A PHASE II STUDY OF THE COMBINATION OF OFATUMUMAB WITH FLUDARABINE AND CYCLOPHOSPHAMIDE IN PATIENTS WITH RELAPSED OR REFRACTORY WALDENSTRÖM’S MACROGLOBULINEMIA
(Abstract release date: 05/19/16)
EHA Library. Kastritis E. 06/09/16; 132704; E1155
Dr. Efstathios Kastritis
Contributions
Contributions
Abstract
Abstract: E1155
Type: Eposter Presentation
Background
Ofatumumab is a novel anti-CD20 monoclonal antibody which has been approved for the treatment of chronic lymphocytic leukemia, but limited data exist for patients with Waldenström’s macroglobulinemia (WM). Ofatumumab targets CD20 in a different epitope than rituximab and may also have a more favorable profile regarding infusion related reactions since, in contrast to rituximab, it is a human and not chimeric antibody. Fludarabine with cyclophosphamide (FC) is a very effective treatment when combined with rituximab (FCR) in patients with relapsed or refractory WM.
Aims
to evaluate the combination of ofatumumab with FC (OFC) in symptomatic patients with relapsed or refractory WM requiring therapy
Methods
This is a phase 2 single center trial. Treatment consisted of four cycles of the OFC combination. A single dose of 100 mg of ofatumumab was given I.V. on day 1 of the first cycle followed by 1000 mg on day 8. Fludarabine 25 mg/m2 and cyclophosphamide 250 mg/m2 were given intravenously for 3 consecutive days every 28 days for 4 cycles, followed by ofatumumab (1000 mg) in cycles 2 to 4. Primary end point was overall response rate (complete (CR) + very good (VGPR) + partial (PR) + minor (MR) response) and secondary endpoints included safety and toxicity, occurrence of “IgM flare”, duration of response, progression free and overall survival
Results
From 2013 until 2014, twelve patients were treated with OFC; 75% and 17% were high and intermediate risk per the International Prognostic Scoring System for WM. All patients had previously been exposed to rituximab and 4 (33%) were refractory to the last course of rituximab, while 4 (33%) had previously received bortezomib. On intent to treat, 11/12 (92%) patients responded (17% VGPR, 67% PR and 8% MR). Median time to first response (≥MR) was 2.2 months and median time to ≥PR was 8.5 months. In 11 (92%) patients a continuing decrease of IgM levels has been observed and at 6 months post OFC completion 6 (50%) patients have improved their response from MR to PR or VGPR. “IgM flare” was not observed. All patients completed the planned 4 cycles of treatment. Infusion related reactions occurred in only one patient (grade 2) who had a history of severe rituximab intolerance, during the day 8 dosing (1000 mg); the patient completed the full schedule without further reactions. After a median follow-up of 23 months, -- patients have progressed or died and the median progression-free survival is 21 months. The 2-year duration of response for patients with ≥PR is 70%, and 2-year survival is 83%. Neutropenia grade 3 occurred in 67% and grade 4 in 25% of patients. One patient experienced neutropenic fever and the dose of FC was reduced according to the protocol.
Conclusion
OFC is a rapidly acting combination, inducing high response rates, including deep and durable responses in heavily pretreated WM patients, even in those refractory to rituximab and/or bortezomib. Ofatumumab is well tolerated with low incidence of infusion related reactions, and although the combination has myelotoxicity, it is manageable.
Session topic: E-poster
Keyword(s): CD20, Phase II, Waldenstrom's macroglobulinemia
Type: Eposter Presentation
Background
Ofatumumab is a novel anti-CD20 monoclonal antibody which has been approved for the treatment of chronic lymphocytic leukemia, but limited data exist for patients with Waldenström’s macroglobulinemia (WM). Ofatumumab targets CD20 in a different epitope than rituximab and may also have a more favorable profile regarding infusion related reactions since, in contrast to rituximab, it is a human and not chimeric antibody. Fludarabine with cyclophosphamide (FC) is a very effective treatment when combined with rituximab (FCR) in patients with relapsed or refractory WM.
