Table 3

Summary of efficacy and toxicity for select phase 2 and 3 studies of therapeutic regimens for WM

CombinationReferenceNo. of patientsTreatment naïve (%)ORR (%)Major RR (%)CR (%)MedianSafety
TTP (mo)PFS (mo)
Rituximab + cyclophosphamide + dexamethasone 25, 26 72 100 83 74 7 35  Mild hematologic toxicity 
Rituximab + fludarabine 27 43 63 95 86 4 51  Hematologic toxicity, infection 
Rituximab + fludarabine + cyclophosphamide 28 43 65 79 74 11 NR  Hematologic toxicity, including prolonged cytopenias, infection, secondary malignancies 
Rituximab + fludarabine + cyclophosphamide 30 82 33 81 74 10  79% at 3 y; 79 in relapse Hematologic toxicity, including prolonged cytopenias, infection, secondary malignancies 
Rituximab + fludarabine + cyclophosphamide 29 40 0 80 80 10 Median not reached at 52 mo  Hematologic toxicity, including prolonged cytopenias, infection, secondary malignancies 
Rituximab + bendamustine 8 22 100 95 NA NA 69.5  Hematologic toxicity, rash, fatigue 
Rituximab + bendamustine 32 71 100 80 75 7 NR  Hematologic toxicity, rash, fatigue 
Rituximab + bortezomib 35 26 100 88 65 4 NR  IgM flare, nausea, decreased incidence of peripheral neuropathy with once-per-week bortezomib dosing 
Rituximab + bortezomib + dexamethasone 33, 34 23 100 96 83 13 66  Hematologic toxicity, high rate of peripheral neuropathy with twice-per-week bortezomib dosing 
Rituximab + bortezomib 36 37 0 81 51 5 16 15.6 IgM flare, nausea, lymphopenia 
         Low rate of peripheral neuropathy with once-per week bortezomib dosing 
Rituximab + bortezomib + dexamethasone 37 59 100 85 68 3  42 Low rate of peripheral neuropathy with twice-per-week dosing to once-per-week bortezomib dosing after first cycle, IgM flare 
Carfilzomib + rituximab + dexamethasone (I) 38 31 90 87 68 3 64% at 15 mo  IgM flare, hypogammaglobulinemia, rare cardiomyopathy 
Rituximab + lenalidomide (I) 43 16 75 50 25 0 17  Hematologic toxicity, IgM flare 
Everolimus (I) 45 60 0 73 50 0 25 21 Hematologic toxicity, stomatitis, pneumonitis, rash 
Ibrutinib 47 63 0 90.5 73 0  69% at 2 y Bleeding, atrial fibrillation, mild hematologic toxicity 
CombinationReferenceNo. of patientsTreatment naïve (%)ORR (%)Major RR (%)CR (%)MedianSafety
TTP (mo)PFS (mo)
Rituximab + cyclophosphamide + dexamethasone 25, 26 72 100 83 74 7 35  Mild hematologic toxicity 
Rituximab + fludarabine 27 43 63 95 86 4 51  Hematologic toxicity, infection 
Rituximab + fludarabine + cyclophosphamide 28 43 65 79 74 11 NR  Hematologic toxicity, including prolonged cytopenias, infection, secondary malignancies 
Rituximab + fludarabine + cyclophosphamide 30 82 33 81 74 10  79% at 3 y; 79 in relapse Hematologic toxicity, including prolonged cytopenias, infection, secondary malignancies 
Rituximab + fludarabine + cyclophosphamide 29 40 0 80 80 10 Median not reached at 52 mo  Hematologic toxicity, including prolonged cytopenias, infection, secondary malignancies 
Rituximab + bendamustine 8 22 100 95 NA NA 69.5  Hematologic toxicity, rash, fatigue 
Rituximab + bendamustine 32 71 100 80 75 7 NR  Hematologic toxicity, rash, fatigue 
Rituximab + bortezomib 35 26 100 88 65 4 NR  IgM flare, nausea, decreased incidence of peripheral neuropathy with once-per-week bortezomib dosing 
Rituximab + bortezomib + dexamethasone 33, 34 23 100 96 83 13 66  Hematologic toxicity, high rate of peripheral neuropathy with twice-per-week bortezomib dosing 
Rituximab + bortezomib 36 37 0 81 51 5 16 15.6 IgM flare, nausea, lymphopenia 
         Low rate of peripheral neuropathy with once-per week bortezomib dosing 
Rituximab + bortezomib + dexamethasone 37 59 100 85 68 3  42 Low rate of peripheral neuropathy with twice-per-week dosing to once-per-week bortezomib dosing after first cycle, IgM flare 
Carfilzomib + rituximab + dexamethasone (I) 38 31 90 87 68 3 64% at 15 mo  IgM flare, hypogammaglobulinemia, rare cardiomyopathy 
Rituximab + lenalidomide (I) 43 16 75 50 25 0 17  Hematologic toxicity, IgM flare 
Everolimus (I) 45 60 0 73 50 0 25 21 Hematologic toxicity, stomatitis, pneumonitis, rash 
Ibrutinib 47 63 0 90.5 73 0  69% at 2 y Bleeding, atrial fibrillation, mild hematologic toxicity 

I, investigational outside United States; NA, not available; NR, not reached; RR, response rate; TTP, time to progression.

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