SAFETY AND CLINICAL ACTIVITY OF TEMSIROLIMUS IN COMBINATION WITH RITUXIMAB AND DHAP IN PATIENTS WITH RELAPSED OR REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA – PRELIMINARY RESULTS OF THE STORM TRIAL
(Abstract release date: 05/19/16)
EHA Library. Witzens-Harig M. 06/09/16; 132497; E948
Disclosure(s): The trial is funded by Pfizer Inc., New York, USA. Funding includes trial organization and monitoring by the IZKS Mainz, the statistical analysis, data management and the supply of the study medication.
Prof. Dr. Mathias Witzens-Harig
Contributions
Contributions
Abstract
Abstract: E948
Type: Eposter Presentation
Background
Prognosis of diffuse large B-cell lymphoma (DLBCL) has improved with the advent of Rituximab. However, there is increasing evidence that treatment of patients with relapsed and refractory disease is challenging.
Aims
The purpose of this trial is to evaluate the safety, tolerability and efficacy of the combination of the mTOR inhibitor Temsirolimus and a standard salvage regimen (R-DHAP) in patients with relapsed or refractory DLBCL.
Methods
This is a prospective, multicenter, phase II, open-label study. Patients with relapsed or refractory DLBCL with a maximum of two prior treatment lines were eligible. The STORM regimen consisted of Rituximab 375 mg/m² (day 2) and DHAP (Dexamethasone 40mg day 3-6, Cisplatine 100 mg/m² day 3, Cytarabine 2x2 g/m² day 4) with Temsirolimus added on day 1 and 8 of a 21 d cycle, with 2-4 cycles planned. In part I, dose levels for the mTOR inhibitor Temsirolimus from 25, 50, 75 and 100 mg were predefined. Based on the observed toxicity profile, the independent data safety committee recommended a Temsirolimus dose of 25 mg given on day 1 and 8 for the part II extension cohort of the trial.
Results
In part I of this clinical trial 15 patients were included - 8 patients in the 25 mg cohort and 7 patients in the 50 mg cohort. Median age was 70 (range 49-76) years and median number of prior regimen was 1. Two DLTs (one venous thrombosis in the 25 mg cohort, one esophagus infection in the 50 mg cohort) were observed. The most frequent non-hematologic side effects were nausea (9 pts, 60%), epistaxis (7 pts, 47%), fatigue (6 pts, 40%), increased ALT (6 pts, 40%) and increased creatinine (6 pts, 40%). Frequent grade 3/4 events (n>2) in both cohorts (25mg|50mg) included leukopenia (11 pts, 73% - with a mean duration of 4.4 days | 6.7 days ), thrombocytopenia (11 pts, 73% - with a mean duration of 4.6 days | 11.9 days), lymphopenia (6pts, 40%), anemia (5 pts, 33%), neutropenia (3 pts, 20%), renal failure (3 pts, 20%) and infections (4 pts, 27%, bladder infection, esophagus infection, central venous access infection, soft tissue infection, mucositis). All but one evaluable patient responded (10/11 pts, 91%), with two CRs and one CRu (27%). Four patients could not be evaluated for response at the time of the first report. After a median follow up of 12 (range 5-22) months, no relapse had been documented (1 pt lost to follow up); since then, progression of disease has occurred in three patients and led to these patients’ death. However, only for one of these patients participation in the study ended prematurely because of progressive disease under therapy, while the other two had already dropped out due to adverse events. As far as the extension cohort of part II is concerned, preliminary data of 17 patients are reported below. Median age was 61 (range 42-74) and median number of prior regimen was one. Out of these 17 patient data sets, two could not be evaluated for response. The response rate of the remaining 15 patients was 87% (13/15 pts). Two therapy-related deaths occurred (one patient died from sepsis during neutropenia, another from cerebral bleeding, both events occurring after cycle 3). After a median follow up of 7 months for the total study population, median PFS and OS have not been reached.
Conclusion
Temsirolimus can be safely added to DHAP and Rituximab with promising activity. This conclusion drawn from part I of the study has been confirmed by the preliminary data of part II. Recruitment of the part II of the trial is continuing.
Session topic: E-poster
Keyword(s): Diffuse large B cell lymphoma, MTOR, Salvage chemotherapy
Type: Eposter Presentation
Background
Prognosis of diffuse large B-cell lymphoma (DLBCL) has improved with the advent of Rituximab. However, there is increasing evidence that treatment of patients with relapsed and refractory disease is challenging.
Aims
The purpose of this trial is to evaluate the safety, tolerability and efficacy of the combination of the mTOR inhibitor Temsirolimus and a standard salvage regimen (R-DHAP) in patients with relapsed or refractory DLBCL.
