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Interim PET provides limited prognostic value for diffuse large B-cell lymphoma
Results from positron emission tomography after 2 and 4 weeks of standardized, dose-dense chemotherapy in patients with diffuse large B-cell lymphoma (DLBCL) failed to provide sufficient prognostic accuracy to guide therapeutic decisions, according to a report published online in the Journal of Clinical Oncology.
“Our data demonstrate that interim PET-CT fails to deliver a PPV [positive predictive value] or NPV [negative predictive value] that reflects the clinical outcome for patients with DLBCL treated with R-CHOP-14 with sufficient accuracy to guide therapeutic decisions such as treatment intensification/deintensification at the present stage,” wrote Dr. Chrisoph Mamot of the division of haematology/oncology, Cantonal Hospital of Aarau, Switzerland, and colleagues (J. Clin. Onc. 2015 July 6 [doi:10.1200/JCO.2014.58.9846]).
Although the likelihood of 2-year event-free survival (EFS) was significantly lower among patients who had positive PET results after 2 weeks of therapy (PET-2-positive), compared with PET-2-negative patients (48% vs. 74%; P = .004), a large proportion of interim PET-positive patients had favorable outcomes. This may be due to the dose-dense regimen, Dr. Mamot and colleagues said.
Patients underwent six cycles of R-CHOP (rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, vincristine 1.4 mg/m2, and prednisone 100 mg/m2 for 5 days) every 14 days, followed by two cycles of rituximab.
Patients who had a positive PET-2 result received another PET scan after completion of four chemotherapy cycles. The 2-year EFS for PET-4-positive and PET-4-negative patients were not significantly different.
“Our original hypothesis that an interim PET/CT at a later time point might be able to better separate patients with good or poor prognosis was not confirmed,” the authors wrote. The end-of-treatment PET provided the best prediction of good vs. poor prognosis, but this time point is too late to adapt treatment. The authors concluded that interim PET/CT in patients with DLBCL presently is not accurate enough to guide treatment decisions in individual patients.
The multicenter, prospective study evaluated 138 patients, median age 58.5 years, who had untreated DLBCL, Ann Arbor stage I (12%), II (34%), III (23%), or IV (30%).
The study was supported by grants from Amgen (Switzerland) and OncoSuisse. Dr. Christoph Mamot reported consulting or advisory roles with Roche, Novartis, Amgen, and Boehringer-Ingelheim. Several of his coauthors reported ties to industry sources.
Results from positron emission tomography after 2 and 4 weeks of standardized, dose-dense chemotherapy in patients with diffuse large B-cell lymphoma (DLBCL) failed to provide sufficient prognostic accuracy to guide therapeutic decisions, according to a report published online in the Journal of Clinical Oncology.
“Our data demonstrate that interim PET-CT fails to deliver a PPV [positive predictive value] or NPV [negative predictive value] that reflects the clinical outcome for patients with DLBCL treated with R-CHOP-14 with sufficient accuracy to guide therapeutic decisions such as treatment intensification/deintensification at the present stage,” wrote Dr. Chrisoph Mamot of the division of haematology/oncology, Cantonal Hospital of Aarau, Switzerland, and colleagues (J. Clin. Onc. 2015 July 6 [doi:10.1200/JCO.2014.58.9846]).
Although the likelihood of 2-year event-free survival (EFS) was significantly lower among patients who had positive PET results after 2 weeks of therapy (PET-2-positive), compared with PET-2-negative patients (48% vs. 74%; P = .004), a large proportion of interim PET-positive patients had favorable outcomes. This may be due to the dose-dense regimen, Dr. Mamot and colleagues said.
Patients underwent six cycles of R-CHOP (rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, vincristine 1.4 mg/m2, and prednisone 100 mg/m2 for 5 days) every 14 days, followed by two cycles of rituximab.
Patients who had a positive PET-2 result received another PET scan after completion of four chemotherapy cycles. The 2-year EFS for PET-4-positive and PET-4-negative patients were not significantly different.
“Our original hypothesis that an interim PET/CT at a later time point might be able to better separate patients with good or poor prognosis was not confirmed,” the authors wrote. The end-of-treatment PET provided the best prediction of good vs. poor prognosis, but this time point is too late to adapt treatment. The authors concluded that interim PET/CT in patients with DLBCL presently is not accurate enough to guide treatment decisions in individual patients.
The multicenter, prospective study evaluated 138 patients, median age 58.5 years, who had untreated DLBCL, Ann Arbor stage I (12%), II (34%), III (23%), or IV (30%).
The study was supported by grants from Amgen (Switzerland) and OncoSuisse. Dr. Christoph Mamot reported consulting or advisory roles with Roche, Novartis, Amgen, and Boehringer-Ingelheim. Several of his coauthors reported ties to industry sources.
Results from positron emission tomography after 2 and 4 weeks of standardized, dose-dense chemotherapy in patients with diffuse large B-cell lymphoma (DLBCL) failed to provide sufficient prognostic accuracy to guide therapeutic decisions, according to a report published online in the Journal of Clinical Oncology.
