SUCCESSFUL BL-8040 TREATMENT FOR RELAPSED AML PATIENTS ? SINGLE CENTER EXPERIENCE
(Abstract release date: 05/19/16)
EHA Library. Rowe J. 06/09/16; 134564; PB1664
Prof. Dr. Jacob Rowe
Contributions
Contributions
Abstract
Abstract: PB1664
Type: Publication Only
Background
BL-8040 is a high-affinity antagonist of CXCR4, a chemokine receptor that is directly involved in tumor progression, angiogenesis, metastasis, and cell survival. BL-8040 binds to CXCR4 on leukemic cells, inhibiting its function, thus releasing them from the protective microenvironment of the bone marrow (BM) resulting in amplification of their sensitivity to chemotherapy. BL-8040 also has a direct anti-tumor effect by selectively inducing apoptosis of malignant cells.
Aims
To assess the effectiveness of BL-8040 in combination with cytarabine (Ara-C) in three patients with relapsed AML who were treated under compassionate protocol.
Methods
Treatment of relapsed AML patients with SC BL-8040 1.25mg/kg on days 1-7 together with Ara-C 1.5 gr/m2 from day 3-7.
Results
Case 1: A 75 year old male with relapsed AML, 7 years after initial diagnosis. At the time of diagnosis he had normal karyotype and treated successfully with 7+3 followed by consolidation with Ara-C. At time of relapse he presented with dysplastic changes and additional chromosome 13 karyotype. At relapse the patient was treated with Ara-C and BL-8040. On day 35 his BM was in complete remission (CR) with less than 5% blasts. Maintenance therapy with azacitidine began three months later. Nine months post induction the patient is still in CR.Case 2: A 23 year old male with a history of Hodgkin lymphoma at age 17. At the age of 20 he was diagnosed with AML with the t(8;21) chromosomal abnormality. He was treated with 7+3 followed by consolidation with Ara-C. A year later he relapsed and received an allogeneic transplant (allo-HSCT). Two years post-transplant the patient relapsed with intra and extramedullary disease represented by a large chest wall mass. He was treated with BL-8040 and Ara-C as a salvage treatment. There was some resolution of the extramedullary mass on the first 2 days of monotherapy treatment with BL-8040 (before the onset of Ara-C). The patient experienced severe injection site pain and generalized muscle pain which required narcotics for analgesia. The patient entered CR on day 34 and underwent a second allo-HSCT. Almost a year and half post BL-8040 salvage treatment the patient is still in CR.Case 3: A 66 years old female with relapsed AML, 14 months after first diagnosis. At the time of diagnosis she presented with a complex karyotype. She received induction treatment followed by allo-HSCT but relapsed 3 months later. She was then treated with Ara-C and donor lymphocyte infusion (DLI) reaching CR; 7 months later she relapsed again. A second salvage treatment with BL-8040 and Ara-C was provided. During treatment she suffered from severe muscle pain (chest and legs). The patient didn’t reach response showing 52% myeloblasts on day 24 BM examination. Two days later the patient died. The direct cause of her death is likely to be disease related.
Conclusion
Three patients were treated with BL-8040 and Ara-C as salvage therapy for relapsed AML. The safety profile was similar and the adverse events were well managed. These were characterized by injection site reactions and severe muscle pain. BL-8040 in combination with Ara-C can be administered safely to relapsed, heavily pretreated, AML patients. BL-8040 in combination with Ara-C has been shown to be an effective regimen for bone marrow as well as extramedullary AML. BL-8040 in combination with Ara-C should be considered as a bridging therapy for allo-HSCT.
Session topic: E-poster
Type: Publication Only
Background
BL-8040 is a high-affinity antagonist of CXCR4, a chemokine receptor that is directly involved in tumor progression, angiogenesis, metastasis, and cell survival. BL-8040 binds to CXCR4 on leukemic cells, inhibiting its function, thus releasing them from the protective microenvironment of the bone marrow (BM) resulting in amplification of their sensitivity to chemotherapy. BL-8040 also has a direct anti-tumor effect by selectively inducing apoptosis of malignant cells.
Aims
To assess the effectiveness of BL-8040 in combination with cytarabine (Ara-C) in three patients with relapsed AML who were treated under compassionate protocol.
Methods
Treatment of relapsed AML patients with SC BL-8040 1.25mg/kg on days 1-7 together with Ara-C 1.5 gr/m2 from day 3-7.
