Waldenström macroglobulinemia - historical
The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only.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
- 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 PubMed 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 PubMed
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 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
- 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 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
- 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 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
- 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 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
- 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 |
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 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
- 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 PubMed
- 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
- 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 PubMed
- 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
- 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
- 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 PubMed 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 PubMed
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 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
- 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 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
- 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 PubMed NCT00936611