PHASE 1B STUDY OF PEMBROLIZUMAB IN PATIENTS WITH RELAPSED/REFRACTORY PRIMARY MEDIASTINAL LARGE B-CELL LYMPHOMA: KEYNOTE-013
(Abstract release date: 05/19/16)
EHA Library. Zinzani P. 06/12/16; 135291; S797
Prof. Dr. Pier Luigi Zinzani
Contributions
Contributions
Abstract
Abstract: S797
Type: Oral Presentation
Presentation during EHA21: On Sunday, June 12, 2016 from 09:00 - 09:15
Location: Hall A2
Background
Primary mediastinal large B-cell lymphoma (PMBCL) frequently exhibits 9p24.1 alterations, leading to overexpression of the PD-1 ligands, PD-L1 and PD-L2. This provides a possible mechanism of immune evasion and suggests that PMBCL could have a genetically determined vulnerability to PD-1 blockade. Pembrolizumab is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands. Pembrolizumab has already demonstrated robust antitumor activity in advanced solid tumors and in classical Hodgkin lymphoma. KEYNOTE-013 (NCT01953692) is a multicenter, multicohort phase 1b study designed to evaluate the safety and preliminary efficacy of pembrolizumab in patients with hematologic malignancies. Preliminary results of the PMBCL cohort of KEYNOTE-013 are reported.
Aims
To determine the safety, tolerability, and antitumor activity of pembrolizumab in patients with relapsed/refractory (R/R) PMBCL.
Methods
Patients with R/R disease who have relapsed after or are ineligible for autologous stem cell transplantation (ASCT) received pembrolizumab IV 10 mg/kg Q2W or 200 mg Q3W for up to 2 years or until confirmed disease progression or unacceptable toxicity. Primary end points were safety and ORR. Response was evaluated using computed tomography (CT) and positron emission tomography (PET) at weeks 6 and 12, and every 8 weeks thereafter, using IHP 2007 criteria. Other end points included complete remission rate and duration of response (DOR). Informed consent was obtained for all patients.
Results
As of February 1, 2016, 16 patients were enrolled and treated in this cohort. The first 11 patients received pembrolizumab 10 mg/kg every 2 weeks; the next 5 patients received a fixed dose of 200 mg every 3 weeks, which has demonstrated equivalence based on PK/PD studies. Median age was 30 years (range, 22-62), 44% had ≥4 prior lines of therapy, 31% had prior ASCT, and 75% had prior radiation. 10 patients (62%) experienced treatment-related AEs, most commonly grade 1-2 decreased appetite, diarrhea, fatigue, hypothyroidism, nausea, and pyrexia (2 patients each). Only 1 patient experienced a grade 3 treatment-related AE (neutropenia), and there were no grade 4 treatment-related AEs or treatment-related deaths. 4 patients experienced serious AEs, including grade 3 pneumonia in 3 patients and grade 3 cough in 1 patient; all were unrelated to study drug. No patients discontinued for toxicity.Among the 16 treated patients, the median follow-up was 5.0 months (range, 0.8-22 months) and the objective response rate (ORR) was 37.5% (6/16), with 1 patient (6.25%) achieving a complete remission and 5 patients (31.25%) achieving a partial response. One subject discontinued treatment based on clinical progression before the first assessment and was considered a non-responder. The median DOR has not been reached (range, 0.03+-17+ months), with 5 responses ongoing at the time of data cutoff. 9 have discontinued treatment: 5 because of progressive disease based on imaging, 3 because of clinical progressive disease, and 1 because of physician decision.
Conclusion
The preliminary results of KEYNOTE-013 indicate that PD-1 blockade with pembrolizumab is associated with a tolerable safety profile and a promising response rate in heavily pretreated patients with R/R PMBCL. These patients often have a very poor outcome with conventional therapy, justifying further studies of pembrolizumab in this population.
Session topic: Relapsed Hodgkin Lymphoma & Primary Mediastinal Large B-Cell Lymphoma (PM-DLBCL)
Type: Oral Presentation
Presentation during EHA21: On Sunday, June 12, 2016 from 09:00 - 09:15
Location: Hall A2
Background
Primary mediastinal large B-cell lymphoma (PMBCL) frequently exhibits 9p24.1 alterations, leading to overexpression of the PD-1 ligands, PD-L1 and PD-L2. This provides a possible mechanism of immune evasion and suggests that PMBCL could have a genetically determined vulnerability to PD-1 blockade. Pembrolizumab is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands. Pembrolizumab has already demonstrated robust antitumor activity in advanced solid tumors and in classical Hodgkin lymphoma. KEYNOTE-013 (NCT01953692) is a multicenter, multicohort phase 1b study designed to evaluate the safety and preliminary efficacy of pembrolizumab in patients with hematologic malignancies. Preliminary results of the PMBCL cohort of KEYNOTE-013 are reported.