“Our data demonstrate that interim PET-CT fails to deliver a PPV [positive predictive value] or NPV [negative predictive value] that reflects the clinical outcome for patients with DLBCL treated with R-CHOP-14 with sufficient accuracy to guide therapeutic decisions such as treatment intensification/deintensification at the present stage,” wrote Dr. Chrisoph Mamot of the division of haematology/oncology, Cantonal Hospital of Aarau, Switzerland, and colleagues (J. Clin. Onc. 2015 July 6 [doi:10.1200/JCO.2014.58.9846]).
Although the likelihood of 2-year event-free survival (EFS) was significantly lower among patients who had positive PET results after 2 weeks of therapy (PET-2-positive), compared with PET-2-negative patients (48% vs. 74%; P = .004), a large proportion of interim PET-positive patients had favorable outcomes. This may be due to the dose-dense regimen, Dr. Mamot and colleagues said.
Patients underwent six cycles of R-CHOP (rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, vincristine 1.4 mg/m2, and prednisone 100 mg/m2 for 5 days) every 14 days, followed by two cycles of rituximab.
Patients who had a positive PET-2 result received another PET scan after completion of four chemotherapy cycles. The 2-year EFS for PET-4-positive and PET-4-negative patients were not significantly different.
“Our original hypothesis that an interim PET/CT at a later time point might be able to better separate patients with good or poor prognosis was not confirmed,” the authors wrote. The end-of-treatment PET provided the best prediction of good vs. poor prognosis, but this time point is too late to adapt treatment. The authors concluded that interim PET/CT in patients with DLBCL presently is not accurate enough to guide treatment decisions in individual patients.
The multicenter, prospective study evaluated 138 patients, median age 58.5 years, who had untreated DLBCL, Ann Arbor stage I (12%), II (34%), III (23%), or IV (30%).
The study was supported by grants from Amgen (Switzerland) and OncoSuisse. Dr. Christoph Mamot reported consulting or advisory roles with Roche, Novartis, Amgen, and Boehringer-Ingelheim. Several of his coauthors reported ties to industry sources.
FROM JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: After two cycles of standardized, dose-dense chemotherapy in patients with diffuse large B-cell lymphoma (DLBCL), positive results from PET signaled worse 2-year event-free survival (EFS) than negative interim PET results, but overall survival was not significantly different.
Major finding: After two cycles of chemotherapy, 2-year EFS for PET-positive, compared with PET-negative patients was 48.2% vs. 74.2% (P = .004). Overall survival was 87.7% vs. 90.6% (P = .6).
Data source: The multicenter, prospective study evaluated 138 patients, median age 58.5 years, who had untreated DLBCL, Ann Arbor stage I (12%), II (34%), III (23%), or IV (30%).
Disclosures: The study was supported by grants from Amgen (Switzerland) and OncoSuisse. Dr. Christoph Mamot reported consulting or advisory roles with Roche, Novartis, Amgen, and Boehringer-Ingelheim. Several of his coauthors reported ties to industry sources.
Diffuse large B-cell lymphoma of the lung in a 63-year-old man with left flank pain
Diffuse large B-cell lymphoma of the lung is a rare entity, and although the prognosis is favorable, its biological features, clinical presentation, prognostic markers, and treatment have not been well defined.1,2 It is the second most common primary pulmonary lymphoma after mucosa-associated lymphoid tissue. PPL itself is very rare; it represents 3%-4% of extranodal non-Hodgkin lymphoma, less than 1% of NHL, and 0.5%-1.0% of primary pulmonary malignancies.2,3 A review of the literature indicates a lack of data on pulmonary DLBCL. The objective of this case report is to highlight areas in which further research may be pursued to better understand this disease.
Click on the PDF icon at the top of this introduction to read the full article.
Diffuse large B-cell lymphoma of the lung is a rare entity, and although the prognosis is favorable, its biological features, clinical presentation, prognostic markers, and treatment have not been well defined.1,2 It is the second most common primary pulmonary lymphoma after mucosa-associated lymphoid tissue. PPL itself is very rare; it represents 3%-4% of extranodal non-Hodgkin lymphoma, less than 1% of NHL, and 0.5%-1.0% of primary pulmonary malignancies.2,3 A review of the literature indicates a lack of data on pulmonary DLBCL. The objective of this case report is to highlight areas in which further research may be pursued to better understand this disease.
Click on the PDF icon at the top of this introduction to read the full article.
Diffuse large B-cell lymphoma of the lung is a rare entity, and although the prognosis is favorable, its biological features, clinical presentation, prognostic markers, and treatment have not been well defined.1,2 It is the second most common primary pulmonary lymphoma after mucosa-associated lymphoid tissue. PPL itself is very rare; it represents 3%-4% of extranodal non-Hodgkin lymphoma, less than 1% of NHL, and 0.5%-1.0% of primary pulmonary malignancies.2,3 A review of the literature indicates a lack of data on pulmonary DLBCL. The objective of this case report is to highlight areas in which further research may be pursued to better understand this disease.
Click on the PDF icon at the top of this introduction to read the full article.
Treated T-cells induce remissions in chemo-refractory B-cell lymphomas
NEW ORLEANS – A majority of patients with aggressive, treatment-refractory lymphomas had a complete or partial remission after being treated with chemotherapy and T-cells engineered to target the CD-19 receptor, National Cancer Institute investigators reported here.
