SUBGROUP ANALYSES OF DIFFUSE LARGE B-CELL LYMPHOMA AND INDOLENT LYMPHOMA COHORTS FROM A PHASE IIA STUDY OF SINGLE-AGENT MOR208 IN PATIENTS WITH RELAPSED OR REFRACTORY NON-HODGKIN'S LYMPHOMA
(Abstract release date: 05/19/16)
EHA Library. Jurczak W. 06/12/16; 135283; S789
Prof. Dr. Wojciech Jurczak
Contributions
Contributions
Abstract
Abstract: S789
Type: Oral Presentation
Presentation during EHA21: On Sunday, June 12, 2016 from 08:15 - 08:30
Location: Hall A1
Background
There is a high unmet medical need for new efficacious and tolerable regimens for patients with relapsed or refractory (R-R) non-Hodgkin’s lymphoma (NHL). CD19 is expressed by most B-cell NHLs; in contrast to other targets, CD19 expression is maintained at a stable level during the course of the disease. MOR208, an Fc-engineered, humanized monoclonal CD19 antibody demonstrates activity in certain leukemia and lymphoma model systems through enhanced antigen-dependent cell-mediated cytotoxicity and antigen-dependent cell-mediated phagocytosis. A phase I study showed MOR208 to be safe and well-tolerated with encouraging single-agent activity in patients with chronic lymphocytic leukemia. Therefore MOR208 may have clinical use as a new therapeutic agent in this setting.
Aims
This analysis focused on the preliminary efficacy and safety of MOR208 in diffuse large B-cell lymphoma (DLBCL) and indolent (i) NHL cohorts. The primary endpoint was investigator assessed overall response rate (ORR).
Methods
This is an open-label, multicenter, phase IIa study of MOR208 in R-R NHL patients progressing after at least one prior rituximab-containing therapy. Patients were enrolled into 4 cohorts of aggressive (DLBCL and mantle cell lymphoma) and iNHLs (follicular lymphoma and other iNHLs). Patients received single-agent MOR208, 12 mg/kg IV, weekly, for 8 weeks (2 cycles); treatment could continue for 4 additional weeks in patients with at least stable disease after 2 cycles. MOR208 maintenance could be given (every 2 or 4 weeks) until progression in patients with complete (CR) or partial response (PR) at 12 weeks.
Results
In total, 92 patients were enrolled including 35 (38%) with DLBCL and 45 (49%) with iNHL. ORR was 26% in DLBCL (9/35 patients; 2 CRs and 7 PRs), and 27% in iNHL (12/45 patients; 5 CRs and 7 PRs). In evaluable patients (those who completed at least 2 cycles and had a response assessment) the ORR was 36% in DLBCL (25 evaluable patients), and 30% in iNHL (40 evaluable patients), respectively. Median duration of response was 13.7 months for DLBCL patients (1.2–26, 3 ongoing and >20 months in remission) and 8.4 months for iNHL patients (2.5–20.3, 6 ongoing, including 1 patient >20.3 months in remission). In DLBCL responders, 5/9 were rituximab-refractory (either no response or response lasting <6 months to a previous rituximab-containing therapy), of which 2 patients had a response duration of >19.8 months and 1 patient of >1 year under MOR208 treatment. The incidence of grade ≥3 hematologic treatment emergent adverse events was low (DLBCL: 9/35, 26%; iNHL: 4/45, 9%), including neutropenia, anemia and thrombocytopenia in 14%, 9% and 6% of DLBCL patients and 4%, 0% and 0% of iNHL patients. Infusion-related reactions were seen in 3/35 (9%) and 4/45 (9%) patients in the DLBCL and iNHL cohorts, all of grade 1–2 except for one grade 4 dyspnea. There were no treatment-related deaths and no trend towards late toxicity
Conclusion
Single-agent MOR208 was associated with a promising ORR including CRs and long-lasting responses in both DLBCL and iNHL, including in patients with rituximab-refractory disease. These efficacy data, and the excellent safety and tolerability profile of MOR208 further justify the development of MOR208 as part of a combination therapy in B-cell malignancies.
Session topic: Aggressive lymphoma with emphasis on novel agents
Keyword(s): CD19, Diffuse large B cell lymphoma, Monoclonal antibody, NHL
Type: Oral Presentation
Presentation during EHA21: On Sunday, June 12, 2016 from 08:15 - 08:30
Location: Hall A1
Background
There is a high unmet medical need for new efficacious and tolerable regimens for patients with relapsed or refractory (R-R) non-Hodgkin’s lymphoma (NHL). CD19 is expressed by most B-cell NHLs; in contrast to other targets, CD19 expression is maintained at a stable level during the course of the disease. MOR208, an Fc-engineered, humanized monoclonal CD19 antibody demonstrates activity in certain leukemia and lymphoma model systems through enhanced antigen-dependent cell-mediated cytotoxicity and antigen-dependent cell-mediated phagocytosis. A phase I study showed MOR208 to be safe and well-tolerated with encouraging single-agent activity in patients with chronic lymphocytic leukemia. Therefore MOR208 may have clinical use as a new therapeutic agent in this setting.
