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For HIV-positive patients with Burkitt lymphoma, a modified intensive chemotherapy regimen produced overall and progression-free survival rates comparable with those seen in HIV-free patients with Burkitt, with manageable toxicities, reported researchers in a multicenter clinical trial.
The AIDS Malignancy Consortium (AMC) 048 study looked at the use of a modified version of the dose intensive CODOX-M/IVAC regimen, consisting of cyclophosphamide, vincristine, doxorubicin, high-dose methotrexate/ifosfamide, etoposide, and high-dose cytarabine. Compared with the standard regimen, the investigators added rituximab, reduced and/or rescheduled cyclophosphamide and methotrexate, limited the use of vincristine, and used combination intrathecal chemotherapy to prevent central nervous system involvement.
The study included 34 HIV-positive patients (30 men and 4 women) with Burkitt, 26 of whom were also receiving highly active antiretroviral therapy (HAART). The patients ranged in age from 19-55 (median 42) years. Of the 34 patients, 25 had Ann Arbor stage IV disease, 2 had stage III, 1 had stage IIE, 2 had stage II, and 4 had stage I. Median age was 42 years (range, 19-55 years).
The median CD4 count was 195 cells/mL; five patients had fewer than 100 cells/mL
Progression-free survival at 1 year was 69%, and 1- and 2-year overall survival were 72% and 69%, respectively.
The modified CODOX-M/IVAC regimen was associated with a grade 3 to 4 toxicity rate of 79%, with no grade 3 or 4 mucositis reported. In contrast, virtually all patients who receive the unmodified regimen develop at least one grade 3 or greater toxicity.
In total, there were 20 hematologic, 14 infectious, and 6 metabolic toxicities. Five patients did not complete treatment because of adverse events.
There were 11 deaths, including 1 treatment-related death of a patient with encephalopathy, hepatic failure, hepatitis B, and pneumonia cited as contributing causes. Of the remaining 10 patients, 8 died from systemic disease progression, and 2 died during follow-up, 1 during remission from a fungal infection and 1 from nonmalignant complications of HIV.
The investigators say that the addition of rituximab may have contributed to the favorable outcomes, and that rescheduling and limiting the amount of high-dose methotrexate delivered likely contributed to lower incidences of both severe mucositis and neutropenic fever.
Although a separate trial is evaluating a different regimen (EPOCH-R; etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab) in Burkitt lymphoma, “the modified AMC 048 version of CODOX-M/IVAC-R may better serve patients who present with CNS disease or are at high risk for CNS relapse (e.g., patients with bone marrow, testicular, or multiple extranodal sites), because it contains high-dose cytarabine and methotrexate, drugs that cross the blood-brain barrier. Consequently, AMC048 represents a reasonable treatment option in the appropriate setting, possibly irrespective of HIV status.”
The study by Dr. Ariela Noy from the Memorial Sloan Kettering Cancer Center in New York and her colleagues, is published in Blood.
Although the results of AMC 048 are encouraging and demonstrate that intensive regimens for AIDS-related Burkitt lymphoma are both tolerable and efficacious, the question of whether multiagent dose intense regimens are needed remains unanswered. Using a short course of EPOCH (infusional etoposide, oral prednisone, infusional vincristine, bolus cyclophosphamide, and infusional doxorubicin) with a double dose of rituximab (SC-EPOCH-RR) to treat 11 patients with AIDS-related Burkitt lymphoma, researchers at the National Cancer Institute have observed progression-free survival of 100% and overall survival of 90% at a median follow-up of 73 months. This regimen omits systemic ifosfamide and high-dose methotrexate. Although both agents are thought to be important for disease control in Burkitt lymphoma, especially to treat and/or prevent lymphomatous CNS involvement, they also have substantial toxicities. In the NCI study, only 1 patient had CNS involvement at baseline and was successfully treated with intrathecal methotrexate alone. No patient relapsed in the CNS. However, given the small number of patients enrolled in this single institution study, there remains significant concern that omission of these agents will jeopardize disease control, specifically in high-risk patients. It will be interesting to see whether the results of the NCI study will be maintained in the ongoing larger cooperative group trial that currently evaluates dose-adjusted EPOCH-R.
Dr. Stefan K. Barta is with the Fox Chase Cancer Center/Temple University Health System in Philadelphia. He made his remarks in an editorial that accompanied the study.