In a study of 15 patients, 9 of whom had aggressive large-cell lymphomas and 6 of whom had indolent B-cell malignancies, 6 of 13 evaluable patients had a complete remission, 6 had a partial remission, and 1 had stable disease, said Dr. James N. Kochenderfer, an investigator in the Experimental Transplantation and Immunology Branch at the National Cancer Institute in Bethesda, Md.
One patient who, despite having undergone 10 prior therapies -- including 3 rituximab-based chemotherapy regimens -- continued to have lymphoma involvement of the liver and other abdominal areas, remains in complete remission 9 months after treatment with a chimeric antigen receptor (CAR) targeting the B-cell antigen CD19, Dr. Kochenderfer said at the American Society of Hematology annual meeting.
"We’ve chosen to focus on the aggressive large-cell lymphomas, because patients with these lymphomas, such as diffuse large B-cell lymphoma and primary mediastinal B-cell lymphoma, have a very poor prognosis if they are refractory to chemotherapy," he said in a briefing prior to his presentation of the results in oral session.
Commenting on the CAR-T cell strategy, Dr. Laurence Cooper of the University of Texas MD Anderson Cancer Center in Houston, who moderated the briefing, noted that "these patients were mortally wounded – they were all going to die, except that these types of engineered T-cell therapies rescued the patients."
The NCI investigators genetically modify each patient’s T-cells in vitro, using a gammaretroviral vector to induce in the cells expression of an anti-CD19 antibody. The process takes 10 days, during which time the patients receive cyclophosphamide and fludarabine to deplete their endogenous leukocytes.
"There’s extensive evidence in multiple animal models and also in humans that shows that depletion of endogenous lymphocytes dramatically enhances the activity of adoptively transferred T-cells. In mouse models, it’s absolutely critical for effectiveness of these CAR T-cells," Dr. Kochenderfer said.
The patients are then infused with the anti-C19-CAR transduced T-cells.
The investigators thus far have treated 15 patients with the technique, including, as noted before, 9 with chemo-refractory large cell lymphomas.
Treatment toxicities included hypotension and neurological toxicities such as confusion, delirium, and transient aphasia.
"Another thing about this therapy that’s amazing is that the patients do become sick; we previously published that the toxicity correlates with serum cytokine levels. [However] they recover very quickly: they can go from being incredibly ill to completely feeling almost normal within 2 days," Dr. Kochenderfer noted.
He and his colleagues also have used the technique in 10 patients who had persistent B-cell malignancies or other cancers following allogeneic stem cell transplantation as an alternative to donor lymphocyte infusions, which have shown inconsistent efficacy and are associated with significant risk for morbidity and mortality for graft-versus-host disease (GvHD).
Of 10 patients treated to date, 3 had "substantial regression" of their malignancies, and one patient with chronic lymphoctic leukemia (CLL) is still in complete remission 12 months after treatment. Another CLL patient had tumor lysis syndrome as he experienced regression of CLL in his bone marrow, blood, and lymph nodes. A patient with the notoriously treatment-refractory mantle cell lymphoma had a partial remission.
As in the first study, toxicities were manageable and consisted mainly of fever, hypotension, and B-cell depletion. No patients developed GvHD after infusion of the altered T-cells.
The study was funded by the National Cancer Institute and by Kite Pharma. Dr. Kochenderfer and Dr. Cooper reported having no conflicts of interest to disclose.
NEW ORLEANS – A majority of patients with aggressive, treatment-refractory lymphomas had a complete or partial remission after being treated with chemotherapy and T-cells engineered to target the CD-19 receptor, National Cancer Institute investigators reported here.
In a study of 15 patients, 9 of whom had aggressive large-cell lymphomas and 6 of whom had indolent B-cell malignancies, 6 of 13 evaluable patients had a complete remission, 6 had a partial remission, and 1 had stable disease, said Dr. James N. Kochenderfer, an investigator in the Experimental Transplantation and Immunology Branch at the National Cancer Institute in Bethesda, Md.
One patient who, despite having undergone 10 prior therapies -- including 3 rituximab-based chemotherapy regimens -- continued to have lymphoma involvement of the liver and other abdominal areas, remains in complete remission 9 months after treatment with a chimeric antigen receptor (CAR) targeting the B-cell antigen CD19, Dr. Kochenderfer said at the American Society of Hematology annual meeting.
"We’ve chosen to focus on the aggressive large-cell lymphomas, because patients with these lymphomas, such as diffuse large B-cell lymphoma and primary mediastinal B-cell lymphoma, have a very poor prognosis if they are refractory to chemotherapy," he said in a briefing prior to his presentation of the results in oral session.
Commenting on the CAR-T cell strategy, Dr. Laurence Cooper of the University of Texas MD Anderson Cancer Center in Houston, who moderated the briefing, noted that "these patients were mortally wounded – they were all going to die, except that these types of engineered T-cell therapies rescued the patients."
The NCI investigators genetically modify each patient’s T-cells in vitro, using a gammaretroviral vector to induce in the cells expression of an anti-CD19 antibody. The process takes 10 days, during which time the patients receive cyclophosphamide and fludarabine to deplete their endogenous leukocytes.