Aims
to evaluate the combination of ofatumumab with FC (OFC) in symptomatic patients with relapsed or refractory WM requiring therapy
Methods
This is a phase 2 single center trial. Treatment consisted of four cycles of the OFC combination. A single dose of 100 mg of ofatumumab was given I.V. on day 1 of the first cycle followed by 1000 mg on day 8. Fludarabine 25 mg/m2 and cyclophosphamide 250 mg/m2 were given intravenously for 3 consecutive days every 28 days for 4 cycles, followed by ofatumumab (1000 mg) in cycles 2 to 4. Primary end point was overall response rate (complete (CR) + very good (VGPR) + partial (PR) + minor (MR) response) and secondary endpoints included safety and toxicity, occurrence of “IgM flare”, duration of response, progression free and overall survival
Results
From 2013 until 2014, twelve patients were treated with OFC; 75% and 17% were high and intermediate risk per the International Prognostic Scoring System for WM. All patients had previously been exposed to rituximab and 4 (33%) were refractory to the last course of rituximab, while 4 (33%) had previously received bortezomib. On intent to treat, 11/12 (92%) patients responded (17% VGPR, 67% PR and 8% MR). Median time to first response (≥MR) was 2.2 months and median time to ≥PR was 8.5 months. In 11 (92%) patients a continuing decrease of IgM levels has been observed and at 6 months post OFC completion 6 (50%) patients have improved their response from MR to PR or VGPR. “IgM flare” was not observed. All patients completed the planned 4 cycles of treatment. Infusion related reactions occurred in only one patient (grade 2) who had a history of severe rituximab intolerance, during the day 8 dosing (1000 mg); the patient completed the full schedule without further reactions. After a median follow-up of 23 months, -- patients have progressed or died and the median progression-free survival is 21 months. The 2-year duration of response for patients with ≥PR is 70%, and 2-year survival is 83%. Neutropenia grade 3 occurred in 67% and grade 4 in 25% of patients. One patient experienced neutropenic fever and the dose of FC was reduced according to the protocol.
Conclusion
OFC is a rapidly acting combination, inducing high response rates, including deep and durable responses in heavily pretreated WM patients, even in those refractory to rituximab and/or bortezomib. Ofatumumab is well tolerated with low incidence of infusion related reactions, and although the combination has myelotoxicity, it is manageable.
Session topic: E-poster
Keyword(s): CD20, Phase II, Waldenstrom's macroglobulinemia
Abstract: E1155
Type: Eposter Presentation
Background
Ofatumumab is a novel anti-CD20 monoclonal antibody which has been approved for the treatment of chronic lymphocytic leukemia, but limited data exist for patients with Waldenström’s macroglobulinemia (WM). Ofatumumab targets CD20 in a different epitope than rituximab and may also have a more favorable profile regarding infusion related reactions since, in contrast to rituximab, it is a human and not chimeric antibody. Fludarabine with cyclophosphamide (FC) is a very effective treatment when combined with rituximab (FCR) in patients with relapsed or refractory WM.
Aims
to evaluate the combination of ofatumumab with FC (OFC) in symptomatic patients with relapsed or refractory WM requiring therapy
Methods
This is a phase 2 single center trial. Treatment consisted of four cycles of the OFC combination. A single dose of 100 mg of ofatumumab was given I.V. on day 1 of the first cycle followed by 1000 mg on day 8. Fludarabine 25 mg/m2 and cyclophosphamide 250 mg/m2 were given intravenously for 3 consecutive days every 28 days for 4 cycles, followed by ofatumumab (1000 mg) in cycles 2 to 4. Primary end point was overall response rate (complete (CR) + very good (VGPR) + partial (PR) + minor (MR) response) and secondary endpoints included safety and toxicity, occurrence of “IgM flare”, duration of response, progression free and overall survival
Results
From 2013 until 2014, twelve patients were treated with OFC; 75% and 17% were high and intermediate risk per the International Prognostic Scoring System for WM. All patients had previously been exposed to rituximab and 4 (33%) were refractory to the last course of rituximab, while 4 (33%) had previously received bortezomib. On intent to treat, 11/12 (92%) patients responded (17% VGPR, 67% PR and 8% MR). Median time to first response (≥MR) was 2.2 months and median time to ≥PR was 8.5 months. In 11 (92%) patients a continuing decrease of IgM levels has been observed and at 6 months post OFC completion 6 (50%) patients have improved their response from MR to PR or VGPR. “IgM flare” was not observed. All patients completed the planned 4 cycles of treatment. Infusion related reactions occurred in only one patient (grade 2) who had a history of severe rituximab intolerance, during the day 8 dosing (1000 mg); the patient completed the full schedule without further reactions. After a median follow-up of 23 months, -- patients have progressed or died and the median progression-free survival is 21 months. The 2-year duration of response for patients with ≥PR is 70%, and 2-year survival is 83%. Neutropenia grade 3 occurred in 67% and grade 4 in 25% of patients. One patient experienced neutropenic fever and the dose of FC was reduced according to the protocol.