Although the results of AMC 048 are encouraging and demonstrate that intensive regimens for AIDS-related Burkitt lymphoma are both tolerable and efficacious, the question of whether multiagent dose intense regimens are needed remains unanswered. Using a short course of EPOCH (infusional etoposide, oral prednisone, infusional vincristine, bolus cyclophosphamide, and infusional doxorubicin) with a double dose of rituximab (SC-EPOCH-RR) to treat 11 patients with AIDS-related Burkitt lymphoma, researchers at the National Cancer Institute have observed progression-free survival of 100% and overall survival of 90% at a median follow-up of 73 months. This regimen omits systemic ifosfamide and high-dose methotrexate. Although both agents are thought to be important for disease control in Burkitt lymphoma, especially to treat and/or prevent lymphomatous CNS involvement, they also have substantial toxicities. In the NCI study, only 1 patient had CNS involvement at baseline and was successfully treated with intrathecal methotrexate alone. No patient relapsed in the CNS. However, given the small number of patients enrolled in this single institution study, there remains significant concern that omission of these agents will jeopardize disease control, specifically in high-risk patients. It will be interesting to see whether the results of the NCI study will be maintained in the ongoing larger cooperative group trial that currently evaluates dose-adjusted EPOCH-R.
Dr. Stefan K. Barta is with the Fox Chase Cancer Center/Temple University Health System in Philadelphia. He made his remarks in an editorial that accompanied the study.
Although the results of AMC 048 are encouraging and demonstrate that intensive regimens for AIDS-related Burkitt lymphoma are both tolerable and efficacious, the question of whether multiagent dose intense regimens are needed remains unanswered. Using a short course of EPOCH (infusional etoposide, oral prednisone, infusional vincristine, bolus cyclophosphamide, and infusional doxorubicin) with a double dose of rituximab (SC-EPOCH-RR) to treat 11 patients with AIDS-related Burkitt lymphoma, researchers at the National Cancer Institute have observed progression-free survival of 100% and overall survival of 90% at a median follow-up of 73 months. This regimen omits systemic ifosfamide and high-dose methotrexate. Although both agents are thought to be important for disease control in Burkitt lymphoma, especially to treat and/or prevent lymphomatous CNS involvement, they also have substantial toxicities. In the NCI study, only 1 patient had CNS involvement at baseline and was successfully treated with intrathecal methotrexate alone. No patient relapsed in the CNS. However, given the small number of patients enrolled in this single institution study, there remains significant concern that omission of these agents will jeopardize disease control, specifically in high-risk patients. It will be interesting to see whether the results of the NCI study will be maintained in the ongoing larger cooperative group trial that currently evaluates dose-adjusted EPOCH-R.
Dr. Stefan K. Barta is with the Fox Chase Cancer Center/Temple University Health System in Philadelphia. He made his remarks in an editorial that accompanied the study.
For HIV-positive patients with Burkitt lymphoma, a modified intensive chemotherapy regimen produced overall and progression-free survival rates comparable with those seen in HIV-free patients with Burkitt, with manageable toxicities, reported researchers in a multicenter clinical trial.
The AIDS Malignancy Consortium (AMC) 048 study looked at the use of a modified version of the dose intensive CODOX-M/IVAC regimen, consisting of cyclophosphamide, vincristine, doxorubicin, high-dose methotrexate/ifosfamide, etoposide, and high-dose cytarabine. Compared with the standard regimen, the investigators added rituximab, reduced and/or rescheduled cyclophosphamide and methotrexate, limited the use of vincristine, and used combination intrathecal chemotherapy to prevent central nervous system involvement.
The study included 34 HIV-positive patients (30 men and 4 women) with Burkitt, 26 of whom were also receiving highly active antiretroviral therapy (HAART). The patients ranged in age from 19-55 (median 42) years. Of the 34 patients, 25 had Ann Arbor stage IV disease, 2 had stage III, 1 had stage IIE, 2 had stage II, and 4 had stage I. Median age was 42 years (range, 19-55 years).
The median CD4 count was 195 cells/mL; five patients had fewer than 100 cells/mL
Progression-free survival at 1 year was 69%, and 1- and 2-year overall survival were 72% and 69%, respectively.
The modified CODOX-M/IVAC regimen was associated with a grade 3 to 4 toxicity rate of 79%, with no grade 3 or 4 mucositis reported. In contrast, virtually all patients who receive the unmodified regimen develop at least one grade 3 or greater toxicity.
In total, there were 20 hematologic, 14 infectious, and 6 metabolic toxicities. Five patients did not complete treatment because of adverse events.