"There’s extensive evidence in multiple animal models and also in humans that shows that depletion of endogenous lymphocytes dramatically enhances the activity of adoptively transferred T-cells. In mouse models, it’s absolutely critical for effectiveness of these CAR T-cells," Dr. Kochenderfer said.
The patients are then infused with the anti-C19-CAR transduced T-cells.
The investigators thus far have treated 15 patients with the technique, including, as noted before, 9 with chemo-refractory large cell lymphomas.
Treatment toxicities included hypotension and neurological toxicities such as confusion, delirium, and transient aphasia.
"Another thing about this therapy that’s amazing is that the patients do become sick; we previously published that the toxicity correlates with serum cytokine levels. [However] they recover very quickly: they can go from being incredibly ill to completely feeling almost normal within 2 days," Dr. Kochenderfer noted.
He and his colleagues also have used the technique in 10 patients who had persistent B-cell malignancies or other cancers following allogeneic stem cell transplantation as an alternative to donor lymphocyte infusions, which have shown inconsistent efficacy and are associated with significant risk for morbidity and mortality for graft-versus-host disease (GvHD).
Of 10 patients treated to date, 3 had "substantial regression" of their malignancies, and one patient with chronic lymphoctic leukemia (CLL) is still in complete remission 12 months after treatment. Another CLL patient had tumor lysis syndrome as he experienced regression of CLL in his bone marrow, blood, and lymph nodes. A patient with the notoriously treatment-refractory mantle cell lymphoma had a partial remission.
As in the first study, toxicities were manageable and consisted mainly of fever, hypotension, and B-cell depletion. No patients developed GvHD after infusion of the altered T-cells.
The study was funded by the National Cancer Institute and by Kite Pharma. Dr. Kochenderfer and Dr. Cooper reported having no conflicts of interest to disclose.
NEW ORLEANS – A majority of patients with aggressive, treatment-refractory lymphomas had a complete or partial remission after being treated with chemotherapy and T-cells engineered to target the CD-19 receptor, National Cancer Institute investigators reported here.
In a study of 15 patients, 9 of whom had aggressive large-cell lymphomas and 6 of whom had indolent B-cell malignancies, 6 of 13 evaluable patients had a complete remission, 6 had a partial remission, and 1 had stable disease, said Dr. James N. Kochenderfer, an investigator in the Experimental Transplantation and Immunology Branch at the National Cancer Institute in Bethesda, Md.
One patient who, despite having undergone 10 prior therapies -- including 3 rituximab-based chemotherapy regimens -- continued to have lymphoma involvement of the liver and other abdominal areas, remains in complete remission 9 months after treatment with a chimeric antigen receptor (CAR) targeting the B-cell antigen CD19, Dr. Kochenderfer said at the American Society of Hematology annual meeting.
"We’ve chosen to focus on the aggressive large-cell lymphomas, because patients with these lymphomas, such as diffuse large B-cell lymphoma and primary mediastinal B-cell lymphoma, have a very poor prognosis if they are refractory to chemotherapy," he said in a briefing prior to his presentation of the results in oral session.
Commenting on the CAR-T cell strategy, Dr. Laurence Cooper of the University of Texas MD Anderson Cancer Center in Houston, who moderated the briefing, noted that "these patients were mortally wounded – they were all going to die, except that these types of engineered T-cell therapies rescued the patients."
The NCI investigators genetically modify each patient’s T-cells in vitro, using a gammaretroviral vector to induce in the cells expression of an anti-CD19 antibody. The process takes 10 days, during which time the patients receive cyclophosphamide and fludarabine to deplete their endogenous leukocytes.
"There’s extensive evidence in multiple animal models and also in humans that shows that depletion of endogenous lymphocytes dramatically enhances the activity of adoptively transferred T-cells. In mouse models, it’s absolutely critical for effectiveness of these CAR T-cells," Dr. Kochenderfer said.
The patients are then infused with the anti-C19-CAR transduced T-cells.
The investigators thus far have treated 15 patients with the technique, including, as noted before, 9 with chemo-refractory large cell lymphomas.
Treatment toxicities included hypotension and neurological toxicities such as confusion, delirium, and transient aphasia.
"Another thing about this therapy that’s amazing is that the patients do become sick; we previously published that the toxicity correlates with serum cytokine levels. [However] they recover very quickly: they can go from being incredibly ill to completely feeling almost normal within 2 days," Dr. Kochenderfer noted.
He and his colleagues also have used the technique in 10 patients who had persistent B-cell malignancies or other cancers following allogeneic stem cell transplantation as an alternative to donor lymphocyte infusions, which have shown inconsistent efficacy and are associated with significant risk for morbidity and mortality for graft-versus-host disease (GvHD).
Of 10 patients treated to date, 3 had "substantial regression" of their malignancies, and one patient with chronic lymphoctic leukemia (CLL) is still in complete remission 12 months after treatment. Another CLL patient had tumor lysis syndrome as he experienced regression of CLL in his bone marrow, blood, and lymph nodes. A patient with the notoriously treatment-refractory mantle cell lymphoma had a partial remission.
As in the first study, toxicities were manageable and consisted mainly of fever, hypotension, and B-cell depletion. No patients developed GvHD after infusion of the altered T-cells.
