Waldenström macroglobulinemia - historical

Back to Top
The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only.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 2024-12-02:13 regimens on this page
17 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====
*Bortezomib (Velcade) 1.6 mg/m2 IV once per day on days 1, 8, 15
*Rituximab (Rituxan) as follows:
**Cycles 1 & 4: 375 mg/m2 IV once per day on days 1, 8, 15, 22
====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===
# 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 EuroPMC NCT00422799
## 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 EuroPMC
==Cladribine & Rituximab==
===Regimen===
Study 	Dates of enrollment	Evidence
Laszlo et al. 2010	2003-12 to 2007-02 	Phase 2
====Chemotherapy====
*Cladribine (Leustatin) 0.1 mg/kg SC once per day on days 1 to 5
====Targeted therapy====
*Rituximab (Rituxan) 375 mg/m2 IV once on day 1
1-month cycle for 4 cycles
===References===
# 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 EuroPMC IEURONC_*II_204_003
==FCR==
FCR: Fludarabine, Cyclophosphamide, Rituximab
===Regimen===
Study 	Dates of enrollment	Evidence
Tedeschi et al. 2011	2005-2008 	Phase 2
====Chemotherapy====
*Fludarabine (Fludara) 25 mg/m2 IV once per day on days 2 to 4
*Cyclophosphamide (Cytoxan) 250 mg/m2 IV once per day on days 2 to 4
====Targeted therapy====
*Rituximab (Rituxan) 375 mg/m2 IV once on day 1
====Supportive therapy====
*Diphenhydramine (Benadryl) (dose not specified) IV once on day 1, prior to rituximab 
*Acetaminophen (Tylenol) (dose not specified) PO once on day 1, prior to rituximab
*Trimethoprim-Sulfamethoxazole (Bactrim DS) (dose not specified) PO three times per week during and for 6 months after treatment
*Acyclovir (Zovirax) 800 mg PO once per day during and for 6 months after treatment
28-day cycle for up to 6 cycles
===References===
# 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 EuroPMC
==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====
*Ofatumumab (Arzerra) 300 mg IV once on day 1, then 1000 mg IV once per day on days 8, 15, 22
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====
*Ofatumumab (Arzerra) 300 mg IV once on day 1, then 2000 mg IV once per day on days 8, 15, 22, 29
5-week course
===References===
# 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 EuroPMC 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 	Longer TTF
====Targeted therapy====
*Rituximab (Rituxan) 375 mg/m2 IV once on day -1
====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 2 mg) IV once on day 1
====Glucocorticoid therapy====
*Prednisone (Sterapred) 100 mg/m2 PO once per day on days 1 to 5
21-day cycle for 4 to 8 cycles
===References===
# 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 EuroPMC
==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===
# 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 EuroPMC NCT00142116
==Thioguanine monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Weiss et al. 1963	1962 	Pilot
====Chemotherapy====
*Thioguanine (Tabloid) 75 mg PO once per day
Continued indefinitely
===References===
# 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 EuroPMC
=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====
*1 L of normal saline, prior to alemtuzumab
*Acetaminophen (Tylenol) 650 mg PO once per day on days 1, 3, 5, prior to alemtuzumab
*Diphenhydramine (Benadryl) 50 mg IV once per day on days 1, 3, 5, prior to alemtuzumab
*Hydrocortisone (Cortef) 100 to 200 mg IV once per day on days 1, 3, 5, prior to alemtuzumab if patient had a prior reaction
*Cimetidine (Tagamet) 300 mg IV once per day on days 1, 3, 5, prior to alemtuzumab if patient had a prior reaction
*Famciclovir (Famvir) 250 mg PO twice per day "or the equivalent" during treatment and for 3 months afterwards
*Trimethoprim-Sulfamethoxazole (Bactrim DS) PO twice per day three times per week during treatment and for 3 months afterwards
**Dapsone (Aczone) (dose not specified) instead, for patients with sulfur allergy
7-day cycle for 13 cycles
===References===
# 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 EuroPMC
# 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 EuroPMC 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====
*Bortezomib (Velcade) 1.3 mg/m2 IV once per day on days 1, 4, 8, 11
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====
*Bortezomib (Velcade) 1.3 mg/m2 IV once per day on days 1, 4, 8, 11
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====
*Bortezomib (Velcade) 1.3 mg/m2 IV once per day on days 1, 4, 8, 11
21-day cycles until PD or 2 cycles past CR or stable PR
===References===
# 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 EuroPMC
# 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 EuroPMC NCT00045695
# 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 EuroPMC
==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====
*Bortezomib (Velcade) 1.6 mg/m2 IV once per day on days 1, 8, 15
*Rituximab (Rituxan) as follows:
**Cycles 1 & 4: 375 mg/m2 IV once per day on days 1, 8, 15, 22
====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===
# 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 EuroPMC NCT00422799
## 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 EuroPMC
==Cladribine & Rituximab==
===Regimen===
Study 	Dates of enrollment	Evidence
Laszlo et al. 2010	2003-12 to 2007-02 	Phase 2
====Chemotherapy====
*Cladribine (Leustatin) 0.1 mg/kg SC once per day on days 1 to 5
====Targeted therapy====
*Rituximab (Rituxan) 375 mg/m2 IV once on day 1
1-month cycle for 4 cycles
===References===
# 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 EuroPMC 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====
*Ofatumumab (Arzerra) 300 mg IV once on day 1, then 1000 mg IV once per day on days 8, 15, 22
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====
*Ofatumumab (Arzerra) 300 mg IV once on day 1, then 2000 mg IV once per day on days 8, 15, 22, 29
5-week course
===References===
# 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 EuroPMC 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====
*Panobinostat (Farydak) 30 mg PO 3 days per week (Mondays, Wednesdays, and Fridays)
28-day cycles
	
===References===
# 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 EuroPMC NCT00936611
Category:Waldenström macroglobulinemia regimens
Category:Historical regimens
Category:Disease-specific pages
Category:Indolent lymphomas