Aims
This analysis focused on the preliminary efficacy and safety of MOR208 in diffuse large B-cell lymphoma (DLBCL) and indolent (i) NHL cohorts. The primary endpoint was investigator assessed overall response rate (ORR).
Methods
This is an open-label, multicenter, phase IIa study of MOR208 in R-R NHL patients progressing after at least one prior rituximab-containing therapy. Patients were enrolled into 4 cohorts of aggressive (DLBCL and mantle cell lymphoma) and iNHLs (follicular lymphoma and other iNHLs). Patients received single-agent MOR208, 12 mg/kg IV, weekly, for 8 weeks (2 cycles); treatment could continue for 4 additional weeks in patients with at least stable disease after 2 cycles. MOR208 maintenance could be given (every 2 or 4 weeks) until progression in patients with complete (CR) or partial response (PR) at 12 weeks.
Results
In total, 92 patients were enrolled including 35 (38%) with DLBCL and 45 (49%) with iNHL. ORR was 26% in DLBCL (9/35 patients; 2 CRs and 7 PRs), and 27% in iNHL (12/45 patients; 5 CRs and 7 PRs). In evaluable patients (those who completed at least 2 cycles and had a response assessment) the ORR was 36% in DLBCL (25 evaluable patients), and 30% in iNHL (40 evaluable patients), respectively. Median duration of response was 13.7 months for DLBCL patients (1.2–26, 3 ongoing and >20 months in remission) and 8.4 months for iNHL patients (2.5–20.3, 6 ongoing, including 1 patient >20.3 months in remission). In DLBCL responders, 5/9 were rituximab-refractory (either no response or response lasting <6 months to a previous rituximab-containing therapy), of which 2 patients had a response duration of >19.8 months and 1 patient of >1 year under MOR208 treatment. The incidence of grade ≥3 hematologic treatment emergent adverse events was low (DLBCL: 9/35, 26%; iNHL: 4/45, 9%), including neutropenia, anemia and thrombocytopenia in 14%, 9% and 6% of DLBCL patients and 4%, 0% and 0% of iNHL patients. Infusion-related reactions were seen in 3/35 (9%) and 4/45 (9%) patients in the DLBCL and iNHL cohorts, all of grade 1–2 except for one grade 4 dyspnea. There were no treatment-related deaths and no trend towards late toxicity
Conclusion
Single-agent MOR208 was associated with a promising ORR including CRs and long-lasting responses in both DLBCL and iNHL, including in patients with rituximab-refractory disease. These efficacy data, and the excellent safety and tolerability profile of MOR208 further justify the development of MOR208 as part of a combination therapy in B-cell malignancies.
Session topic: Aggressive lymphoma with emphasis on novel agents
Keyword(s): CD19, Diffuse large B cell lymphoma, Monoclonal antibody, NHL
Abstract: S789
Type: Oral Presentation
Presentation during EHA21: On Sunday, June 12, 2016 from 08:15 - 08:30
Location: Hall A1
Background
There is a high unmet medical need for new efficacious and tolerable regimens for patients with relapsed or refractory (R-R) non-Hodgkin’s lymphoma (NHL). CD19 is expressed by most B-cell NHLs; in contrast to other targets, CD19 expression is maintained at a stable level during the course of the disease. MOR208, an Fc-engineered, humanized monoclonal CD19 antibody demonstrates activity in certain leukemia and lymphoma model systems through enhanced antigen-dependent cell-mediated cytotoxicity and antigen-dependent cell-mediated phagocytosis. A phase I study showed MOR208 to be safe and well-tolerated with encouraging single-agent activity in patients with chronic lymphocytic leukemia. Therefore MOR208 may have clinical use as a new therapeutic agent in this setting.
Aims
This analysis focused on the preliminary efficacy and safety of MOR208 in diffuse large B-cell lymphoma (DLBCL) and indolent (i) NHL cohorts. The primary endpoint was investigator assessed overall response rate (ORR).
Methods
This is an open-label, multicenter, phase IIa study of MOR208 in R-R NHL patients progressing after at least one prior rituximab-containing therapy. Patients were enrolled into 4 cohorts of aggressive (DLBCL and mantle cell lymphoma) and iNHLs (follicular lymphoma and other iNHLs). Patients received single-agent MOR208, 12 mg/kg IV, weekly, for 8 weeks (2 cycles); treatment could continue for 4 additional weeks in patients with at least stable disease after 2 cycles. MOR208 maintenance could be given (every 2 or 4 weeks) until progression in patients with complete (CR) or partial response (PR) at 12 weeks.
