Difference between revisions of "Waldenström macroglobulinemia"

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|-
 
|}
 
|}
−
 
 
====Chemotherapy====
 
====Chemotherapy====
 
''Note: the bendamustine infusion instructions are for the Treanda formulation, which was discontinued on 3/31/2016.''
 
''Note: the bendamustine infusion instructions are for the Treanda formulation, which was discontinued on 3/31/2016.''
−
*[[Bendamustine]] 90 mg/m2 IV over 30 to 60 minutes once on days 1 & 2
+
*[[Bendamustine]] 90 mg/m<sup>2</sup> IV over 30 to 60 minutes once per day on days 1 & 2
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
  
 
====Supportive medications====  
 
====Supportive medications====  
Line 54: Line 53:
 
*Prophylactic use of [[Filgrastim (Neupogen)|G-CSF]] allowed according [http://jop.ascopubs.org/content/2/4/196.full ASCO guidelines] (2006)
 
*Prophylactic use of [[Filgrastim (Neupogen)|G-CSF]] allowed according [http://jop.ascopubs.org/content/2/4/196.full ASCO guidelines] (2006)
  
−
'''28-day cycles x 6 cycles; Rummel et al. 2012 gave 2 additional cycles of rituximab only'''
+
'''28-day cycle for 6 cycles; Rummel et al. 2012 gave 2 additional cycles of rituximab only'''
  
 
''Patients in '''MAINTAIN''' were randomized to observation versus rituximab maintenance. Results have not yet been announced.''
 
''Patients in '''MAINTAIN''' were randomized to observation versus rituximab maintenance. Results have not yet been announced.''
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|}
 
|}
 
''This regimen was intended for patients ≥ 18 years old with previously untreated WM and an [[Performance_status#ECOG_performance_status_.28WHO.2FZubrod_score.29|Eastern Cooperative Oncology Group (ECOG) performance status]] score ≤ 2.''
 
''This regimen was intended for patients ≥ 18 years old with previously untreated WM and an [[Performance_status#ECOG_performance_status_.28WHO.2FZubrod_score.29|Eastern Cooperative Oncology Group (ECOG) performance status]] score ≤ 2.''
−
 
+
====Chemotherapy====
 
*[[Chlorambucil (Leukeran)]] as follows:
 
*[[Chlorambucil (Leukeran)]] as follows:
−
**Age ≤ 75 years: 8 mg/m2 PO once per day on days 1 to 10
+
**Age ≤ 75 years: 8 mg/m<sup>2</sup> PO once per day on days 1 to 10
−
**Age > 75 years: 6 mg/m2 PO once per day on days 1 to 10
+
**Age > 75 years: 6 mg/m<sup>2</sup> PO once per day on days 1 to 10
  
 
====Supportive medications====
 
====Supportive medications====
Line 104: Line 103:
 
**[[Pentamidine (Nebupent)]] 300 mg inhaled once per month
 
**[[Pentamidine (Nebupent)]] 300 mg inhaled once per month
  
−
'''28-day cycle x up to 12 cycles'''
+
'''28-day cycle for up to 12 cycles'''
  
 
===References===
 
===References===
Line 139: Line 138:
 
|}
 
|}
 
''This regimen was intended for patients ≥ 18 years old with previously untreated WM and an [[Performance_status#ECOG_performance_status_.28WHO.2FZubrod_score.29|Eastern Cooperative Oncology Group (ECOG) performance status]] score ≤ 2.''
 
''This regimen was intended for patients ≥ 18 years old with previously untreated WM and an [[Performance_status#ECOG_performance_status_.28WHO.2FZubrod_score.29|Eastern Cooperative Oncology Group (ECOG) performance status]] score ≤ 2.''
−
 
+
====Chemotherapy====
 
*[[Fludarabine (Fludara)]] as follows:
 
*[[Fludarabine (Fludara)]] as follows:
−
**Age ≤ 75 years: 40 mg/m2 PO once per day on days 1 to 5
+
**Age ≤ 75 years: 40 mg/m<sup>2</sup> PO once per day on days 1 to 5
−
**Age > 75 years: 30 mg/m2 PO once per day on days 1 to 5
+
**Age > 75 years: 30 mg/m<sup>2</sup> PO once per day on days 1 to 5
  
 
====Supportive medications====
 
====Supportive medications====
Line 152: Line 151:
 
**[[Acyclovir (Zovirax)]] 200 to 400 mg PO BID  
 
**[[Acyclovir (Zovirax)]] 200 to 400 mg PO BID  
  
−
'''28-day cycle x up to 6 cycles'''
+
'''28-day cycle for up to 6 cycles'''
  
 
===References===
 
===References===
Line 186: Line 185:
 
|-
 
|-
 
|}
 
|}
−
 
+
====Chemotherapy====
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV once on day 1
+
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m2 IV once on day 1
+
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
−
*[[Vincristine (Oncovin)]] 1.4 mg/m2 IV once on day 1
+
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> IV once on day 1
 
*[[Prednisone (Sterapred)]] 100 mg once per day on days 1 to 5
 
*[[Prednisone (Sterapred)]] 100 mg once per day on days 1 to 5
  
−
'''21-day cycle up to maximum of 6 cycles'''
+
'''21-day cycle for up to maximum of 6 cycles'''
  
 
===References===
 
===References===
Line 224: Line 223:
  
 
''Treon et al. 2009 did not clearly indicate the schedule for bortezomib, but it is inferred that this is what was meant.''
 
''Treon et al. 2009 did not clearly indicate the schedule for bortezomib, but it is inferred that this is what was meant.''
−
*[[Bortezomib (Velcade)]] 1.3 mg/m2 IV once on days 1, 4, 8, 11
+
====Chemotherapy====
−
*[[Dexamethasone (Decadron)]] 40 mg IV once on days 1, 4, 8, 11
+
*[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> IV once per day on days 1, 4, 8, 11
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 11
+
*[[Dexamethasone (Decadron)]] 40 mg IV once per day on days 1, 4, 8, 11
 +
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 11
  
 
====Supportive medications====
 
====Supportive medications====
Line 253: Line 253:
  
 
''The schedule for this regimen is confusing. Please see original reference.''
 
''The schedule for this regimen is confusing. Please see original reference.''
−
 
+
====Chemotherapy====
 
*[[Bortezomib (Velcade)]] as follows:
 
*[[Bortezomib (Velcade)]] as follows:
−
**Cycle 1: 1.3 mg/m2 IV once on days 1, 4, 8, 11
+
**Cycle 1: 1.3 mg/m<sup>2</sup> IV once per day on days 1, 4, 8, 11
−
**Cycles 2 to 5: 1.6 mg/m2 IV once per week on days 1, 8, 15, 22
+
**Cycles 2 to 5: 1.6 mg/m<sup>2</sup> IV once per week on days 1, 8, 15, 22
 
*[[Dexamethasone (Decadron)]] as follows:
 
*[[Dexamethasone (Decadron)]] as follows:
 
**Cycles 2 and 5 only: 40 mg IV once per week on days 1, 8, 15, 22
 
**Cycles 2 and 5 only: 40 mg IV once per week on days 1, 8, 15, 22
 
*[[Rituximab (Rituxan)]] as follows:
 
*[[Rituximab (Rituxan)]] as follows:
−
**Cycles 2 and 5 only: 375 mg/m2 IV once per week on days 1, 8, 15, 22
+
**Cycles 2 and 5 only: 375 mg/m<sup>2</sup> IV once per week on days 1, 8, 15, 22
  
 
====Supportive medications====
 
====Supportive medications====
Line 267: Line 267:
 
*[[Valacyclovir (Valtrex)]] or [[Acyclovir (Zovirax)]] (doses not specified) mandated for VZV prophylaxis
 
*[[Valacyclovir (Valtrex)]] or [[Acyclovir (Zovirax)]] (doses not specified) mandated for VZV prophylaxis
  
−
'''35-day cycle x 5 cycles (Cycle 1 is a 21-day cycle)'''
+
'''35-day cycle for 5 cycles (Cycle 1 is a 21-day cycle)'''
  
 
===References===
 
===References===
Line 293: Line 293:
 
|-
 
|-
 
|}
 
|}
−
 
+
====Chemotherapy====
−
*[[Bortezomib (Velcade)]] 1.6 mg/m2 IV once per week on days 1, 8, 15
+
*[[Bortezomib (Velcade)]] 1.6 mg/m<sup>2</sup> IV once per week on days 1, 8, 15
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once per week on days 1, 8, 15, 22 of cycles 1 and 4 only
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per week on days 1, 8, 15, 22 of cycles 1 and 4 only
  
 
====Supportive medications====
 
====Supportive medications====
 
*"Antiviral prophylaxis was recommended in all patients prior to initiation of therapy and for 3 months after completion of the six cycles."
 