Methods
This is a prospective, multicenter, phase II, open-label study. Patients with relapsed or refractory DLBCL with a maximum of two prior treatment lines were eligible. The STORM regimen consisted of Rituximab 375 mg/m² (day 2) and DHAP (Dexamethasone 40mg day 3-6, Cisplatine 100 mg/m² day 3, Cytarabine 2x2 g/m² day 4) with Temsirolimus added on day 1 and 8 of a 21 d cycle, with 2-4 cycles planned. In part I, dose levels for the mTOR inhibitor Temsirolimus from 25, 50, 75 and 100 mg were predefined. Based on the observed toxicity profile, the independent data safety committee recommended a Temsirolimus dose of 25 mg given on day 1 and 8 for the part II extension cohort of the trial.
Results
In part I of this clinical trial 15 patients were included - 8 patients in the 25 mg cohort and 7 patients in the 50 mg cohort. Median age was 70 (range 49-76) years and median number of prior regimen was 1. Two DLTs (one venous thrombosis in the 25 mg cohort, one esophagus infection in the 50 mg cohort) were observed. The most frequent non-hematologic side effects were nausea (9 pts, 60%), epistaxis (7 pts, 47%), fatigue (6 pts, 40%), increased ALT (6 pts, 40%) and increased creatinine (6 pts, 40%). Frequent grade 3/4 events (n>2) in both cohorts (25mg|50mg) included leukopenia (11 pts, 73% - with a mean duration of 4.4 days | 6.7 days ), thrombocytopenia (11 pts, 73% - with a mean duration of 4.6 days | 11.9 days), lymphopenia (6pts, 40%), anemia (5 pts, 33%), neutropenia (3 pts, 20%), renal failure (3 pts, 20%) and infections (4 pts, 27%, bladder infection, esophagus infection, central venous access infection, soft tissue infection, mucositis). All but one evaluable patient responded (10/11 pts, 91%), with two CRs and one CRu (27%). Four patients could not be evaluated for response at the time of the first report. After a median follow up of 12 (range 5-22) months, no relapse had been documented (1 pt lost to follow up); since then, progression of disease has occurred in three patients and led to these patients’ death. However, only for one of these patients participation in the study ended prematurely because of progressive disease under therapy, while the other two had already dropped out due to adverse events. As far as the extension cohort of part II is concerned, preliminary data of 17 patients are reported below. Median age was 61 (range 42-74) and median number of prior regimen was one. Out of these 17 patient data sets, two could not be evaluated for response. The response rate of the remaining 15 patients was 87% (13/15 pts). Two therapy-related deaths occurred (one patient died from sepsis during neutropenia, another from cerebral bleeding, both events occurring after cycle 3). After a median follow up of 7 months for the total study population, median PFS and OS have not been reached.
Conclusion
Temsirolimus can be safely added to DHAP and Rituximab with promising activity. This conclusion drawn from part I of the study has been confirmed by the preliminary data of part II. Recruitment of the part II of the trial is continuing.
Session topic: E-poster
Keyword(s): Diffuse large B cell lymphoma, MTOR, Salvage chemotherapy
Abstract: E948
Type: Eposter Presentation
Background
Prognosis of diffuse large B-cell lymphoma (DLBCL) has improved with the advent of Rituximab. However, there is increasing evidence that treatment of patients with relapsed and refractory disease is challenging.
Aims
The purpose of this trial is to evaluate the safety, tolerability and efficacy of the combination of the mTOR inhibitor Temsirolimus and a standard salvage regimen (R-DHAP) in patients with relapsed or refractory DLBCL.
Methods
This is a prospective, multicenter, phase II, open-label study. Patients with relapsed or refractory DLBCL with a maximum of two prior treatment lines were eligible. The STORM regimen consisted of Rituximab 375 mg/m² (day 2) and DHAP (Dexamethasone 40mg day 3-6, Cisplatine 100 mg/m² day 3, Cytarabine 2x2 g/m² day 4) with Temsirolimus added on day 1 and 8 of a 21 d cycle, with 2-4 cycles planned. In part I, dose levels for the mTOR inhibitor Temsirolimus from 25, 50, 75 and 100 mg were predefined. Based on the observed toxicity profile, the independent data safety committee recommended a Temsirolimus dose of 25 mg given on day 1 and 8 for the part II extension cohort of the trial.