Results
In total, 92 patients were enrolled including 35 (38%) with DLBCL and 45 (49%) with iNHL. ORR was 26% in DLBCL (9/35 patients; 2 CRs and 7 PRs), and 27% in iNHL (12/45 patients; 5 CRs and 7 PRs). In evaluable patients (those who completed at least 2 cycles and had a response assessment) the ORR was 36% in DLBCL (25 evaluable patients), and 30% in iNHL (40 evaluable patients), respectively. Median duration of response was 13.7 months for DLBCL patients (1.2–26, 3 ongoing and >20 months in remission) and 8.4 months for iNHL patients (2.5–20.3, 6 ongoing, including 1 patient >20.3 months in remission). In DLBCL responders, 5/9 were rituximab-refractory (either no response or response lasting <6 months to a previous rituximab-containing therapy), of which 2 patients had a response duration of >19.8 months and 1 patient of >1 year under MOR208 treatment. The incidence of grade ≥3 hematologic treatment emergent adverse events was low (DLBCL: 9/35, 26%; iNHL: 4/45, 9%), including neutropenia, anemia and thrombocytopenia in 14%, 9% and 6% of DLBCL patients and 4%, 0% and 0% of iNHL patients. Infusion-related reactions were seen in 3/35 (9%) and 4/45 (9%) patients in the DLBCL and iNHL cohorts, all of grade 1–2 except for one grade 4 dyspnea. There were no treatment-related deaths and no trend towards late toxicity
Conclusion
Single-agent MOR208 was associated with a promising ORR including CRs and long-lasting responses in both DLBCL and iNHL, including in patients with rituximab-refractory disease. These efficacy data, and the excellent safety and tolerability profile of MOR208 further justify the development of MOR208 as part of a combination therapy in B-cell malignancies.
Session topic: Aggressive lymphoma with emphasis on novel agents
Keyword(s): CD19, Diffuse large B cell lymphoma, Monoclonal antibody, NHL
Type: Oral Presentation
Presentation during EHA21: On Sunday, June 12, 2016 from 08:15 - 08:30
Location: Hall A1
Background
There is a high unmet medical need for new efficacious and tolerable regimens for patients with relapsed or refractory (R-R) non-Hodgkin’s lymphoma (NHL). CD19 is expressed by most B-cell NHLs; in contrast to other targets, CD19 expression is maintained at a stable level during the course of the disease. MOR208, an Fc-engineered, humanized monoclonal CD19 antibody demonstrates activity in certain leukemia and lymphoma model systems through enhanced antigen-dependent cell-mediated cytotoxicity and antigen-dependent cell-mediated phagocytosis. A phase I study showed MOR208 to be safe and well-tolerated with encouraging single-agent activity in patients with chronic lymphocytic leukemia. Therefore MOR208 may have clinical use as a new therapeutic agent in this setting.
Aims
This analysis focused on the preliminary efficacy and safety of MOR208 in diffuse large B-cell lymphoma (DLBCL) and indolent (i) NHL cohorts. The primary endpoint was investigator assessed overall response rate (ORR).
Methods
This is an open-label, multicenter, phase IIa study of MOR208 in R-R NHL patients progressing after at least one prior rituximab-containing therapy. Patients were enrolled into 4 cohorts of aggressive (DLBCL and mantle cell lymphoma) and iNHLs (follicular lymphoma and other iNHLs). Patients received single-agent MOR208, 12 mg/kg IV, weekly, for 8 weeks (2 cycles); treatment could continue for 4 additional weeks in patients with at least stable disease after 2 cycles. MOR208 maintenance could be given (every 2 or 4 weeks) until progression in patients with complete (CR) or partial response (PR) at 12 weeks.
Results
In total, 92 patients were enrolled including 35 (38%) with DLBCL and 45 (49%) with iNHL. ORR was 26% in DLBCL (9/35 patients; 2 CRs and 7 PRs), and 27% in iNHL (12/45 patients; 5 CRs and 7 PRs). In evaluable patients (those who completed at least 2 cycles and had a response assessment) the ORR was 36% in DLBCL (25 evaluable patients), and 30% in iNHL (40 evaluable patients), respectively. Median duration of response was 13.7 months for DLBCL patients (1.2–26, 3 ongoing and >20 months in remission) and 8.4 months for iNHL patients (2.5–20.3, 6 ongoing, including 1 patient >20.3 months in remission). In DLBCL responders, 5/9 were rituximab-refractory (either no response or response lasting <6 months to a previous rituximab-containing therapy), of which 2 patients had a response duration of >19.8 months and 1 patient of >1 year under MOR208 treatment. The incidence of grade ≥3 hematologic treatment emergent adverse events was low (DLBCL: 9/35, 26%; iNHL: 4/45, 9%), including neutropenia, anemia and thrombocytopenia in 14%, 9% and 6% of DLBCL patients and 4%, 0% and 0% of iNHL patients. Infusion-related reactions were seen in 3/35 (9%) and 4/45 (9%) patients in the DLBCL and iNHL cohorts, all of grade 1–2 except for one grade 4 dyspnea. There were no treatment-related deaths and no trend towards late toxicity
Conclusion
Single-agent MOR208 was associated with a promising ORR including CRs and long-lasting responses in both DLBCL and iNHL, including in patients with rituximab-refractory disease. These efficacy data, and the excellent safety and tolerability profile of MOR208 further justify the development of MOR208 as part of a combination therapy in B-cell malignancies.
Session topic: Aggressive lymphoma with emphasis on novel agents
Keyword(s): CD19, Diffuse large B cell lymphoma, Monoclonal antibody, NHL
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