The study was funded by the National Cancer Institute and by Kite Pharma. Dr. Kochenderfer and Dr. Cooper reported having no conflicts of interest to disclose.
AT ASH 2013
Major finding: Among evaluable patient treated with chimeric antigen receptor expressing T cells, 12 of 13 had complete or partial remissions, and the remaining patient had stable disease.
Data source: Prospective clinical trial in 15 patients with chemo-resistant aggressive large-cell or indolent lymphomas.
Disclosures: The study was funded by the National Cancer Institute and by Kite Pharma. Dr. Kochenderfer and Dr. Cooper reported having no conflicts of interest to disclose.
Dawn of a new era: targeting the B-cell receptor signaling pathway to conquer B-cell lymphomas
Despite the advent of modern chemo- and radioimmunotherapies, the disease course in most mature B-cell malignancies (with the exception of diffuse large B-cell lymphoma [DLBCL] and Burkitt lymphoma) is highlighted by frequent relapses, progressively shorter remissions, and eventual emergence of therapy resistance. An effective salvage therapy in this setting remains an area of unmet medical need. Bruton’s tyrosine kinase (BTK) is a critical component of B-cell–receptor signaling that mediates interactions with the tumor microenvironment and promotes survival and proliferation of malignant B-cells.1,2 The BTK protein itself is a Tec family tyrosine kinase that is activated by spleen tyrosine kinase following B-cell-receptor stimulation and which is then required for downstream events including calcium release, activation of the NFB and NFAT pathways, cell survival and proliferation.1 The fundamental role of BTK in B-cell function is underscored by the human disease X-linked agammaglobulinemia, which is caused by loss of function mutations in BTK.3 These mutations result in the virtual absence of all B cells and immunoglobulins, leading to recurrent bacterial infections. Ibrutinib (formally known as PCI-32765) is the first-in-class BTK inhibitor to enter clinical trials. In a multicenter phase 1 dose-escalating study, 56 patients with relapsed or refractory B-cell lymphomas received escalated doses of oral ibrutinib either on an intermittent or continuous daily dosing schedule.4 The most common adverse effects were grade 1-2 nonhematologic toxicities, which included rash, nausea, fatigue, diarrhea, muscle spasms/myalgia, and arthralgia. An overall response rate (ORR) of 60% was achieved across all histological types with the best efficacy seen in patients with mantle cell lymphoma (MCL; 78%) and chronic lymphocytic leukemia (CLL; 68%).
Click on the PDF icon at the top of this article to read the full article.
Despite the advent of modern chemo- and radioimmunotherapies, the disease course in most mature B-cell malignancies (with the exception of diffuse large B-cell lymphoma [DLBCL] and Burkitt lymphoma) is highlighted by frequent relapses, progressively shorter remissions, and eventual emergence of therapy resistance. An effective salvage therapy in this setting remains an area of unmet medical need. Bruton’s tyrosine kinase (BTK) is a critical component of B-cell–receptor signaling that mediates interactions with the tumor microenvironment and promotes survival and proliferation of malignant B-cells.1,2 The BTK protein itself is a Tec family tyrosine kinase that is activated by spleen tyrosine kinase following B-cell-receptor stimulation and which is then required for downstream events including calcium release, activation of the NFB and NFAT pathways, cell survival and proliferation.1 The fundamental role of BTK in B-cell function is underscored by the human disease X-linked agammaglobulinemia, which is caused by loss of function mutations in BTK.3 These mutations result in the virtual absence of all B cells and immunoglobulins, leading to recurrent bacterial infections. Ibrutinib (formally known as PCI-32765) is the first-in-class BTK inhibitor to enter clinical trials. In a multicenter phase 1 dose-escalating study, 56 patients with relapsed or refractory B-cell lymphomas received escalated doses of oral ibrutinib either on an intermittent or continuous daily dosing schedule.4 The most common adverse effects were grade 1-2 nonhematologic toxicities, which included rash, nausea, fatigue, diarrhea, muscle spasms/myalgia, and arthralgia. An overall response rate (ORR) of 60% was achieved across all histological types with the best efficacy seen in patients with mantle cell lymphoma (MCL; 78%) and chronic lymphocytic leukemia (CLL; 68%).
Click on the PDF icon at the top of this article to read the full article.
Despite the advent of modern chemo- and radioimmunotherapies, the disease course in most mature B-cell malignancies (with the exception of diffuse large B-cell lymphoma [DLBCL] and Burkitt lymphoma) is highlighted by frequent relapses, progressively shorter remissions, and eventual emergence of therapy resistance. An effective salvage therapy in this setting remains an area of unmet medical need. Bruton’s tyrosine kinase (BTK) is a critical component of B-cell–receptor signaling that mediates interactions with the tumor microenvironment and promotes survival and proliferation of malignant B-cells.1,2 The BTK protein itself is a Tec family tyrosine kinase that is activated by spleen tyrosine kinase following B-cell-receptor stimulation and which is then required for downstream events including calcium release, activation of the NFB and NFAT pathways, cell survival and proliferation.1 The fundamental role of BTK in B-cell function is underscored by the human disease X-linked agammaglobulinemia, which is caused by loss of function mutations in BTK.3 These mutations result in the virtual absence of all B cells and immunoglobulins, leading to recurrent bacterial infections. Ibrutinib (formally known as PCI-32765) is the first-in-class BTK inhibitor to enter clinical trials. In a multicenter phase 1 dose-escalating study, 56 patients with relapsed or refractory B-cell lymphomas received escalated doses of oral ibrutinib either on an intermittent or continuous daily dosing schedule.4 The most common adverse effects were grade 1-2 nonhematologic toxicities, which included rash, nausea, fatigue, diarrhea, muscle spasms/myalgia, and arthralgia. An overall response rate (ORR) of 60% was achieved across all histological types with the best efficacy seen in patients with mantle cell lymphoma (MCL; 78%) and chronic lymphocytic leukemia (CLL; 68%).