*"Antiviral prophylaxis was recommended in all patients prior to initiation of therapy and for 3 months after completion of the six cycles."
  
−
'''28-day cycles x up to 6 cycles'''
+
'''28-day cycle for up to 6 cycles'''
  
 
===References===
 
===References===
Line 326: Line 326:
 
|-
 
|-
 
|}
 
|}
−
 
+
====Chemotherapy====
 
*[[Carfilzomib (Kyprolis)]] as follows:
 
*[[Carfilzomib (Kyprolis)]] as follows:
−
**Cycle 1: 20 mg/m2 IV over 20 minutes once per day on days 1, 2, 8, 9  
+
**Cycle 1: 20 mg/m<sup>2</sup> IV over 20 minutes once per day on days 1, 2, 8, 9  
−
**Subsequent cycles: 36 mg/m2 IV over 30 minutes once on days 1, 2, 8, 9
+
**Subsequent cycles: 36 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1, 2, 8, 9
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once per day on days 2 & 9, given after carfilzomib and dexamethasone
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 2 & 9, given after carfilzomib and dexamethasone
 
*[[Dexamethasone (Decadron)]] 20 mg IV once per day on days 1, 2, 8, 9
 
*[[Dexamethasone (Decadron)]] 20 mg IV once per day on days 1, 2, 8, 9
  
Line 339: Line 339:
 
*Prophylactic plasmapheresis and hold on rituximab was recommended for patients demonstrating an IgM level of ≥ 4,000 mg/dL
 
*Prophylactic plasmapheresis and hold on rituximab was recommended for patients demonstrating an IgM level of ≥ 4,000 mg/dL
  
−
'''21-day cycle x 6 cycles'''
+
'''21-day cycle for 6 cycles'''
  
 
''Patients with stable disease or better began [[Waldenström_macroglobulinemia#CaRD_2|CaRD maintenance]] 8 weeks later.''
 
''Patients with stable disease or better began [[Waldenström_macroglobulinemia#CaRD_2|CaRD maintenance]] 8 weeks later.''
Line 367: Line 367:
 
|-
 
|-
 
|}
 
|}
−
 
+
====Chemotherapy====
 
*[[Cladribine (Leustatin)]] 0.1 mg/kg SC once per day on days 1 to 5
 
*[[Cladribine (Leustatin)]] 0.1 mg/kg SC once per day on days 1 to 5
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
  
−
'''Monthly cycles x 4 cycles'''
+
'''Monthly cycle for 4 cycles'''
  
 
===References===
 
===References===
Line 399: Line 399:
  
 
''Note: The body text of Dimopoulos et al 2007 said that the regimen is given for "six courses," whereas the abstract says that it is given for 6 months."''
 
''Note: The body text of Dimopoulos et al 2007 said that the regimen is given for "six courses," whereas the abstract says that it is given for 6 months."''
 +
====Chemotherapy====
 +
*[[Dexamethasone (Decadron)]] 20 mg IV once on day 1, '''given first'''
 +
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1, '''given after [[Dexamethasone (Decadron)]]'''
 +
*[[Cyclophosphamide (Cytoxan)]] 100 mg/m<sup>2</sup> PO BID on days 1 to 5 (total dose per cycle: 1,000 mg/m2)
  
−
*[[Dexamethasone (Decadron)]] 20 mg IV once on day 1, given first
+
'''21-day cycle for 6 cycles'''
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1, given after [[Dexamethasone (Decadron)]]
 
−
*[[Cyclophosphamide (Cytoxan)]] 100 mg/m2 PO BID on days 1 to 5 (total dose per cycle: 1,000 mg/m2)
 
−
 
 
−
'''21-day cycles x 6 cycles'''
 
  
 
===References===
 
===References===
Line 410: Line 410:
 
## '''Update:''' '''Abstract:''' Dimopoulos, Meletios A., Roussou, Maria, Kastritis, Efstathios, Hadjiharissi, Evdoxia, Kyrtsonis, Marie-Christine, Symeonidis, Argiris, Repoussis, Panagiotis, Michalis, Eurydiki, Delimpasi, Sosana, Tsatalas, Konstantinos, Tsirigotis, Panagiotis, Vassou, Amalia, Vervessou, Elina, Katodritou, Eirini, Gavriatopoulou, Maria, Gika, Dimitra, Terpos, Evangelos, Zervas, Konstantinos. Primary Treatment of Waldenstrom's Macroglobulinemia with Dexamethasone, Rituximab and Cyclophosphamide (DRC): Final Analysis of a Phase II Study. ASH Annual Meeting Abstracts 2012 120: 438 [http://abstracts.hematologylibrary.org/cgi/content/abstract/120/21/438 link to abstract]
 
## '''Update:''' '''Abstract:''' Dimopoulos, Meletios A., Roussou, Maria, Kastritis, Efstathios, Hadjiharissi, Evdoxia, Kyrtsonis, Marie-Christine, Symeonidis, Argiris, Repoussis, Panagiotis, Michalis, Eurydiki, Delimpasi, Sosana, Tsatalas, Konstantinos, Tsirigotis, Panagiotis, Vassou, Amalia, Vervessou, Elina, Katodritou, Eirini, Gavriatopoulou, Maria, Gika, Dimitra, Terpos, Evangelos, Zervas, Konstantinos. Primary Treatment of Waldenstrom's Macroglobulinemia with Dexamethasone, Rituximab and Cyclophosphamide (DRC): Final Analysis of a Phase II Study. ASH Annual Meeting Abstracts 2012 120: 438 [http://abstracts.hematologylibrary.org/cgi/content/abstract/120/21/438 link to abstract]
  
−
==Everolimus {{#subobject:f542c8|Regimen=1}}==
+
==Everolimus (Afinitor) {{#subobject:f542c8|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
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|-
 
|-
 
|}
 
|}
 +
====Chemotherapy====
 
*[[Everolimus (Afinitor)]] 10 mg PO once per day
 
*[[Everolimus (Afinitor)]] 10 mg PO once per day
  
Line 459: Line 460:
 
|-
 
|-
 
|}
 
|}
−
 
+
====Chemotherapy====
−
*[[Fludarabine (Fludara)]] 25 mg/m2 IV once per day on days 2 to 4
+
*[[Fludarabine (Fludara)]] 25 mg/m<sup>2</sup> IV once per day on days 2 to 4
−
*[[Cyclophosphamide (Cytoxan)]] 250 mg/m2 IV once per day on days 2 to 4
+
*[[Cyclophosphamide (Cytoxan)]] 250 mg/m<sup>2</sup> IV once per day on days 2 to 4
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
  
 
====Supportive medications====
 
====Supportive medications====
Line 470: Line 471:
 
*[[Acyclovir (Zovirax)]] 800 mg PO once per day 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 x up to 6 cycles'''
+
'''28-day cycle for up to 6 cycles'''
  
 
===References===
 
===References===
Line 495: Line 496:
 
|-
 
|-
 
|}
 
|}
 +
====Chemotherapy====
 +
*[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> PO once per day on days 1 to 5
  
−
*[[Fludarabine (Fludara)]] 30 mg/m2 PO once per day on days 1 to 5
+
'''28-day cycle for 4 to 8 cycles'''
−
 
 
−
'''28-day cycles x 4 to 8 cycles'''
 
  
 
===References===
 
===References===
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|-
 
|-
 
|}
 
|}
−
 
+
====Chemotherapy====
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once per day on days 1, 8, 15, 22
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
  
 
'''4-week course'''
 
'''4-week course'''
Line 553: Line 554:
 
|-
 
|-
 
|}
 
|}
−
 
+
====Chemotherapy====
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once per week on weeks 2 to 5 and weeks 13 to 16 (8 doses total)
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per week on weeks 2 to 5 and weeks 13 to 16 (8 doses total)
 
*[[Thalidomide (Thalomid)]] as follows:
 
*[[Thalidomide (Thalomid)]] as follows:
 
**200 mg PO once per day x 2 weeks, then
 
**200 mg PO once per day x 2 weeks, then
Line 589: Line 590:
  
 
''Treatment preceded by [[Waldenström_macroglobulinemia#CaRD|CaRD induction]] x 6 cycles.''
 