Results
In part I of this clinical trial 15 patients were included - 8 patients in the 25 mg cohort and 7 patients in the 50 mg cohort. Median age was 70 (range 49-76) years and median number of prior regimen was 1. Two DLTs (one venous thrombosis in the 25 mg cohort, one esophagus infection in the 50 mg cohort) were observed. The most frequent non-hematologic side effects were nausea (9 pts, 60%), epistaxis (7 pts, 47%), fatigue (6 pts, 40%), increased ALT (6 pts, 40%) and increased creatinine (6 pts, 40%). Frequent grade 3/4 events (n>2) in both cohorts (25mg|50mg) included leukopenia (11 pts, 73% - with a mean duration of 4.4 days | 6.7 days ), thrombocytopenia (11 pts, 73% - with a mean duration of 4.6 days | 11.9 days), lymphopenia (6pts, 40%), anemia (5 pts, 33%), neutropenia (3 pts, 20%), renal failure (3 pts, 20%) and infections (4 pts, 27%, bladder infection, esophagus infection, central venous access infection, soft tissue infection, mucositis). All but one evaluable patient responded (10/11 pts, 91%), with two CRs and one CRu (27%). Four patients could not be evaluated for response at the time of the first report. After a median follow up of 12 (range 5-22) months, no relapse had been documented (1 pt lost to follow up); since then, progression of disease has occurred in three patients and led to these patients’ death. However, only for one of these patients participation in the study ended prematurely because of progressive disease under therapy, while the other two had already dropped out due to adverse events. As far as the extension cohort of part II is concerned, preliminary data of 17 patients are reported below. Median age was 61 (range 42-74) and median number of prior regimen was one. Out of these 17 patient data sets, two could not be evaluated for response. The response rate of the remaining 15 patients was 87% (13/15 pts). Two therapy-related deaths occurred (one patient died from sepsis during neutropenia, another from cerebral bleeding, both events occurring after cycle 3). After a median follow up of 7 months for the total study population, median PFS and OS have not been reached.
Conclusion
Temsirolimus can be safely added to DHAP and Rituximab with promising activity. This conclusion drawn from part I of the study has been confirmed by the preliminary data of part II. Recruitment of the part II of the trial is continuing.
Session topic: E-poster
Keyword(s): Diffuse large B cell lymphoma, MTOR, Salvage chemotherapy
Type: Eposter Presentation
Background
Prognosis of diffuse large B-cell lymphoma (DLBCL) has improved with the advent of Rituximab. However, there is increasing evidence that treatment of patients with relapsed and refractory disease is challenging.
Aims
The purpose of this trial is to evaluate the safety, tolerability and efficacy of the combination of the mTOR inhibitor Temsirolimus and a standard salvage regimen (R-DHAP) in patients with relapsed or refractory DLBCL.
Methods
This is a prospective, multicenter, phase II, open-label study. Patients with relapsed or refractory DLBCL with a maximum of two prior treatment lines were eligible. The STORM regimen consisted of Rituximab 375 mg/m² (day 2) and DHAP (Dexamethasone 40mg day 3-6, Cisplatine 100 mg/m² day 3, Cytarabine 2x2 g/m² day 4) with Temsirolimus added on day 1 and 8 of a 21 d cycle, with 2-4 cycles planned. In part I, dose levels for the mTOR inhibitor Temsirolimus from 25, 50, 75 and 100 mg were predefined. Based on the observed toxicity profile, the independent data safety committee recommended a Temsirolimus dose of 25 mg given on day 1 and 8 for the part II extension cohort of the trial.
Results
In part I of this clinical trial 15 patients were included - 8 patients in the 25 mg cohort and 7 patients in the 50 mg cohort. Median age was 70 (range 49-76) years and median number of prior regimen was 1. Two DLTs (one venous thrombosis in the 25 mg cohort, one esophagus infection in the 50 mg cohort) were observed. The most frequent non-hematologic side effects were nausea (9 pts, 60%), epistaxis (7 pts, 47%), fatigue (6 pts, 40%), increased ALT (6 pts, 40%) and increased creatinine (6 pts, 40%). Frequent grade 3/4 events (n>2) in both cohorts (25mg|50mg) included leukopenia (11 pts, 73% - with a mean duration of 4.4 days | 6.7 days ), thrombocytopenia (11 pts, 73% - with a mean duration of 4.6 days | 11.9 days), lymphopenia (6pts, 40%), anemia (5 pts, 33%), neutropenia (3 pts, 20%), renal failure (3 pts, 20%) and infections (4 pts, 27%, bladder infection, esophagus infection, central venous access infection, soft tissue infection, mucositis). All but one evaluable patient responded (10/11 pts, 91%), with two CRs and one CRu (27%). Four patients could not be evaluated for response at the time of the first report. After a median follow up of 12 (range 5-22) months, no relapse had been documented (1 pt lost to follow up); since then, progression of disease has occurred in three patients and led to these patients’ death. However, only for one of these patients participation in the study ended prematurely because of progressive disease under therapy, while the other two had already dropped out due to adverse events. As far as the extension cohort of part II is concerned, preliminary data of 17 patients are reported below. Median age was 61 (range 42-74) and median number of prior regimen was one. Out of these 17 patient data sets, two could not be evaluated for response. The response rate of the remaining 15 patients was 87% (13/15 pts). Two therapy-related deaths occurred (one patient died from sepsis during neutropenia, another from cerebral bleeding, both events occurring after cycle 3). After a median follow up of 7 months for the total study population, median PFS and OS have not been reached.
Conclusion
Temsirolimus can be safely added to DHAP and Rituximab with promising activity. This conclusion drawn from part I of the study has been confirmed by the preliminary data of part II. Recruitment of the part II of the trial is continuing.
Session topic: E-poster
Keyword(s): Diffuse large B cell lymphoma, MTOR, Salvage chemotherapy
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