Click on the PDF icon at the top of this article to read the full article.
Rituximab may obviate radiation in mediastinal B-cell lymphoma
Adding rituximab to combination chemotherapy for primary mediastinal B-cell lymphoma yields a high cure rate and may obviate the need for thoracic radiation therapy, a study has shown.
Patients in a single-group, prospective phase II study were treated with dose-adjusted etoposide, doxorubicin, cyclophosphamide with vincristine, prednisone, and rituximab (DA-EPOCH-R). All but 2 of the 51 adults with lymphoma in the study were able to forgo radiotherapy, and there were no recurrences during a median follow-up of 5 years, reported Dr. Kieron Dunleavy of the National Cancer Institute and his colleagues.
"These findings suggest that DA-EPOCH-R is a therapeutic advance for this type of lymphoma," they wrote (N. Engl. J. Med. 2013;368:1408-16 [doi:10.1056/NEJMoa1214561]).
In a previous study, Dr. Dunleavy and his colleagues found that DA-EPOCH yielded an overall survival of 79%. To examine whether the addition of rituximab would further improve outcomes, they enrolled treatment-naive patients who had masses of at least 5 cm and presented over a 13-year period.
The study patients’ median age was 30 years (range, 19-52 years), and 59% were women. Mediastinal B-cell lymphoma was advanced, with a median tumor diameter of 11 cm. Approximately 30% of patients had stage IV disease.
All 51 patients received six to eight cycles of DA-EPOCH-R. Two patients showed persistent focal disease after therapy, and one patient showed disease progression. Two of the patients then underwent mediastinal radiotherapy, and one underwent excisional biopsy. All three were disease free thereafter.
After follow-up, ranging from 3 to 156 months, overall survival was 97% and event-free survival was 93%, with no recurrences of the cancer, the investigators reported.
Primary mediastinal B-cell lymphoma develops in the thymus, "predominantly affects young women, is aggressive, and typically is manifested by a localized, bulky mediastinal mass, often with pleural and pericardial effusions," they noted. There have been few prospective studies of the disease; and the findings have been conflicting, so at present there are no treatment standards. Immunochemotherapy usually does not achieve tumor control. Mediastinal radiotherapy (associated with severe late adverse effects) after aggressive chemotherapy is the current regimen.
The toxic effects of the chemotherapy regimen were similar to other previously reported events. Neutropenia occurred during half of the chemotherapy cycles overall, thrombocytopenia occurred in 6%, and hospitalization was required for fever and neutropenia in 13% of the cycles. There were no significant cardiac toxic effects.
Dr. Dunleavy and his associates also reported the results of DA-EPOCH-R therapy in an independent retrospective cohort of 16 patients treated at Stanford (Calif.) University Medical Center during the past 5 years. All of the Stanford patients were able to forgo radiation therapy, and event-free survival was 100%.
An international trial of DA-EPOCH-R for treating children or adolescents with primary mediastinal B-cell lymphoma is currently underway (clinical trial number NCT01516567).
The study was supported by the National Cancer Institute. Amgen provided filgrastim for the study but had no involvement with study design or with data collection or analysis. The investigators reported having no relevant financial conflicts.
Adding rituximab to combination chemotherapy for primary mediastinal B-cell lymphoma yields a high cure rate and may obviate the need for thoracic radiation therapy, a study has shown.
Patients in a single-group, prospective phase II study were treated with dose-adjusted etoposide, doxorubicin, cyclophosphamide with vincristine, prednisone, and rituximab (DA-EPOCH-R). All but 2 of the 51 adults with lymphoma in the study were able to forgo radiotherapy, and there were no recurrences during a median follow-up of 5 years, reported Dr. Kieron Dunleavy of the National Cancer Institute and his colleagues.
"These findings suggest that DA-EPOCH-R is a therapeutic advance for this type of lymphoma," they wrote (N. Engl. J. Med. 2013;368:1408-16 [doi:10.1056/NEJMoa1214561]).
In a previous study, Dr. Dunleavy and his colleagues found that DA-EPOCH yielded an overall survival of 79%. To examine whether the addition of rituximab would further improve outcomes, they enrolled treatment-naive patients who had masses of at least 5 cm and presented over a 13-year period.
The study patients’ median age was 30 years (range, 19-52 years), and 59% were women. Mediastinal B-cell lymphoma was advanced, with a median tumor diameter of 11 cm. Approximately 30% of patients had stage IV disease.
All 51 patients received six to eight cycles of DA-EPOCH-R. Two patients showed persistent focal disease after therapy, and one patient showed disease progression. Two of the patients then underwent mediastinal radiotherapy, and one underwent excisional biopsy. All three were disease free thereafter.