''Treatment preceded by [[Waldenström_macroglobulinemia#CaRD|CaRD induction]] x 6 cycles.''
−
 
+
====Chemotherapy====
−
*[[Carfilzomib (Kyprolis)]] 36 mg/m2 IV once per day on days 1 & 2
+
*[[Carfilzomib (Kyprolis)]] 36 mg/m<sup>2</sup> IV once per day on days 1 & 2
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 2, given after carfilzomib and dexamethasone
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 2, given after carfilzomib and dexamethasone
 
*[[Dexamethasone (Decadron)]] 20 mg IV once per day on days 1 & 2
 
*[[Dexamethasone (Decadron)]] 20 mg IV once per day on days 1 & 2
  
−
'''8-week cycle x 8 cycles'''
+
'''8-week cycle for 8 cycles'''
  
 
===References===
 
===References===
Line 633: Line 634:
 
|}
 
|}
 
''This trial does not appear to have been published other than in abstract form, to our knowledge.''
 
''This trial does not appear to have been published other than in abstract form, to our knowledge.''
 +
====Chemotherapy====
 +
*[[Bendamustine]] 90 mg/m<sup>2</sup> IV once per day on days 1 & 2
 +
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
  
−
*[[Bendamustine]] 90 mg/m2 IV once per day on days 1 & 2
+
'''28-day cycle for up to 6 cycles'''
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
 
−
 
 
−
'''28-day cycle up to 6 cycles'''
 
  
 
===References===
 
===References===
Line 674: Line 675:
  
 
''This trial does not appear to have been published other than in abstract form, to our knowledge.''
 
''This trial does not appear to have been published other than in abstract form, to our knowledge.''
 +
====Chemotherapy====
 +
*[[Fludarabine (Fludara)]] 25 mg/m<sup>2</sup> (route not specified) once per day on days 1 to 3
 +
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
  
−
*[[Fludarabine (Fludara)]] 25 mg/m2 (route not specified) once per day on days 1 to 3
+
'''28-day cycle for up to 6 cycles'''
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
 
−
 
 
−
'''28-day cycle up to 6 cycles'''
 
  
 
===References===
 
===References===
Line 707: Line 708:
  
 
''Per the authors, "Alemtuzumab is an active therapy.., but short- and long-term toxicities need to be carefully weighed against other available treatment options."''
 
''Per the authors, "Alemtuzumab is an active therapy.., but short- and long-term toxicities need to be carefully weighed against other available treatment options."''
−
 
+
====Chemotherapy====
 
*[[Alemtuzumab (Campath)]] as follows:
 
*[[Alemtuzumab (Campath)]] as follows:
 
** 3 test doses of 3 mg IV, 10 mg IV, and 30 mg IV over 1 week
 
** 3 test doses of 3 mg IV, 10 mg IV, and 30 mg IV over 1 week
Line 747: Line 748:
 
|-
 
|-
 
|}
 
|}
−
 
+
====Chemotherapy====
−
*[[Bortezomib (Velcade)]] 1.3 mg/m2 IV once per day on days 1, 4, 8, 11
+
*[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> IV once per day on days 1, 4, 8, 11
  
 
'''Up to 8 cycles (cycle duration not defined)'''
 
'''Up to 8 cycles (cycle duration not defined)'''
Line 776: Line 777:
 
|-
 
|-
 
|}
 
|}
−
 
+
====Chemotherapy====
−
*[[Bortezomib (Velcade)]] 1.6 mg/m2 IV once per week on days 1, 8, 15
+
*[[Bortezomib (Velcade)]] 1.6 mg/m<sup>2</sup> IV once per week on days 1, 8, 15
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once per week on days 1, 8, 15, 22 of cycles 1 and 4 only
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per week on days 1, 8, 15, 22 of cycles 1 and 4 only
  
 
====Supportive medications====
 
====Supportive medications====
 
*"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."
 
*"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 x up to 6 cycles'''
+
'''28-day cycle for up to 6 cycles'''
  
 
===References===
 
===References===
Line 810: Line 811:
 
|-
 
|-
 
|}
 
|}
−
 
+
====Chemotherapy====
−
*[[Bendamustine]] 90 mg/m2 IV once per day on days 1 & 2
+
*[[Bendamustine]] 90 mg/m<sup>2</sup> IV once per day on days 1 & 2
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1 OR day 2
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1 OR day 2
  
 
'''28-day cycles'''
 
'''28-day cycles'''
Line 833: Line 834:
 
''Note: the bendamustine infusion instructions are for the Treanda formulation, which was discontinued on 3/31/2016.''
 
''Note: the bendamustine infusion instructions are for the Treanda formulation, which was discontinued on 3/31/2016.''
 
*[[Rituximab (Rituxan)]] as follows:
 
*[[Rituximab (Rituxan)]] as follows:
−
**One week prior to start of cycle 1: 375 mg/m2 IV once
+
**One week prior to start of cycle 1: 375 mg/m<sup>2</sup> IV once
−
**Cycles 1 to 4: 375 mg/m2 IV once on day 1
+
**Cycles 1 to 4: 375 mg/m<sup>2</sup> IV once on day 1
−
**4 weeks after cycle 4: 375 mg/m2 IV once
+
**4 weeks after cycle 4: 375 mg/m<sup>2</sup> IV once
−
*[[Bendamustine]] 90 mg/m2 IV over 30 minutes once per day on days 2 & 3
+
*[[Bendamustine]] 90 mg/m<sup>2</sup> IV over 30 minutes once per day on days 2 & 3
  
−
'''28-day cycle x 4 cycles'''
+
'''28-day cycle for 4 cycles'''
  
 
===References===
 
===References===
Line 864: Line 865:
 
|-
 
|-
 
|}
 
|}
−
 
+
====Chemotherapy====
 
*[[Cladribine (Leustatin)]] 0.1 mg/kg SC once per day on days 1 to 5
 
*[[Cladribine (Leustatin)]] 0.1 mg/kg SC once per day on days 1 to 5
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
  
−
'''Monthly cycles x 4 cycles'''
+
'''Monthly cycle for 4 cycles'''
  
 
===References===
 
===References===
Line 892: Line 893:
 
|-
 
|-
 
|}
 
|}
−
 
+
====Chemotherapy====
 
*[[Everolimus (Afinitor)]] 10 mg PO once per day while fasting
 
*[[Everolimus (Afinitor)]] 10 mg PO once per day while fasting
  
Line 924: Line 925:
 
|-
 
|-
 
|}
 
|}
−
 
+
====Chemotherapy====
 
*[[Ibrutinib (Imbruvica)]] 420 mg PO once per day
 
*[[Ibrutinib (Imbruvica)]] 420 mg PO once per day
  
Line 954: Line 955:
 
|-
 
|-
 
|}
 
|}
−
 
+
====Chemotherapy====
 
*[[Idelalisib (Zydelig)]] 150 mg PO BID
 
*[[Idelalisib (Zydelig)]] 150 mg PO BID
  
Line 985: Line 986:
  
 
''This study used two dosing schemas; per the authors, "A higher dose of OFA appeared to be more effective in pts previously exposed to [[Rituximab (Rituxan)|R]] or with baseline IgM = 4.0 g/dL. Further study of OFA in WM is warranted."''
 