There were 11 deaths, including 1 treatment-related death of a patient with encephalopathy, hepatic failure, hepatitis B, and pneumonia cited as contributing causes. Of the remaining 10 patients, 8 died from systemic disease progression, and 2 died during follow-up, 1 during remission from a fungal infection and 1 from nonmalignant complications of HIV.
The investigators say that the addition of rituximab may have contributed to the favorable outcomes, and that rescheduling and limiting the amount of high-dose methotrexate delivered likely contributed to lower incidences of both severe mucositis and neutropenic fever.
Although a separate trial is evaluating a different regimen (EPOCH-R; etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab) in Burkitt lymphoma, “the modified AMC 048 version of CODOX-M/IVAC-R may better serve patients who present with CNS disease or are at high risk for CNS relapse (e.g., patients with bone marrow, testicular, or multiple extranodal sites), because it contains high-dose cytarabine and methotrexate, drugs that cross the blood-brain barrier. Consequently, AMC048 represents a reasonable treatment option in the appropriate setting, possibly irrespective of HIV status.”
The study by Dr. Ariela Noy from the Memorial Sloan Kettering Cancer Center in New York and her colleagues, is published in Blood.
For HIV-positive patients with Burkitt lymphoma, a modified intensive chemotherapy regimen produced overall and progression-free survival rates comparable with those seen in HIV-free patients with Burkitt, with manageable toxicities, reported researchers in a multicenter clinical trial.
The AIDS Malignancy Consortium (AMC) 048 study looked at the use of a modified version of the dose intensive CODOX-M/IVAC regimen, consisting of cyclophosphamide, vincristine, doxorubicin, high-dose methotrexate/ifosfamide, etoposide, and high-dose cytarabine. Compared with the standard regimen, the investigators added rituximab, reduced and/or rescheduled cyclophosphamide and methotrexate, limited the use of vincristine, and used combination intrathecal chemotherapy to prevent central nervous system involvement.
The study included 34 HIV-positive patients (30 men and 4 women) with Burkitt, 26 of whom were also receiving highly active antiretroviral therapy (HAART). The patients ranged in age from 19-55 (median 42) years. Of the 34 patients, 25 had Ann Arbor stage IV disease, 2 had stage III, 1 had stage IIE, 2 had stage II, and 4 had stage I. Median age was 42 years (range, 19-55 years).
The median CD4 count was 195 cells/mL; five patients had fewer than 100 cells/mL
Progression-free survival at 1 year was 69%, and 1- and 2-year overall survival were 72% and 69%, respectively.
The modified CODOX-M/IVAC regimen was associated with a grade 3 to 4 toxicity rate of 79%, with no grade 3 or 4 mucositis reported. In contrast, virtually all patients who receive the unmodified regimen develop at least one grade 3 or greater toxicity.
In total, there were 20 hematologic, 14 infectious, and 6 metabolic toxicities. Five patients did not complete treatment because of adverse events.
There were 11 deaths, including 1 treatment-related death of a patient with encephalopathy, hepatic failure, hepatitis B, and pneumonia cited as contributing causes. Of the remaining 10 patients, 8 died from systemic disease progression, and 2 died during follow-up, 1 during remission from a fungal infection and 1 from nonmalignant complications of HIV.
The investigators say that the addition of rituximab may have contributed to the favorable outcomes, and that rescheduling and limiting the amount of high-dose methotrexate delivered likely contributed to lower incidences of both severe mucositis and neutropenic fever.
Although a separate trial is evaluating a different regimen (EPOCH-R; etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab) in Burkitt lymphoma, “the modified AMC 048 version of CODOX-M/IVAC-R may better serve patients who present with CNS disease or are at high risk for CNS relapse (e.g., patients with bone marrow, testicular, or multiple extranodal sites), because it contains high-dose cytarabine and methotrexate, drugs that cross the blood-brain barrier. Consequently, AMC048 represents a reasonable treatment option in the appropriate setting, possibly irrespective of HIV status.”
The study by Dr. Ariela Noy from the Memorial Sloan Kettering Cancer Center in New York and her colleagues, is published in Blood.
FROM BLOOD
Key clinical point: A modified form of a standard chemotherapy regimen for Burkitt lymphoma is effective in HIV-positive patients, with lower rates of adverse events.
Major finding: 1-year overall survival was 72%, and 2-year OS was 69%.
Data source: Open-label study of a modified chemotherapy regimen in 34 HIV-positive patients with Burkitt lymphoma.
Disclosures: The trial was supported by a grant from the National Cancer Institute, The authors and Dr. Barta declare no conflicts of interest.