Aims
To determine the safety, tolerability, and antitumor activity of pembrolizumab in patients with relapsed/refractory (R/R) PMBCL.
Methods
Patients with R/R disease who have relapsed after or are ineligible for autologous stem cell transplantation (ASCT) received pembrolizumab IV 10 mg/kg Q2W or 200 mg Q3W for up to 2 years or until confirmed disease progression or unacceptable toxicity. Primary end points were safety and ORR. Response was evaluated using computed tomography (CT) and positron emission tomography (PET) at weeks 6 and 12, and every 8 weeks thereafter, using IHP 2007 criteria. Other end points included complete remission rate and duration of response (DOR). Informed consent was obtained for all patients.
Results
As of February 1, 2016, 16 patients were enrolled and treated in this cohort. The first 11 patients received pembrolizumab 10 mg/kg every 2 weeks; the next 5 patients received a fixed dose of 200 mg every 3 weeks, which has demonstrated equivalence based on PK/PD studies. Median age was 30 years (range, 22-62), 44% had ≥4 prior lines of therapy, 31% had prior ASCT, and 75% had prior radiation. 10 patients (62%) experienced treatment-related AEs, most commonly grade 1-2 decreased appetite, diarrhea, fatigue, hypothyroidism, nausea, and pyrexia (2 patients each). Only 1 patient experienced a grade 3 treatment-related AE (neutropenia), and there were no grade 4 treatment-related AEs or treatment-related deaths. 4 patients experienced serious AEs, including grade 3 pneumonia in 3 patients and grade 3 cough in 1 patient; all were unrelated to study drug. No patients discontinued for toxicity.Among the 16 treated patients, the median follow-up was 5.0 months (range, 0.8-22 months) and the objective response rate (ORR) was 37.5% (6/16), with 1 patient (6.25%) achieving a complete remission and 5 patients (31.25%) achieving a partial response. One subject discontinued treatment based on clinical progression before the first assessment and was considered a non-responder. The median DOR has not been reached (range, 0.03+-17+ months), with 5 responses ongoing at the time of data cutoff. 9 have discontinued treatment: 5 because of progressive disease based on imaging, 3 because of clinical progressive disease, and 1 because of physician decision.
Conclusion
The preliminary results of KEYNOTE-013 indicate that PD-1 blockade with pembrolizumab is associated with a tolerable safety profile and a promising response rate in heavily pretreated patients with R/R PMBCL. These patients often have a very poor outcome with conventional therapy, justifying further studies of pembrolizumab in this population.
Session topic: Relapsed Hodgkin Lymphoma & Primary Mediastinal Large B-Cell Lymphoma (PM-DLBCL)
Abstract: S797
Type: Oral Presentation
Presentation during EHA21: On Sunday, June 12, 2016 from 09:00 - 09:15
Location: Hall A2
Background
Primary mediastinal large B-cell lymphoma (PMBCL) frequently exhibits 9p24.1 alterations, leading to overexpression of the PD-1 ligands, PD-L1 and PD-L2. This provides a possible mechanism of immune evasion and suggests that PMBCL could have a genetically determined vulnerability to PD-1 blockade. Pembrolizumab is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands. Pembrolizumab has already demonstrated robust antitumor activity in advanced solid tumors and in classical Hodgkin lymphoma. KEYNOTE-013 (NCT01953692) is a multicenter, multicohort phase 1b study designed to evaluate the safety and preliminary efficacy of pembrolizumab in patients with hematologic malignancies. Preliminary results of the PMBCL cohort of KEYNOTE-013 are reported.
Aims
To determine the safety, tolerability, and antitumor activity of pembrolizumab in patients with relapsed/refractory (R/R) PMBCL.
Methods
Patients with R/R disease who have relapsed after or are ineligible for autologous stem cell transplantation (ASCT) received pembrolizumab IV 10 mg/kg Q2W or 200 mg Q3W for up to 2 years or until confirmed disease progression or unacceptable toxicity. Primary end points were safety and ORR. Response was evaluated using computed tomography (CT) and positron emission tomography (PET) at weeks 6 and 12, and every 8 weeks thereafter, using IHP 2007 criteria. Other end points included complete remission rate and duration of response (DOR). Informed consent was obtained for all patients.