''This study used two dosing schemas; per the authors, "A higher dose of OFA appeared to be more effective in pts previously exposed to [[Rituximab (Rituxan)|R]] or with baseline IgM = 4.0 g/dL. Further study of OFA in WM is warranted."''
−
 
+
====Chemotherapy====
 
*[[Ofatumumab (Arzerra)]] 300 mg IV once on week 1 and 1000 mg IV once per week on weeks 2 to 4 OR 300 mg IV once on week 1 and 2000 mg IV once per week on weeks 2 to 5
 
*[[Ofatumumab (Arzerra)]] 300 mg IV once on week 1 and 1000 mg IV once per week on weeks 2 to 4 OR 300 mg IV once on week 1 and 2000 mg IV once per week on weeks 2 to 5
  
Line 1,012: Line 1,013:
 
|-
 
|-
 
|}
 
|}
−
 
+
====Chemotherapy====
 
*[[Panobinostat (Farydak)]] 30 mg PO 3 days per week (Mondays, Wednesdays, and Fridays)
 
*[[Panobinostat (Farydak)]] 30 mg PO 3 days per week (Mondays, Wednesdays, and Fridays)
  
Line 1,040: Line 1,041:
 
|-
 
|-
 
|}
 
|}
−
 
+
====Chemotherapy====
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once per day on days 1, 8, 15, 22
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
  
 
'''4-week course'''
 
'''4-week course'''
Line 1,069: Line 1,070:
 
|-
 
|-
 
|}
 
|}
−
''Doses are not described in the abstract.''
+
''These are the doses of the phase II portion of the study.''
 +
====Chemotherapy====
 +
*[[Everolimus (Afinitor)]] 10 mg PO once per day
 +
*[[Bortezomib (Velcade)]] 1.6 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 +
*[[Rituximab (Rituxan)]] as follows:
 +
**Cycles 1 & 4: 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
  
−
*[[Everolimus (Afinitor)]]
+
'''28-day cycle for 6 cycles'''
−
*[[Bortezomib (Velcade)]]
+
 
−
*[[Rituximab (Rituxan)]]
+
''Treatment was followed by [[#Everolimus_.28Afinitor.29_3|everolimus maintenance]].''
 +
 
 +
===References===
 +
# Ghobrial IM, Redd R, Armand P, Banwait R, Boswell E, Chuma S, Huynh D, Sacco A, Roccaro AM, Perilla-Glen A, Noonan K, MacNabb M, Leblebjian H, Warren D, Henrick P, Castillo JJ, Richardson PG, Matous J, Weller E, Treon SP. Phase I/II trial of everolimus in combination with bortezomib and rituximab (RVR) in relapsed/refractory Waldenstrom macroglobulinemia. Leukemia. 2015 Dec;29(12):2338-46. Epub 2015 Jul 3. [http://www.nature.com/leu/journal/v29/n12/full/leu2015164a.html link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/26139427 PubMed]
 +
 
 +
=Consolidation and/or maintenance after salvage therapy=
 +
 
 +
==Everolimus (Afinitor) {{#subobject:a81ea4|Regimen=1}}==
 +
{| class="wikitable" style="float:right; margin-left: 5px;"
 +
|-
 +
|[[#toc|back to top]]
 +
|}
 +
===Regimen {{#subobject:b686db|Variant=1}}===
 +
{| border="1" style="text-align:center;" !align="left"
 +
|'''Study'''
 +
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 +
|-
 +
|[http://jco.ascopubs.org/content/28/8/1408.long Ghobrial et al. 2010]
 +
|<span
 +
style="background:#EEEE00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Phase II</span>
 +
|-
 +
|}
 +
''Treatment preceded by [[#RVR|RVR]] x 6.''
 +
====Chemotherapy====
 +
*[[Everolimus (Afinitor)]] 10 mg PO once per day
  
−
'''6 cycles'''
+
'''Continued until progression'''
  
 
===References===
 
===References===
−
# Ghobrial IM, Redd R, Armand P, Banwait R, Boswell E, Chuma S, Huynh D, Sacco A, Roccaro AM, Perilla-Glen A, Noonan K, MacNabb M, Leblebjian H, Warren D, Henrick P, Castillo JJ, Richardson PG, Matous J, Weller E, Treon SP. Phase I/II trial of everolimus in combination with bortezomib and rituximab (RVR) in relapsed/refractory Waldenstrom macroglobulinemia. Leukemia. 2015 Dec;29(12):2338-46. Epub 2015 Jul 3. [http://www.nature.com/leu/journal/v29/n12/full/leu2015164a.html link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/26139427 PubMed]
+
# Ghobrial IM, Redd R, Armand P, Banwait R, Boswell E, Chuma S, Huynh D, Sacco A, Roccaro AM, Perilla-Glen A, Noonan K, MacNabb M, Leblebjian H, Warren D, Henrick P, Castillo JJ, Richardson PG, Matous J, Weller E, Treon SP. Phase I/II trial of everolimus in combination with bortezomib and rituximab (RVR) in relapsed/refractory Waldenstrom macroglobulinemia. Leukemia. 2015 Dec;29(12):2338-46. Epub 2015 Jul 3. [http://www.nature.com/leu/journal/v29/n12/full/leu2015164a.html link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/26139427 PubMed]
  
 
=Investigational agents=
 
=Investigational agents=

Revision as of 19:24, 29 June 2016

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Is there a regimen missing from this list? Would you like to share a different dosage/schedule or an additional reference for a regimen? Have you noticed an error? Do you have an idea that will help the site grow to better meet your needs and the needs of many others? You are invited to contribute to the site.

39 regimens on this page
48 variants on this page


Untreated, randomized data

BR

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BR: Bendamustine, Rituximab

Regimen

Study Evidence Comparator
Rummel et al. 2012 (StiL NHL 7-–2008 –MAINTAIN) Non-randomized
Rummel et al. 2013 (StiL NHL1) Phase III, <20 pts in this subgroup R-CHOP

Chemotherapy

Note: the bendamustine infusion instructions are for the Treanda formulation, which was discontinued on 3/31/2016.

Supportive medications

  • Antiemetics, antipyretics, and antibiotics according to local standard of care
  • Prophylactic use of G-CSF allowed according ASCO guidelines (2006)

28-day cycle for 6 cycles; Rummel et al. 2012 gave 2 additional cycles of rituximab only

Patients in MAINTAIN were randomized to observation versus rituximab maintenance. Results have not yet been announced.

References

  1. Abstract: Rummel, Mathias J., Lerchenmuller, Christian, Greil, Richard, Gorner, Martin, Hensel, Manfred, Engel, Erik, Jaeger, Ulrich, Breuer, Friedhelm, Hertenstein, Bernd, Prummer, Otto, Buske, Christian, Barth, Juergen, Burchardt, Alexander C., Brugger, Wolfram. Bendamustin-Rituximab Induction Followed by Observation or Rituximab Maintenance for Newly Diagnosed Patients with Waldenstrom's Macroglobulinemia: Results From a Prospective, Randomized, Multicenter Study (StiL NHL 7-2008 -MAINTAIN-; ClinicalTrials.gov Identifier: NCT00877214). ASH Annual Meeting Abstracts 2012 120: 2739 link to abstract
  2. Rummel MJ, Niederle N, Maschmeyer G, Banat GA, von Grünhagen U, Losem C, Kofahl-Krause D, Heil G, Welslau M, Balser C, Kaiser U, Weidmann E, Dürk H, Ballo H, Stauch M, Roller F, Barth J, Hoelzer D, Hinke A, Brugger W; on behalf of the Study group indolent Lymphomas (StiL). Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trial. Lancet. 2013 Apr 6;381(9873):1203-10. Epub 2013 Feb 20. Erratum in: Lancet. 2013 Apr 6;381(9873):1184. link to original article contains verified protocol PubMed
    1. Update: Abstract: Mathias J. Rummel, MD, Georg Maschmeyer, MD, Arnold Ganser, Andrea Heider, PhD, Ulrich von Grünhagen, MD, PhD5, Christoph Losem, Gerhard Heil, MD, Manfred Welslau, Christina Balser, MD, Ulrich Kaiser, MD, Eckhart Weidmann, Heinz Dürk, MD, Hans Peter Böck, Martina Beate Stauch, MD, Jürgen Barth, Wolfgang Blau, MD, Alexander Burchardt, MD, Frank Kauff, PhD, Axel Hinke, PhD and Wolfram Brugger, MD. Bendamustine Plus Rituximab (B-R) Versus CHOP Plus Rituximab (CHOP-R) As First-Line Treatment in Patients with Indolent and Mantle Cell Lymphomas (MCL) – 7 Year Updated Results from the StiL NHL1 Study. ASH Annual Meeting 2014, Abstract 4407 link to abstract

