Answer
Bulky symptomatic disease is characterized by one or more of the following:
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Bulky adenopathy
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Symptomatic hepatosplenomegaly
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Cytopenias
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Hyperviscosity
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Constitutional symptoms
See Table 1, below, for common regimens that have been used and outcome data. Bendamustine/rituximab is the preferred initial therapy for most patients, while ibrutinib/rituximab is an acceptable alternative for elderly patients who cannot tolerate chemotherapy. [4] Bortezomib should be avoided in patients with baseline neuropathy. Nucleoside analogs such as fludarabine or cladribine pose a risk of stem cell damage and leukemogenesis and should not be used as initial therapy in patients who are candidates for stem cell transplantation (SCT). [5]
Table 1. Common regimens used to treat bulky symptomatic Waldenstrom macroglobulinemia (Open Table in a new window)
Regimen |
Dose/Schedule |
Study Results |
BR |
Bendamustine 90 mg/m2 IV days 1-2 Rituximab 375 mg/m2 IV day 1 Repeat 28-day cycle for 4-6 cycles |
Rummel et al [6] : 41 treatment-naive patients; ORR 95% |
DRC |
Dexamethasone 20 mg IV day 1 Rituximab 375 mg/m2 IV day 1 Cyclophosphamide 100 mg/m2 PO BID days 1-5 Repeat 21-day cycle for 6 cycles |
Kastritis et al [7] : 72 treatment-naive patients; ORR 83%, CRR 7% |
BDR |
Bortezomib 1.3 mg/m2 IV days 1, 4, 8, 11 during cycle 1 followed by 1.6 mg/m2 on days 1, 7, 15, and 22 for cycles 2-5 Dexamethasone 40 mg IV weekly starting day 1 of cycle 2 Rituximab 375 mg/m2 IV weekly starting day 1 of cycle 2 5 cycles total; 21 days for cycle 1; 35 days for cycles 2-5 |
Gavriatopoulou et al [8] : 59 treatment-naive patients; ORR 85%, CRR 3% |
Rituximab |
Rituximab 375 mg/m2 IV once weekly x 4 weeks |
Gertz et al [9] : 69 treatment-naive and previously treated patients; ORR 27.5%, CRR 0% |
Ibrutinib |
Ibrutinib 420 mg PO once daily until disease progression |
Treon et al [10] : 30 treatment-naive patients; ORR 100%, CRR 0% Treon et al [11] : 63 previously treated patients; ORR 90.5% |
Ibrutinib/rituximab |
Ibrutinib 420 mg PO once daily until disease progression Rituximab 375 mg/m2 IV once weekly during weeks 1-4 and weeks 17-20 |
Dimopoulos et al [12] : 150 treatment-naive and previously treated patients; ORR 92%, CRR 3% |
Acalabrutinib |
Acalabrutinib 100 mg PO BID until disease progression |
Owen et al [13] : 106 treatment-naive and previously treated patients; ORR 93%, CRR 0% |
Cladribine/rituximab |
Cladribine 0.1 mg/kg SC days 1-5 Rituximab 375 mg/m2 IV day 1 Repeat 28-day cycle for 4 cycles |
Laszlo et al [14] : 29 treatment-naive and previously treated patients; ORR 90%, CRR 24% |
Fludarabine/rituximab |
Fludarabine 25 mg/m2 IV days 1-5 Rituximab 375 mg/m2 IV day 1 Repeat 28-day cycle for 4-6 cycles |
Peinert et al [15] : 27 treatment-naive and previously treated patients; ORR 90%, CRR 3% |
FCR |
Fludarabine 25 mg/m2 IV days 1-3 Cyclophosphamide 250 mg/m2 IV days 1-3 Rituximab 375 mg/m2 IV day 1 Primary: Repeat 28-day cycle for 4-6 cycles May also be given with mitoxantrone 10 mg/m2 on day 1 |
Tedeschi et al [16] : 43 treatment-naive and previously treated patients; ORR 79%, CRR 11.6% |
ORR = overall response rate; CRR = complete response rate |
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Tables
Regimen |
Dose/Schedule |
Study Results |
BR |
Bendamustine 90 mg/m2 IV days 1-2 Rituximab 375 mg/m2 IV day 1 Repeat 28-day cycle for 4-6 cycles |
Rummel et al [6] : 41 treatment-naive patients; ORR 95% |
DRC |
Dexamethasone 20 mg IV day 1 Rituximab 375 mg/m2 IV day 1 Cyclophosphamide 100 mg/m2 PO BID days 1-5 Repeat 21-day cycle for 6 cycles |
Kastritis et al [7] : 72 treatment-naive patients; ORR 83%, CRR 7% |
BDR |
Bortezomib 1.3 mg/m2 IV days 1, 4, 8, 11 during cycle 1 followed by 1.6 mg/m2 on days 1, 7, 15, and 22 for cycles 2-5 Dexamethasone 40 mg IV weekly starting day 1 of cycle 2 Rituximab 375 mg/m2 IV weekly starting day 1 of cycle 2 5 cycles total; 21 days for cycle 1; 35 days for cycles 2-5 |
Gavriatopoulou et al [8] : 59 treatment-naive patients; ORR 85%, CRR 3% |
Rituximab |
Rituximab 375 mg/m2 IV once weekly x 4 weeks |
Gertz et al [9] : 69 treatment-naive and previously treated patients; ORR 27.5%, CRR 0% |
Ibrutinib |
Ibrutinib 420 mg PO once daily until disease progression |
Treon et al [10] : 30 treatment-naive patients; ORR 100%, CRR 0% Treon et al [11] : 63 previously treated patients; ORR 90.5% |
Ibrutinib/rituximab |
Ibrutinib 420 mg PO once daily until disease progression Rituximab 375 mg/m2 IV once weekly during weeks 1-4 and weeks 17-20 |
Dimopoulos et al [12] : 150 treatment-naive and previously treated patients; ORR 92%, CRR 3% |
Acalabrutinib |
Acalabrutinib 100 mg PO BID until disease progression |
Owen et al [13] : 106 treatment-naive and previously treated patients; ORR 93%, CRR 0% |
Cladribine/rituximab |
Cladribine 0.1 mg/kg SC days 1-5 Rituximab 375 mg/m2 IV day 1 Repeat 28-day cycle for 4 cycles |
Laszlo et al [14] : 29 treatment-naive and previously treated patients; ORR 90%, CRR 24% |
Fludarabine/rituximab |
Fludarabine 25 mg/m2 IV days 1-5 Rituximab 375 mg/m2 IV day 1 Repeat 28-day cycle for 4-6 cycles |
Peinert et al [15] : 27 treatment-naive and previously treated patients; ORR 90%, CRR 3% |
FCR |
Fludarabine 25 mg/m2 IV days 1-3 Cyclophosphamide 250 mg/m2 IV days 1-3 Rituximab 375 mg/m2 IV day 1 Primary: Repeat 28-day cycle for 4-6 cycles May also be given with mitoxantrone 10 mg/m2 on day 1 |
Tedeschi et al [16] : 43 treatment-naive and previously treated patients; ORR 79%, CRR 11.6% |
ORR = overall response rate; CRR = complete response rate |
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