Results
As of February 1, 2016, 16 patients were enrolled and treated in this cohort. The first 11 patients received pembrolizumab 10 mg/kg every 2 weeks; the next 5 patients received a fixed dose of 200 mg every 3 weeks, which has demonstrated equivalence based on PK/PD studies. Median age was 30 years (range, 22-62), 44% had ≥4 prior lines of therapy, 31% had prior ASCT, and 75% had prior radiation. 10 patients (62%) experienced treatment-related AEs, most commonly grade 1-2 decreased appetite, diarrhea, fatigue, hypothyroidism, nausea, and pyrexia (2 patients each). Only 1 patient experienced a grade 3 treatment-related AE (neutropenia), and there were no grade 4 treatment-related AEs or treatment-related deaths. 4 patients experienced serious AEs, including grade 3 pneumonia in 3 patients and grade 3 cough in 1 patient; all were unrelated to study drug. No patients discontinued for toxicity.Among the 16 treated patients, the median follow-up was 5.0 months (range, 0.8-22 months) and the objective response rate (ORR) was 37.5% (6/16), with 1 patient (6.25%) achieving a complete remission and 5 patients (31.25%) achieving a partial response. One subject discontinued treatment based on clinical progression before the first assessment and was considered a non-responder. The median DOR has not been reached (range, 0.03+-17+ months), with 5 responses ongoing at the time of data cutoff. 9 have discontinued treatment: 5 because of progressive disease based on imaging, 3 because of clinical progressive disease, and 1 because of physician decision.
Conclusion
The preliminary results of KEYNOTE-013 indicate that PD-1 blockade with pembrolizumab is associated with a tolerable safety profile and a promising response rate in heavily pretreated patients with R/R PMBCL. These patients often have a very poor outcome with conventional therapy, justifying further studies of pembrolizumab in this population.
Session topic: Relapsed Hodgkin Lymphoma & Primary Mediastinal Large B-Cell Lymphoma (PM-DLBCL)
Type: Oral Presentation
Presentation during EHA21: On Sunday, June 12, 2016 from 09:00 - 09:15
Location: Hall A2
Background
Primary mediastinal large B-cell lymphoma (PMBCL) frequently exhibits 9p24.1 alterations, leading to overexpression of the PD-1 ligands, PD-L1 and PD-L2. This provides a possible mechanism of immune evasion and suggests that PMBCL could have a genetically determined vulnerability to PD-1 blockade. Pembrolizumab is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands. Pembrolizumab has already demonstrated robust antitumor activity in advanced solid tumors and in classical Hodgkin lymphoma. KEYNOTE-013 (NCT01953692) is a multicenter, multicohort phase 1b study designed to evaluate the safety and preliminary efficacy of pembrolizumab in patients with hematologic malignancies. Preliminary results of the PMBCL cohort of KEYNOTE-013 are reported.
Aims
To determine the safety, tolerability, and antitumor activity of pembrolizumab in patients with relapsed/refractory (R/R) PMBCL.
Methods
Patients with R/R disease who have relapsed after or are ineligible for autologous stem cell transplantation (ASCT) received pembrolizumab IV 10 mg/kg Q2W or 200 mg Q3W for up to 2 years or until confirmed disease progression or unacceptable toxicity. Primary end points were safety and ORR. Response was evaluated using computed tomography (CT) and positron emission tomography (PET) at weeks 6 and 12, and every 8 weeks thereafter, using IHP 2007 criteria. Other end points included complete remission rate and duration of response (DOR). Informed consent was obtained for all patients.
Results
As of February 1, 2016, 16 patients were enrolled and treated in this cohort. The first 11 patients received pembrolizumab 10 mg/kg every 2 weeks; the next 5 patients received a fixed dose of 200 mg every 3 weeks, which has demonstrated equivalence based on PK/PD studies. Median age was 30 years (range, 22-62), 44% had ≥4 prior lines of therapy, 31% had prior ASCT, and 75% had prior radiation. 10 patients (62%) experienced treatment-related AEs, most commonly grade 1-2 decreased appetite, diarrhea, fatigue, hypothyroidism, nausea, and pyrexia (2 patients each). Only 1 patient experienced a grade 3 treatment-related AE (neutropenia), and there were no grade 4 treatment-related AEs or treatment-related deaths. 4 patients experienced serious AEs, including grade 3 pneumonia in 3 patients and grade 3 cough in 1 patient; all were unrelated to study drug. No patients discontinued for toxicity.Among the 16 treated patients, the median follow-up was 5.0 months (range, 0.8-22 months) and the objective response rate (ORR) was 37.5% (6/16), with 1 patient (6.25%) achieving a complete remission and 5 patients (31.25%) achieving a partial response. One subject discontinued treatment based on clinical progression before the first assessment and was considered a non-responder. The median DOR has not been reached (range, 0.03+-17+ months), with 5 responses ongoing at the time of data cutoff. 9 have discontinued treatment: 5 because of progressive disease based on imaging, 3 because of clinical progressive disease, and 1 because of physician decision.
Conclusion
The preliminary results of KEYNOTE-013 indicate that PD-1 blockade with pembrolizumab is associated with a tolerable safety profile and a promising response rate in heavily pretreated patients with R/R PMBCL. These patients often have a very poor outcome with conventional therapy, justifying further studies of pembrolizumab in this population.
Session topic: Relapsed Hodgkin Lymphoma & Primary Mediastinal Large B-Cell Lymphoma (PM-DLBCL)
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