After follow-up, ranging from 3 to 156 months, overall survival was 97% and event-free survival was 93%, with no recurrences of the cancer, the investigators reported.
Primary mediastinal B-cell lymphoma develops in the thymus, "predominantly affects young women, is aggressive, and typically is manifested by a localized, bulky mediastinal mass, often with pleural and pericardial effusions," they noted. There have been few prospective studies of the disease; and the findings have been conflicting, so at present there are no treatment standards. Immunochemotherapy usually does not achieve tumor control. Mediastinal radiotherapy (associated with severe late adverse effects) after aggressive chemotherapy is the current regimen.
The toxic effects of the chemotherapy regimen were similar to other previously reported events. Neutropenia occurred during half of the chemotherapy cycles overall, thrombocytopenia occurred in 6%, and hospitalization was required for fever and neutropenia in 13% of the cycles. There were no significant cardiac toxic effects.
Dr. Dunleavy and his associates also reported the results of DA-EPOCH-R therapy in an independent retrospective cohort of 16 patients treated at Stanford (Calif.) University Medical Center during the past 5 years. All of the Stanford patients were able to forgo radiation therapy, and event-free survival was 100%.
An international trial of DA-EPOCH-R for treating children or adolescents with primary mediastinal B-cell lymphoma is currently underway (clinical trial number NCT01516567).
The study was supported by the National Cancer Institute. Amgen provided filgrastim for the study but had no involvement with study design or with data collection or analysis. The investigators reported having no relevant financial conflicts.
Adding rituximab to combination chemotherapy for primary mediastinal B-cell lymphoma yields a high cure rate and may obviate the need for thoracic radiation therapy, a study has shown.
Patients in a single-group, prospective phase II study were treated with dose-adjusted etoposide, doxorubicin, cyclophosphamide with vincristine, prednisone, and rituximab (DA-EPOCH-R). All but 2 of the 51 adults with lymphoma in the study were able to forgo radiotherapy, and there were no recurrences during a median follow-up of 5 years, reported Dr. Kieron Dunleavy of the National Cancer Institute and his colleagues.
"These findings suggest that DA-EPOCH-R is a therapeutic advance for this type of lymphoma," they wrote (N. Engl. J. Med. 2013;368:1408-16 [doi:10.1056/NEJMoa1214561]).
In a previous study, Dr. Dunleavy and his colleagues found that DA-EPOCH yielded an overall survival of 79%. To examine whether the addition of rituximab would further improve outcomes, they enrolled treatment-naive patients who had masses of at least 5 cm and presented over a 13-year period.
The study patients’ median age was 30 years (range, 19-52 years), and 59% were women. Mediastinal B-cell lymphoma was advanced, with a median tumor diameter of 11 cm. Approximately 30% of patients had stage IV disease.
All 51 patients received six to eight cycles of DA-EPOCH-R. Two patients showed persistent focal disease after therapy, and one patient showed disease progression. Two of the patients then underwent mediastinal radiotherapy, and one underwent excisional biopsy. All three were disease free thereafter.
After follow-up, ranging from 3 to 156 months, overall survival was 97% and event-free survival was 93%, with no recurrences of the cancer, the investigators reported.
Primary mediastinal B-cell lymphoma develops in the thymus, "predominantly affects young women, is aggressive, and typically is manifested by a localized, bulky mediastinal mass, often with pleural and pericardial effusions," they noted. There have been few prospective studies of the disease; and the findings have been conflicting, so at present there are no treatment standards. Immunochemotherapy usually does not achieve tumor control. Mediastinal radiotherapy (associated with severe late adverse effects) after aggressive chemotherapy is the current regimen.
The toxic effects of the chemotherapy regimen were similar to other previously reported events. Neutropenia occurred during half of the chemotherapy cycles overall, thrombocytopenia occurred in 6%, and hospitalization was required for fever and neutropenia in 13% of the cycles. There were no significant cardiac toxic effects.
Dr. Dunleavy and his associates also reported the results of DA-EPOCH-R therapy in an independent retrospective cohort of 16 patients treated at Stanford (Calif.) University Medical Center during the past 5 years. All of the Stanford patients were able to forgo radiation therapy, and event-free survival was 100%.
An international trial of DA-EPOCH-R for treating children or adolescents with primary mediastinal B-cell lymphoma is currently underway (clinical trial number NCT01516567).
The study was supported by the National Cancer Institute. Amgen provided filgrastim for the study but had no involvement with study design or with data collection or analysis. The investigators reported having no relevant financial conflicts.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Major finding: Overall survival was 97% in adults treated with DA-EPOCH-R, and event-free survival was 93%.
Data source: A phase II, prospective clinical trial of 51 adults with primary mediastinal B-cell lymphoma who were followed for a median of 5 years.
Disclosures: The study was supported by the National Cancer Institute. Amgen provided filgrastim for the study but had no involvement with study design or with data collection or analysis. The investigators reported having no relevant financial conflicts.
Interim FDG-PET 'Not Justified' in Diffuse Large B-Cell Lymphoma
LONDON – There is no benefit of performing 18fluorodeoxyglucose positron emission tomography after the first cycle of treatment in patients with diffuse large B-cell lymphoma or primary mediastinal large B-cell lymphoma, the results of an Italian study suggest.