Conclusion
OFC is a rapidly acting combination, inducing high response rates, including deep and durable responses in heavily pretreated WM patients, even in those refractory to rituximab and/or bortezomib. Ofatumumab is well tolerated with low incidence of infusion related reactions, and although the combination has myelotoxicity, it is manageable.
Session topic: E-poster
Keyword(s): CD20, Phase II, Waldenstrom's macroglobulinemia
Type: Eposter Presentation
Background
Ofatumumab is a novel anti-CD20 monoclonal antibody which has been approved for the treatment of chronic lymphocytic leukemia, but limited data exist for patients with Waldenström’s macroglobulinemia (WM). Ofatumumab targets CD20 in a different epitope than rituximab and may also have a more favorable profile regarding infusion related reactions since, in contrast to rituximab, it is a human and not chimeric antibody. Fludarabine with cyclophosphamide (FC) is a very effective treatment when combined with rituximab (FCR) in patients with relapsed or refractory WM.
Aims
to evaluate the combination of ofatumumab with FC (OFC) in symptomatic patients with relapsed or refractory WM requiring therapy
Methods
This is a phase 2 single center trial. Treatment consisted of four cycles of the OFC combination. A single dose of 100 mg of ofatumumab was given I.V. on day 1 of the first cycle followed by 1000 mg on day 8. Fludarabine 25 mg/m2 and cyclophosphamide 250 mg/m2 were given intravenously for 3 consecutive days every 28 days for 4 cycles, followed by ofatumumab (1000 mg) in cycles 2 to 4. Primary end point was overall response rate (complete (CR) + very good (VGPR) + partial (PR) + minor (MR) response) and secondary endpoints included safety and toxicity, occurrence of “IgM flare”, duration of response, progression free and overall survival
Results
From 2013 until 2014, twelve patients were treated with OFC; 75% and 17% were high and intermediate risk per the International Prognostic Scoring System for WM. All patients had previously been exposed to rituximab and 4 (33%) were refractory to the last course of rituximab, while 4 (33%) had previously received bortezomib. On intent to treat, 11/12 (92%) patients responded (17% VGPR, 67% PR and 8% MR). Median time to first response (≥MR) was 2.2 months and median time to ≥PR was 8.5 months. In 11 (92%) patients a continuing decrease of IgM levels has been observed and at 6 months post OFC completion 6 (50%) patients have improved their response from MR to PR or VGPR. “IgM flare” was not observed. All patients completed the planned 4 cycles of treatment. Infusion related reactions occurred in only one patient (grade 2) who had a history of severe rituximab intolerance, during the day 8 dosing (1000 mg); the patient completed the full schedule without further reactions. After a median follow-up of 23 months, -- patients have progressed or died and the median progression-free survival is 21 months. The 2-year duration of response for patients with ≥PR is 70%, and 2-year survival is 83%. Neutropenia grade 3 occurred in 67% and grade 4 in 25% of patients. One patient experienced neutropenic fever and the dose of FC was reduced according to the protocol.
Conclusion
OFC is a rapidly acting combination, inducing high response rates, including deep and durable responses in heavily pretreated WM patients, even in those refractory to rituximab and/or bortezomib. Ofatumumab is well tolerated with low incidence of infusion related reactions, and although the combination has myelotoxicity, it is manageable.
Session topic: E-poster
Keyword(s): CD20, Phase II, Waldenstrom's macroglobulinemia
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