Chlorambucil (Leukeran)

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Regimen

Study Evidence Comparator Efficacy
Leblond et al. 2012 (WM1) Phase III Fludarabine Inferior OS

This regimen was intended for patients ≥ 18 years old with previously untreated WM and an Eastern Cooperative Oncology Group (ECOG) performance status score ≤ 2.

Chemotherapy

  • Chlorambucil (Leukeran) as follows:
    • Age ≤ 75 years: 8 mg/m2 PO once per day on days 1 to 10
    • Age > 75 years: 6 mg/m2 PO once per day on days 1 to 10

Supportive medications

28-day cycle for up to 12 cycles

References

  1. Leblond V, Johnson S, Chevret S, Copplestone A, Rule S, Tournilhac O, Seymour JF, Patmore RD, Wright D, Morel P, Dilhuydy MS, Willoughby S, Dartigeas C, Malphettes M, Royer B, Ewings M, Pratt G, Lejeune J, Nguyen-Khac F, Choquet S, Owen RG. Results of a randomized trial of chlorambucil versus fludarabine for patients with untreated waldenstrom macroglobulinemia, marginal zone lymphoma, or lymphoplasmacytic lymphoma. J Clin Oncol. 2013 Jan 20;31(3):301-7. Epub 2012 Dec 10. link to original article contains verified protocol PubMed

Fludarabine (Fludara)

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Regimen

Study Evidence Comparator Efficacy
Leblond et al. 2012 (WM1) Phase III Chlorambucil Superior OS

This regimen was intended for patients ≥ 18 years old with previously untreated WM and an Eastern Cooperative Oncology Group (ECOG) performance status score ≤ 2.

Chemotherapy

  • Fludarabine (Fludara) as follows:
    • Age ≤ 75 years: 40 mg/m2 PO once per day on days 1 to 5
    • Age > 75 years: 30 mg/m2 PO once per day on days 1 to 5

Supportive medications

28-day cycle for up to 6 cycles

References

  1. Leblond V, Johnson S, Chevret S, Copplestone A, Rule S, Tournilhac O, Seymour JF, Patmore RD, Wright D, Morel P, Dilhuydy MS, Willoughby S, Dartigeas C, Malphettes M, Royer B, Ewings M, Pratt G, Lejeune J, Nguyen-Khac F, Choquet S, Owen RG. Results of a randomized trial of chlorambucil versus fludarabine for patients with untreated waldenstrom macroglobulinemia, marginal zone lymphoma, or lymphoplasmacytic lymphoma. J Clin Oncol. 2013 Jan 20;31(3):301-7. Epub 2012 Dec 10. link to original article contains verified protocol PubMed

R-CHOP

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

Synonyms: R-CHOP-21, CHOP-R

Structured Concept: C9760 (NCI-T), C0393023 (NCI-MT/UMLS)

R-CHOP is not considered a standard regimen for WM, but was used as the comparator arm in the StiL NHL1 trial and is reported here.

Regimen

Study Evidence Comparator
Rummel et al. 2013 (StiL NHL1) Phase III, <20 pts in this subgroup BR

Chemotherapy

21-day cycle for up to maximum of 6 cycles

References

  1. Rummel MJ, Niederle N, Maschmeyer G, Banat GA, von Grünhagen U, Losem C, Kofahl-Krause D, Heil G, Welslau M, Balser C, Kaiser U, Weidmann E, Dürk H, Ballo H, Stauch M, Roller F, Barth J, Hoelzer D, Hinke A, Brugger W; on behalf of the Study group indolent Lymphomas (StiL). Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trial. Lancet. 2013 Apr 6;381(9873):1203-10. Epub 2013 Feb 20. Erratum in: Lancet. 2013 Apr 6;381(9873):1184. link to original article contains verified protocol PubMed
    1. Update: Abstract: Mathias J. Rummel, MD, Georg Maschmeyer, MD, Arnold Ganser, Andrea Heider, PhD, Ulrich von Grünhagen, MD, PhD5, Christoph Losem, Gerhard Heil, MD, Manfred Welslau, Christina Balser, MD, Ulrich Kaiser, MD, Eckhart Weidmann, Heinz Dürk, MD, Hans Peter Böck, Martina Beate Stauch, MD, Jürgen Barth, Wolfgang Blau, MD, Alexander Burchardt, MD, Frank Kauff, PhD, Axel Hinke, PhD and Wolfram Brugger, MD. Bendamustine Plus Rituximab (B-R) Versus CHOP Plus Rituximab (CHOP-R) As First-Line Treatment in Patients with Indolent and Mantle Cell Lymphomas (MCL) – 7 Year Updated Results from the StiL NHL1 Study. ASH Annual Meeting 2014, Abstract 4407 link to abstract

Untreated, non-randomized or retrospective data

BDR

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BDR: Bortezomib, Dexamethasone, Rituximab

Regimen #1

Study Evidence
Treon et al. 2009 (WMCTG 05-180) Phase II

Treon et al. 2009 did not clearly indicate the schedule for bortezomib, but it is inferred that this is what was meant.

Chemotherapy

Supportive medications

  • Valacyclovir (Valtrex) 1 g PO once per day or Acyclovir (Zovirax) 400 mg PO twice per day recommended for shingles prophylaxis
  • "The use of diphenhydramine, acetaminophen and, at the treating physician's discretion, corticosteroids and/or ranitidine or cimetidine was permitted for rituximab infusion prophylaxis. Granulocyte colony-stimulating factor, erythropoietin, and transfusions of packed RBCs or platelets were permitted to support patient's counts during therapy."
  • "The prophylactic use of plasmapheresis was recommended for patients demonstrating an IgM level of = 5,000 mg/dL before the administration of rituximab, given the potential for rituximab-mediated IgM flare and aggravation of hyperviscosity."

4 cycles followed by a 12-week pause and then 4 additional cycles spaced 12 weeks apart

The authors advise this approach "in hopes of reducing the incidence of peripheral neuropathy". The length of the initial cycles was not specified in the paper.

Regimen #2

Study Evidence
Dimopoulos et al. 2013 Phase II

The schedule for this regimen is confusing. Please see original reference.

