, Rourke M, Leduc R, Chuma S, Kunsman J, Warren D, Poon T, Harris B, Sam A, Anderson KC, Richardson PG, Treon SP, Weller E, Matous J. Phase II trial of weekly bortezomib in combination with rituximab in untreated patients with Waldenström Macroglobulinemia. Am J Hematol. 2010 Sep;85(9):670-4. Epub 2010 Aug 25. link to original article dosing details in manuscript have been reviewed by our editors PubMed


Cladribine & Rituximab

Regimen

Study Dates of enrollment Evidence
Laszlo et al. 2010 2003-12 to 2007-02 Phase 2

Chemotherapy

Targeted therapy

1-month cycle for 4 cycles

References

  1. Laszlo D, Andreola G, Rigacci L, Fabbri A, Rabascio C, Mancuso P, Pruneri G, Radice D, Pinto A, Frigeri F, Calabrese L, Billio A, Bertolini F, Martinelli G. Rituximab and subcutaneous 2-chloro-2'-deoxyadenosine combination treatment for patients with Waldenstrom macroglobulinemia: clinical and biologic results of a phase II multicenter study. J Clin Oncol. 2010 May 1;28(13):2233-8. Epub 2010 Apr 5. link to original article dosing details in manuscript have been reviewed by our editors PubMed IEURONC_*II_204_003


Ofatumumab monotherapy

Regimen variant #1

Study Dates of enrollment Evidence
Furman et al. 2016 (GSK 110921) 2009-03-17 to 2011-02-24 Phase 2

Note: This study used two dosing schemas, based on a mid-study amendment. See paper for details about redosing based on response. It is not clear from the abstract how many patients were untreated versus relapsed. As of 10/15/2020, ofatumumab is no longer available for commercial purchase and is not being made available for this indication.

Targeted therapy

4-week course


Regimen variant #2

Study Dates of enrollment Evidence
Furman et al. 2016 (GSK 110921) 2009-03-17 to 2011-02-24 Phase 2

Note: This study used two dosing schemas, based on a mid-study amendment. See paper for details about redosing based on response. It is not clear from the abstract how many patients were untreated versus relapsed. As of 10/15/2020, ofatumumab is no longer available for commercial purchase and is not being made available for this indication.

Targeted therapy

5-week course

References

  1. GSK 110921: Furman RR, Eradat HA, DiRienzo CG, Hofmeister CC, Hayman SR, Leonard JP, Coleman M, Advani R, Chanan-Khan A, Switzky J, Liao QM, Shah D, Jewell RC, Lisby S, Lin TS. Once-weekly ofatumumab in untreated or relapsed Waldenström's macroglobulinaemia: an open-label, single-arm, phase 2 study. Lancet Haematol. 2017 Jan;4(1):e24-e34. Epub 2016 Nov 30. link to original article dosing details in abstract have been reviewed by our editors link to PMC article PubMed NCT00811733


Panobinostat monotherapy

Regimen

Study Dates of enrollment Evidence
Ghobrial et al. 2013 (DFCI 09-071) 2009-07 to 2011-03 Phase 2

Targeted therapy

28-day cycles

References

  1. DFCI 09-071: Ghobrial IM, Campigotto F, Murphy TJ, Boswell EN, Banwait R, Azab F, Chuma S, Kunsman J, Donovan A, Masood F, Warren D, Rodig S, Anderson KC, Richardson PG, Weller E, Matous J. Results of a phase 2 trial of the single-agent histone deacetylase inhibitor panobinostat in patients with relapsed/refractory Waldenstrom macroglobulinemia. Blood. 2013 Feb 21;121(8):1296-303. Epub 2013 Jan 3. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00936611