Results
Case 1: A 75 year old male with relapsed AML, 7 years after initial diagnosis. At the time of diagnosis he had normal karyotype and treated successfully with 7+3 followed by consolidation with Ara-C. At time of relapse he presented with dysplastic changes and additional chromosome 13 karyotype. At relapse the patient was treated with Ara-C and BL-8040. On day 35 his BM was in complete remission (CR) with less than 5% blasts. Maintenance therapy with azacitidine began three months later. Nine months post induction the patient is still in CR.Case 2: A 23 year old male with a history of Hodgkin lymphoma at age 17. At the age of 20 he was diagnosed with AML with the t(8;21) chromosomal abnormality. He was treated with 7+3 followed by consolidation with Ara-C. A year later he relapsed and received an allogeneic transplant (allo-HSCT). Two years post-transplant the patient relapsed with intra and extramedullary disease represented by a large chest wall mass. He was treated with BL-8040 and Ara-C as a salvage treatment. There was some resolution of the extramedullary mass on the first 2 days of monotherapy treatment with BL-8040 (before the onset of Ara-C). The patient experienced severe injection site pain and generalized muscle pain which required narcotics for analgesia. The patient entered CR on day 34 and underwent a second allo-HSCT. Almost a year and half post BL-8040 salvage treatment the patient is still in CR.Case 3: A 66 years old female with relapsed AML, 14 months after first diagnosis. At the time of diagnosis she presented with a complex karyotype. She received induction treatment followed by allo-HSCT but relapsed 3 months later. She was then treated with Ara-C and donor lymphocyte infusion (DLI) reaching CR; 7 months later she relapsed again. A second salvage treatment with BL-8040 and Ara-C was provided. During treatment she suffered from severe muscle pain (chest and legs). The patient didn’t reach response showing 52% myeloblasts on day 24 BM examination. Two days later the patient died. The direct cause of her death is likely to be disease related.
Conclusion
Three patients were treated with BL-8040 and Ara-C as salvage therapy for relapsed AML. The safety profile was similar and the adverse events were well managed. These were characterized by injection site reactions and severe muscle pain. BL-8040 in combination with Ara-C can be administered safely to relapsed, heavily pretreated, AML patients. BL-8040 in combination with Ara-C has been shown to be an effective regimen for bone marrow as well as extramedullary AML. BL-8040 in combination with Ara-C should be considered as a bridging therapy for allo-HSCT.
Session topic: E-poster
Abstract: PB1664
Type: Publication Only
Background
BL-8040 is a high-affinity antagonist of CXCR4, a chemokine receptor that is directly involved in tumor progression, angiogenesis, metastasis, and cell survival. BL-8040 binds to CXCR4 on leukemic cells, inhibiting its function, thus releasing them from the protective microenvironment of the bone marrow (BM) resulting in amplification of their sensitivity to chemotherapy. BL-8040 also has a direct anti-tumor effect by selectively inducing apoptosis of malignant cells.
Aims
To assess the effectiveness of BL-8040 in combination with cytarabine (Ara-C) in three patients with relapsed AML who were treated under compassionate protocol.
Methods
Treatment of relapsed AML patients with SC BL-8040 1.25mg/kg on days 1-7 together with Ara-C 1.5 gr/m2 from day 3-7.
Results
Case 1: A 75 year old male with relapsed AML, 7 years after initial diagnosis. At the time of diagnosis he had normal karyotype and treated successfully with 7+3 followed by consolidation with Ara-C. At time of relapse he presented with dysplastic changes and additional chromosome 13 karyotype. At relapse the patient was treated with Ara-C and BL-8040. On day 35 his BM was in complete remission (CR) with less than 5% blasts. Maintenance therapy with azacitidine began three months later. Nine months post induction the patient is still in CR.Case 2: A 23 year old male with a history of Hodgkin lymphoma at age 17. At the age of 20 he was diagnosed with AML with the t(8;21) chromosomal abnormality. He was treated with 7+3 followed by consolidation with Ara-C. A year later he relapsed and received an allogeneic transplant (allo-HSCT). Two years post-transplant the patient relapsed with intra and extramedullary disease represented by a large chest wall mass. He was treated with BL-8040 and Ara-C as a salvage treatment. There was some resolution of the extramedullary mass on the first 2 days of monotherapy treatment with BL-8040 (before the onset of Ara-C). The patient experienced severe injection site pain and generalized muscle pain which required narcotics for analgesia. The patient entered CR on day 34 and underwent a second allo-HSCT. Almost a year and half post BL-8040 salvage treatment the patient is still in CR.Case 3: A 66 years old female with relapsed AML, 14 months after first diagnosis. At the time of diagnosis she presented with a complex karyotype. She received induction treatment followed by allo-HSCT but relapsed 3 months later. She was then treated with Ara-C and donor lymphocyte infusion (DLI) reaching CR; 7 months later she relapsed again. A second salvage treatment with BL-8040 and Ara-C was provided. During treatment she suffered from severe muscle pain (chest and legs). The patient didn’t reach response showing 52% myeloblasts on day 24 BM examination. Two days later the patient died. The direct cause of her death is likely to be disease related.