Chemotherapy

  • Bortezomib (Velcade) as follows:
    • Cycle 1: 1.3 mg/m2 IV once per day on days 1, 4, 8, 11
    • Cycles 2 to 5: 1.6 mg/m2 IV once per week on days 1, 8, 15, 22
  • Dexamethasone (Decadron) as follows:
    • Cycles 2 and 5 only: 40 mg IV once per week on days 1, 8, 15, 22
  • Rituximab (Rituxan) as follows:
    • Cycles 2 and 5 only: 375 mg/m2 IV once per week on days 1, 8, 15, 22

Supportive medications

35-day cycle for 5 cycles (Cycle 1 is a 21-day cycle)

References

  1. Treon SP, Ioakimidis L, Soumerai JD, Patterson CJ, Sheehy P, Nelson M, Willen M, Matous J, Mattern J 2nd, Diener JG, Keogh GP, Myers TJ, Boral A, Birner A, Esseltine DL, Ghobrial IM. Primary therapy of Waldenström macroglobulinemia with bortezomib, dexamethasone, and rituximab: WMCTG clinical trial 05-180. J Clin Oncol. 2009 Aug 10;27(23):3830-5. Epub 2009 Jun 8. link to original article contains verified protocol PubMed content property of HemOnc.org
  2. Dimopoulos MA, García-Sanz R, Gavriatopoulou M, Morel P, Kyrtsonis MC, Michalis E, Kartasis Z, Leleu X, Palladini G, Tedeschi A, Gika D, Merlini G, Kastritis E, Sonneveld P. Primary therapy of Waldenstrom's macroglobulinemia (WM) with weekly bortezomib, low-dose dexamethasone and rituximab (BDR): long term results of a phase II study of the European Myeloma Network (EMN). Blood. 2013 Nov 7;122(19):3276-82. Epub 2013 Sep 4. link to original article contains verified protocol PubMed

Bortezomib & Rituximab

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Regimen

Study Evidence
Ghobrial et al. 2010 Phase II

Chemotherapy

Supportive medications

  • "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. 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. link to original article contains verified protocol PubMed

CaRD

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CaRD: Carfilzomib, Rituximab, Dexamethasone

Regimen

Study Evidence
Treon et al. 2014 Phase II

Chemotherapy

  • Carfilzomib (Kyprolis) as follows:
    • Cycle 1: 20 mg/m2 IV over 20 minutes once per day on days 1, 2, 8, 9
    • Subsequent cycles: 36 mg/m2 IV over 30 minutes once per day on days 1, 2, 8, 9
  • Rituximab (Rituxan) 375 mg/m2 IV once per day on days 2 & 9, given after carfilzomib and dexamethasone
  • Dexamethasone (Decadron) 20 mg IV once per day on days 1, 2, 8, 9

Supportive medications

21-day cycle for 6 cycles

Patients with stable disease or better began CaRD maintenance 8 weeks later.

References

  1. Treon SP, Tripsas CK, Meid K, Kanan S, Sheehy P, Chuma S, Xu L, Cao Y, Yang G, Liu X, Patterson CJ, Warren D, Hunter ZR, Turnbull B, Ghobrial IM, Castillo JJ. Carfilzomib, rituximab, and dexamethasone (CaRD) treatment offers a neuropathy-sparing approach for treating Waldenström's macroglobulinemia. Blood. 2014 Jul 24;124(4):503-10. Epub 2014 May 23. link to original article contains verified protocol PubMed

Cladribine & Rituximab

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Regimen

Study Evidence
Laszlo et al. 2010 Phase II

Chemotherapy

Monthly 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 contains verified protocol PubMed

DRC

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DRC: Dexamethasone, Rituximab, Cyclophosphamide

Regimen

Study Evidence
Dimopoulos et al. 2007 Phase II

Note: The body text of Dimopoulos et al 2007 said that the regimen is given for "six courses," whereas the abstract says that it is given for 6 months."

Chemotherapy

21-day cycle for 6 cycles

References

  1. Dimopoulos MA, Anagnostopoulos A, Kyrtsonis MC, Zervas K, Tsatalas C, Kokkinis G, Repoussis P, Symeonidis A, Delimpasi S, Katodritou E, Vervessou E, Michali E, Pouli A, Gika D, Vassou A, Terpos E, Anagnostopoulos N, Economopoulos T, Pangalis G. Primary treatment of Waldenström macroglobulinemia with dexamethasone, rituximab, and cyclophosphamide. J Clin Oncol. 2007 Aug 1;25(22):3344-9. link to original article contains verified protocol PubMed
    1. Update: Abstract: Dimopoulos, Meletios A., Roussou, Maria, Kastritis, Efstathios, Hadjiharissi, Evdoxia, Kyrtsonis, Marie-Christine, Symeonidis, Argiris, Repoussis, Panagiotis, Michalis, Eurydiki, Delimpasi, Sosana, Tsatalas, Konstantinos, Tsirigotis, Panagiotis, Vassou, Amalia, Vervessou, Elina, Katodritou, Eirini, Gavriatopoulou, Maria, Gika, Dimitra, Terpos, Evangelos, Zervas, Konstantinos. Primary Treatment of Waldenstrom's Macroglobulinemia with Dexamethasone, Rituximab and Cyclophosphamide (DRC): Final Analysis of a Phase II Study. ASH Annual Meeting Abstracts 2012 120: 438 link to abstract

Everolimus (Afinitor)

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Regimen

Study Evidence
Treon et al. 2011 Phase II

Chemotherapy

28-day cycles, given until progression or unacceptable toxicity

References

  1. Abstract: Treon, Steven P, Tripsas, Christina K, Ioakimidis, Leukothea, Warren, Diane, Patterson, Christopher, Heffner, Leonard, Eradat, Herbert, Gregory, Stephanie A., Thomas, Sheeba, Advani, Ranjana, Baz, Rachid, Badros, Ashraf Z., Matous, Jeffrey, Anderson, Kenneth C., Ghobrial, Irene M. Prospective, Multicenter Study of the MTOR Inhibitor Everolimus (RAD001) As Primary Therapy in Waldenstrom's Macroglobulinemia. ASH Annual Meeting Abstracts 2011 118: 2951 link to abstract
    1. Update: Abstract: Steven Peter Treon, MD, MA, PhD, Christina K Tripsas, Kirsten Meid, Christopher Patterson, Leonard T Heffner, Herbert Eradat, Stephanie A. Gregory, Sheeba K. Thomas, Ranjana H. Advani, Rachid Baz, Ashraf Z. Badros, Jeffrey Matous, Timothy J. Murphy, Irene M. Ghobrial. Prospective, Multicenter Study Of The Mtor Inhibitor Everolimus (RAD001) As Primary Therapy In Waldenstrom’s Macroglobulinemia. Blood Nov 2013,122(21)1822 link to abstract

FCR

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FCR: Fludarabine, Cyclophosphamide, Rituximab

Regimen

Study Evidence
Tedeschi et al. 2011 Phase II

Chemotherapy

Supportive medications

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 contains verified protocol PubMed

Fludarabine (Fludara)

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Regimen

Study Evidence
Dhodapkar et al. 2001 (S9003) Phase II

Chemotherapy

28-day cycle for 4 to 8 cycles

References

  1. Dhodapkar MV, Jacobson JL, Gertz MA, Rivkin SE, Roodman GD, Tuscano JM, Shurafa M, Kyle RA, Crowley JJ, Barlogie B. Prognostic factors and response to fludarabine therapy in patients with Waldenström macroglobulinemia: results of United States intergroup trial (Southwest Oncology Group S9003). Blood. 2001 Jul 1;98(1):41-8. link to original article contains verified protocol PubMed
    1. Update: Dhodapkar MV, Jacobson JL, Gertz MA, Crowley JJ, Barlogie B. Prognostic factors and response to fludarabine therapy in Waldenstrom's macroglobulinemia: an update of a US intergroup trial (SW0G S9003). Semin Oncol. 2003 Apr;30(2):220-5. PubMed
    2. Update: Dhodapkar MV, Hoering A, Gertz MA, Rivkin S, Szymonifka J, Crowley J, Barlogie B. Long-term survival in Waldenstrom macroglobulinemia: 10-year follow-up of Southwest Oncology Group-directed intergroup trial S9003. Blood. 2009 Jan 22;113(4):793-6. Epub 2008 Oct 17. link to original article PubMed

Rituximab (Rituxan)

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Regimen

Study Evidence
Gertz et al. 2004 (ECOG E3A98) Phase II

Chemotherapy

4-week course

References

  1. Gertz MA, Rue M, Blood E, Kaminer LS, Vesole DH, Greipp PR. Multicenter phase 2 trial of rituximab for Waldenström macroglobulinemia (WM): an Eastern Cooperative Oncology Group Study (E3A98). Leuk Lymphoma. 2004 Oct;45(10):2047-55. link to original article contains protocol PubMed

Rituximab & Thalidomide

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Regimen

Study Evidence
Treon et al. 2008 Phase II

Chemotherapy

  • Rituximab (Rituxan) 375 mg/m2 IV once per week on weeks 2 to 5 and weeks 13 to 16 (8 doses total)
  • Thalidomide (Thalomid) as follows:
    • 200 mg PO once per day x 2 weeks, then
    • 400 mg PO once per day x 50 weeks

52-week course

References

  1. 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 contains verified protocol PubMed

Consolidation and/or maintenance after upfront therapy

CaRD

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CaRD: Carfilzomib, Rituximab, Dexamethasone

Regimen

Study Evidence
Treon et al. 2014 Phase II

Treatment preceded by CaRD induction x 6 cycles.

Chemotherapy

8-week cycle for 8 cycles

References

  1. Treon SP, Tripsas CK, Meid K, Kanan S, Sheehy P, Chuma S, Xu L, Cao Y, Yang G, Liu X, Patterson CJ, Warren D, Hunter ZR, Turnbull B, Ghobrial IM, Castillo JJ. Carfilzomib, rituximab, and dexamethasone (CaRD) treatment offers a neuropathy-sparing approach for treating Waldenström's macroglobulinemia. Blood. 2014 Jul 24;124(4):503-10. Epub 2014 May 23. link to original article contains verified protocol PubMed

Relapsed/refractory, randomized data

BR

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BR: Bendamustine, Rituximab

Regimen

Study Evidence Comparator Efficacy
Rummel et al. 2010 (NHL 2-2003) Phase III Fludarabine & Rituximab Increased OS

This trial does not appear to have been published other than in abstract form, to our knowledge.

Chemotherapy

28-day cycle for up to 6 cycles

References

  1. Abstract: Mathias J. Rummel, MD, PhD, Ulrich Kaiser, MD, Christina Balser, Martina Beate Stauch, Wolfram Brugger, MD, PhD, Manfred Welslau, Norbert Niederle, Christoph Losem, Harald Ballo, Eckhart Weidmann, Ulrich von Gruenhagen, Lothar Mueller, Michael Sandherr, MD, Julia Vereschagina, Axel Hinke and Juergen Barth. Bendamustine Plus Rituximab Versus Fludarabine Plus Rituximab In Patients with Relapsed Follicular, Indolent and Mantle Cell Lymphomas – Final Results of the Randomized Phase III Study NHL 2-2003 on Behalf of the StiL (Study Group Indolent Lymphomas, Germany). ASH Annual Meeting 2010, Abstract 856 link to abstract
    1. Update: Abstract: Mathias J. Rummel, MD, Christina Balser, MD, Ulrich Kaiser, MD, Hans Peter Böck, Martina Beate Stauch, MD, Andrea Heider, PhD, Manfred Welslau, Christoph Losem, Eckhart Weidmann, Wolfgang Blau, MD, Alexander Burchardt, MD, Jürgen Barth, Frank Kauff, PhD, Axel Hinke, PhD and Wolfram Brugger, MD. Bendamustine Plus Rituximab Versus Fludarabine Plus Rituximab in Patients with Relapsed Follicular, Indolent, or Mantle Cell Lymphomas – 8-Year Follow-up Results of the Randomized Phase III Study NHL 2-2003 on Behalf of the StiL (Study Group Indolent Lymphomas, Germany). ASH Annual Meeting 2014, Abstract 145 link to abstract

Fludarabine & Rituximab

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Regimen

Study Evidence Comparator Efficacy
Rummel et al. 2010 (NHL 2-2003) Phase III BR Decreased OS

This trial does not appear to have been published other than in abstract form, to our knowledge.

Chemotherapy

28-day cycle for up to 6 cycles

References

  1. Abstract: Mathias J. Rummel, MD, PhD, Ulrich Kaiser, MD, Christina Balser, Martina Beate Stauch, Wolfram Brugger, MD, PhD, Manfred Welslau, Norbert Niederle, Christoph Losem, Harald Ballo, Eckhart Weidmann, Ulrich von Gruenhagen, Lothar Mueller, Michael Sandherr, MD, Julia Vereschagina, Axel Hinke and Juergen Barth. Bendamustine Plus Rituximab Versus Fludarabine Plus Rituximab In Patients with Relapsed Follicular, Indolent and Mantle Cell Lymphomas – Final Results of the Randomized Phase III Study NHL 2-2003 on Behalf of the StiL (Study Group Indolent Lymphomas, Germany). ASH Annual Meeting 2010, Abstract 856 link to abstract
    1. Update: Abstract: Mathias J. Rummel, MD, Christina Balser, MD, Ulrich Kaiser, MD, Hans Peter Böck, Martina Beate Stauch, MD, Andrea Heider, PhD, Manfred Welslau, Christoph Losem, Eckhart Weidmann, Wolfgang Blau, MD, Alexander Burchardt, MD, Jürgen Barth, Frank Kauff, PhD, Axel Hinke, PhD and Wolfram Brugger, MD. Bendamustine Plus Rituximab Versus Fludarabine Plus Rituximab in Patients with Relapsed Follicular, Indolent, or Mantle Cell Lymphomas – 8-Year Follow-up Results of the Randomized Phase III Study NHL 2-2003 on Behalf of the StiL (Study Group Indolent Lymphomas, Germany). ASH Annual Meeting 2014, Abstract 145 link to abstract

Relapsed/refractory, non-randomized or retrospective data

Alemtuzumab (Campath)

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Regimen

Study Evidence
Treon et al. 2011 Phase II

Per the authors, "Alemtuzumab is an active therapy.., but short- and long-term toxicities need to be carefully weighed against other available treatment options."

Chemotherapy

  • Alemtuzumab (Campath) as follows:
    • 3 test doses of 3 mg IV, 10 mg IV, and 30 mg IV over 1 week
    • 30 mg IV three times per week x 12 weeks (36 doses)

Supportive medications

13-week treatment course

References

  1. 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 contains verified protocol PubMed

Bortezomib (Velcade)

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Regimen

Study Evidence
Treon et al. 2007 (WMCTG 03-248) Phase II

Chemotherapy

Up to 8 cycles (cycle duration not defined)

References

  1. 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 contains verified protocol PubMed

Bortezomib & Rituximab

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Regimen

Study Evidence
Ghobrial et al. 2010 Phase II

Chemotherapy

Supportive medications

  • "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. 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 contains verified protocol PubMed

BR

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BR: Bendamustine, Rituximab

Regimen #1

Study Evidence
Treon et al. 2011 Phase II

Chemotherapy

28-day cycles

Regimen #2

Study Evidence
Rummel et al. 2005 Phase II, <20 patients in this subgroup

Chemotherapy

Note: the bendamustine infusion instructions are for the Treanda formulation, which was discontinued on 3/31/2016.

  • Rituximab (Rituxan) as follows:
    • One week prior to start of cycle 1: 375 mg/m2 IV once
    • Cycles 1 to 4: 375 mg/m2 IV once on day 1
    • 4 weeks after cycle 4: 375 mg/m2 IV once
  • Bendamustine 90 mg/m2 IV over 30 minutes once per day on days 2 & 3

28-day cycle for 4 cycles

References

  1. Rummel MJ, Al-Batran SE, Kim SZ, Welslau M, Hecker R, Kofahl-Krause D, Josten KM, Dürk H, Rost A, Neise M, von Grünhagen U, Chow KU, Hansmann ML, Hoelzer D, Mitrou PS. Bendamustine plus rituximab is effective and has a favorable toxicity profile in the treatment of mantle cell and low-grade non-Hodgkin's lymphoma. J Clin Oncol. 2005 May 20;23(15):3383-9. link to original article contains verified protocol PubMed
  2. Treon SP, Hanzis C, Tripsas C, Ioakimidis L, Patterson CJ, Manning RJ, Sheehy P. Bendamustine therapy in patients with relapsed or refractory Waldenström's macroglobulinemia. Clin Lymphoma Myeloma Leuk. 2011 Feb;11(1):133-5. link to original article contains protocol PubMed

Cladribine & Rituximab

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Regimen

Study Evidence
Laszlo et al. 2010 Phase II

Chemotherapy

Monthly 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 contains verified protocol PubMed

Everolimus (Afinitor)

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Regimen

Study Evidence
Ghobrial et al. 2010 Phase II

Chemotherapy

Supportive medications

  • WBC growth factors per physician discretion if neutropenia occurred, but it was not to be used prophylactically in order to maintain dosing.
  • for anemia allowed per physician discretion.