Conclusion
Three patients were treated with BL-8040 and Ara-C as salvage therapy for relapsed AML. The safety profile was similar and the adverse events were well managed. These were characterized by injection site reactions and severe muscle pain. BL-8040 in combination with Ara-C can be administered safely to relapsed, heavily pretreated, AML patients. BL-8040 in combination with Ara-C has been shown to be an effective regimen for bone marrow as well as extramedullary AML. BL-8040 in combination with Ara-C should be considered as a bridging therapy for allo-HSCT.
Session topic: E-poster
Type: Publication Only
Background
BL-8040 is a high-affinity antagonist of CXCR4, a chemokine receptor that is directly involved in tumor progression, angiogenesis, metastasis, and cell survival. BL-8040 binds to CXCR4 on leukemic cells, inhibiting its function, thus releasing them from the protective microenvironment of the bone marrow (BM) resulting in amplification of their sensitivity to chemotherapy. BL-8040 also has a direct anti-tumor effect by selectively inducing apoptosis of malignant cells.
Aims
To assess the effectiveness of BL-8040 in combination with cytarabine (Ara-C) in three patients with relapsed AML who were treated under compassionate protocol.
Methods
Treatment of relapsed AML patients with SC BL-8040 1.25mg/kg on days 1-7 together with Ara-C 1.5 gr/m2 from day 3-7.
Results
Case 1: A 75 year old male with relapsed AML, 7 years after initial diagnosis. At the time of diagnosis he had normal karyotype and treated successfully with 7+3 followed by consolidation with Ara-C. At time of relapse he presented with dysplastic changes and additional chromosome 13 karyotype. At relapse the patient was treated with Ara-C and BL-8040. On day 35 his BM was in complete remission (CR) with less than 5% blasts. Maintenance therapy with azacitidine began three months later. Nine months post induction the patient is still in CR.Case 2: A 23 year old male with a history of Hodgkin lymphoma at age 17. At the age of 20 he was diagnosed with AML with the t(8;21) chromosomal abnormality. He was treated with 7+3 followed by consolidation with Ara-C. A year later he relapsed and received an allogeneic transplant (allo-HSCT). Two years post-transplant the patient relapsed with intra and extramedullary disease represented by a large chest wall mass. He was treated with BL-8040 and Ara-C as a salvage treatment. There was some resolution of the extramedullary mass on the first 2 days of monotherapy treatment with BL-8040 (before the onset of Ara-C). The patient experienced severe injection site pain and generalized muscle pain which required narcotics for analgesia. The patient entered CR on day 34 and underwent a second allo-HSCT. Almost a year and half post BL-8040 salvage treatment the patient is still in CR.Case 3: A 66 years old female with relapsed AML, 14 months after first diagnosis. At the time of diagnosis she presented with a complex karyotype. She received induction treatment followed by allo-HSCT but relapsed 3 months later. She was then treated with Ara-C and donor lymphocyte infusion (DLI) reaching CR; 7 months later she relapsed again. A second salvage treatment with BL-8040 and Ara-C was provided. During treatment she suffered from severe muscle pain (chest and legs). The patient didn’t reach response showing 52% myeloblasts on day 24 BM examination. Two days later the patient died. The direct cause of her death is likely to be disease related.
Conclusion
Three patients were treated with BL-8040 and Ara-C as salvage therapy for relapsed AML. The safety profile was similar and the adverse events were well managed. These were characterized by injection site reactions and severe muscle pain. BL-8040 in combination with Ara-C can be administered safely to relapsed, heavily pretreated, AML patients. BL-8040 in combination with Ara-C has been shown to be an effective regimen for bone marrow as well as extramedullary AML. BL-8040 in combination with Ara-C should be considered as a bridging therapy for allo-HSCT.
Session topic: E-poster
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