28-day cycles, given until progression or unacceptable toxicity

References

  1. Ghobrial IM, Gertz M, Laplant B, Camoriano J, Hayman S, Lacy M, Chuma S, Harris B, Leduc R, Rourke M, Ansell SM, Deangelo D, Dispenzieri A, Bergsagel L, Reeder C, Anderson KC, Richardson PG, Treon SP, Witzig TE. Phase II trial of the oral mammalian target of rapamycin inhibitor everolimus in relapsed or refractory Waldenstrom macroglobulinemia. J Clin Oncol. 2010 Mar 10;28(8):1408-14. Epub 2010 Feb 8. link to original article contains verified protocol PubMed

Ibrutinib (Imbruvica)

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Regimen

Study Evidence
Treon et al. 2015 Phase II

Chemotherapy

Continuously for 2 years or until progression or unacceptable toxicity

References

  1. Treon SP, Tripsas CK, Meid K, Warren D, Varma G, Green R, Argyropoulos KV, Yang G, Cao Y, Xu L, Patterson CJ, Rodig S, Zehnder JL, Aster JC, Harris NL, Kanan S, Ghobrial I, Castillo JJ, Laubach JP, Hunter ZR, Salman Z, Li J, Cheng M, Clow F, Graef T, Palomba ML, Advani RH. Ibrutinib in previously treated Waldenström's macroglobulinemia. N Engl J Med. 2015 Apr 9;372(15):1430-40. link to original article PubMed

Idelalisib (Zydelig)

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On 3/21/2016 Gilead announced that they were stopping seven clinical trials of idelalisib in patients with CLL, SLL, and iNHL due to excess deaths and increased rates of SAEs. A REMS program has also been announced.

Regimen

Study Evidence
Gopal et al. 2014 (DELTA) Phase II, <20 patients in this subgroup

Chemotherapy

Continued until progression, death, or unacceptable toxicity

References

  1. Gopal AK, Kahl BS, de Vos S, Wagner-Johnston ND, Schuster SJ, Jurczak WJ, Flinn IW, Flowers CR, Martin P, Viardot A, Blum KA, Goy AH, Davies AJ, Zinzani PL, Dreyling M, Johnson D, Miller LL, Holes L, Li D, Dansey RD, Godfrey WR, Salles GA. PI3Kd Inhibition by Idelalisib in Patients with Relapsed Indolent Lymphoma. N Engl J Med. 2014 Jan 22. link to original article contains verified protocol PubMed
    1. Update: Abstract: Ajay K. Gopal, MD, Brad S. Kahl, MD, Sven de Vos, MD, PhD, Nina D. Wagner-Johnston, MD, Stephen J. Schuster, MD, Wojciech Jurczak, MD, PhD, Ian W. Flinn, MD, PhD, Christopher R. Flowers, MD, Peter Martin, MD, Andreas Viardot, MD, Kristie A. Blum, MD, Andre Goy, MD, Andrew Davies, BM PhD, Pier Luigi Zinzani, MD, Martin H. Dreyling, MD, PhD, Leanne M. Holes, Bess Sorensen, PhD, Wayne R. Godfrey, MD and Gilles Andre Salles, MD, PhD. Mature Follow up from a Phase 2 Study of PI3K-Delta Inhibitor Idelalisib in Patients with Double (Rituximab and Alkylating agent)-Refractory Indolent B-Cell Non-Hodgkin Lymphoma (iNHL). ASH Annual Meeting 2014, Abstract 1708 link to abstract

Ofatumumab (Arzerra)

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Regimen

Study Evidence
Furman et al. 2011 Phase II

This study used two dosing schemas; per the authors, "A higher dose of OFA appeared to be more effective in pts previously exposed to R or with baseline IgM = 4.0 g/dL. Further study of OFA in WM is warranted."

Chemotherapy

  • Ofatumumab (Arzerra) 300 mg IV once on week 1 and 1000 mg IV once per week on weeks 2 to 4 OR 300 mg IV once on week 1 and 2000 mg IV once per week on weeks 2 to 5

4-week or 5-week course

References

  1. Abstract: Furman, Richard R., Eradat, Herbert, DiRienzo, Christine Gabriella, Hayman, Suzanne R, Hofmeister, Craig C., Avignon, Nathalie A., Leonard, John P., Coleman, Morton, Advani, Ranjana, Switzky, Julie C., Liao, Qiming, Shah, Damini N., Lisby, Steen, Lin, Thomas S. A Phase II Trial of Ofatumumab in Subjects with Waldenstrom's Macroglobulinemia. ASH Annual Meeting Abstracts 2011 118: 3701 link to abstract

Panobinostat (Farydak)

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Regimen

Study Evidence
Ghobrial et al. 2013 Phase II

Chemotherapy

28-day cycles, given until progression of disease

References

  1. 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 contains verified protocol PubMed

Rituximab (Rituxan)

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Regimen

Study Evidence
Gertz et al. 2004 (ECOG E3A98) Phase II

Chemotherapy

4-week course

References

  1. Gertz MA, Rue M, Blood E, Kaminer LS, Vesole DH, Greipp PR. Multicenter phase 2 trial of rituximab for Waldenström macroglobulinemia (WM): an Eastern Cooperative Oncology Group Study (E3A98). Leuk Lymphoma. 2004 Oct;45(10):2047-55. link to original article contains protocol PubMed

RVR

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RVR: RAD-001 (Everolimus), Velcade (Bortezomib), Rituximab

Regimen

Study Evidence
Ghobrial et al. 2015 Phase I/II

These are the doses of the phase II portion of the study.

Chemotherapy

28-day cycle for 6 cycles

Treatment was followed by everolimus maintenance.

References

  1. Ghobrial IM, Redd R, Armand P, Banwait R, Boswell E, Chuma S, Huynh D, Sacco A, Roccaro AM, Perilla-Glen A, Noonan K, MacNabb M, Leblebjian H, Warren D, Henrick P, Castillo JJ, Richardson PG, Matous J, Weller E, Treon SP. Phase I/II trial of everolimus in combination with bortezomib and rituximab (RVR) in relapsed/refractory Waldenstrom macroglobulinemia. Leukemia. 2015 Dec;29(12):2338-46. Epub 2015 Jul 3. link to original article contains verified protocol PubMed

Consolidation and/or maintenance after salvage therapy

Everolimus (Afinitor)

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Regimen

Study Evidence
Ghobrial et al. 2010 Phase II

Treatment preceded by RVR x 6.

Chemotherapy

Continued until progression

References

  1. Ghobrial IM, Redd R, Armand P, Banwait R, Boswell E, Chuma S, Huynh D, Sacco A, Roccaro AM, Perilla-Glen A, Noonan K, MacNabb M, Leblebjian H, Warren D, Henrick P, Castillo JJ, Richardson PG, Matous J, Weller E, Treon SP. Phase I/II trial of everolimus in combination with bortezomib and rituximab (RVR) in relapsed/refractory Waldenstrom macroglobulinemia. Leukemia. 2015 Dec;29(12):2338-46. Epub 2015 Jul 3. link to original article contains verified protocol PubMed

Investigational agents

These are drugs under study with at least some promising results for this disease.

Response criteria

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