The imaging technique failed to pick up signs of disease in 10 of 85 (12%) of patients who later relapsed following treatment with R-CHOP (rituximab [Rituxan], cyclophosphamide [Cytoxan], hydroxydaunorubicin [doxorubicin, Adriamycin], Oncovin [vincristine], and prednisolone) in conjunction with radiotherapy.
Interim 18FDG-PET was associated with a positive predictive value (PPV) of just 58% and a negative predictive value (NPV) of 77%. By comparison, the PPV and NPV of 18FDG-PET performed after the last treatment cycle were higher, at 70% and 82%, respectively.
"The early identification of nonresponders might be a pivotal step for cure of diffuse large B-cell lymphoma (DLBCL), said study investigator Dr. M. Christina Cox, who presented the findings at the annual congress of the European Hematology Association.
Dr. Cox of the Azienda Ospedaliera Sant’ Andrea in Rome explained that the use of the imaging method early on in the treatment of Hodgkin’s lymphoma had been shown to be a strong predictor of outcome, allowing earlier adjustment of therapy.
"From 2005, several studies showed than in [DLBCL], interim PET might be predictive of event-free survival, progression-free survival, and overall survival," Dr. Cox said. However, "more recent studies have yielded heterogeneous results."
Aiming to clarify the issue, Dr. Cox and colleagues undertook a prospective study of treatment-naive patients with either DLBCL (72 patients) or primary mediastinal large B-cell lymphoma (PMLBCL, 13 patients) enrolled between April 2005 and April 2010. Patients were eligible for the study if they had already undergone a PET or contrast enhancement computed tomography (CECT) scan, had no CNS involvement, were HIV negative, and were not eligible for R-CHOP-like treatments.
After initial staging with 18FDG-PET and CECT, patients with stage II or higher DLCBL received six cycles of treatment with either R-CHOP-14 if they were younger than 70 years or R-CHOP-21 if they were aged 70 years or older. In both cases, the duration of treatment was reduced to three cycles for patients with stage I disease. Patients with PMLBCL were treated with R-MACOP-14 (rituximab, methotrexate, ara-C [cytarabine], cyclophosphamide, Oncovin [vincristine], and prednisone) for 12 weeks. All patients with PMLBCL and those with stage I DLCBL received radiotherapy.
Interim staging using PET and CECT was performed within 10-20 days of the first cycle of treatment, with the final scans using both imaging techniques taken 6-8 weeks after the last treatment. The recently validated Deauville 5-point scale was used to compare the differences between interim and final PET scans. This scale gauges the uptake of 18FDG within the tissues.
The minimum observation time was set at 2 years, unless a DLBCL event occurred earlier. Targeted biopsies were performed at the end of treatment if there was a mismatch between PET and CECT results, and at the interim stage if results were conflicting and the site in need of biopsy was easy to reach.
Almost two-thirds (62%) were biopsy negative. Dr. Cox noted that none of the interim PET, biopsy-negative patients relapsed.
At a median follow-up of almost 3 years, 70 (82.3%) patients were still alive, with 65 (76.4%) being disease free after first- or second-line therapy. One-fifth had been refractory to first-line treatment. Of these patients, 78% had a positive interim PET scan.
Looking at factors that might predict the achievement of a complete remission to first-line treatment, only the interim CECT results were statistically significant in a multivariate analysis (P less than .002).
In addition, only the final PET scan was predictive of both overall and progression-free survival, whereas interim and final CECT were both predictive.
"In this series, interim PET proved not to be a robust tool for the early shifting of patients to high-dose therapy," Dr. Cox reported. She added that compared with interim CECT and final PET, "interim PET was not really of adjunctive value." Indeed, most refractory patients (61%) were identified by interim CECT.
"We think that the use of this [interim PET] expensive, radioactive, and emotionally distressing tool is presently not justified outside of clinical trials."
Commenting on the findings in an interview, Dr. Andrew Pettitt, professor of hematological oncology at the University of Liverpool (England), said that although it was a good study, he was not convinced it was adequately powered to draw such a definitive conclusion. "I also have some reservations of the PET-CT reporting and quality control," Dr. Pettitt, who was not involved in the study. "It’s very provocative, but I don’t think it’s definitive."
Dr. Cox and Dr. Pettitt stated that they had no relevant financial disclosures.
R-CHOP, radiotherapy, 18FDG-PET, Dr. M. Christina Cox, the European Hematology Association,
LONDON – There is no benefit of performing 18fluorodeoxyglucose positron emission tomography after the first cycle of treatment in patients with diffuse large B-cell lymphoma or primary mediastinal large B-cell lymphoma, the results of an Italian study suggest.
The imaging technique failed to pick up signs of disease in 10 of 85 (12%) of patients who later relapsed following treatment with R-CHOP (rituximab [Rituxan], cyclophosphamide [Cytoxan], hydroxydaunorubicin [doxorubicin, Adriamycin], Oncovin [vincristine], and prednisolone) in conjunction with radiotherapy.
Interim 18FDG-PET was associated with a positive predictive value (PPV) of just 58% and a negative predictive value (NPV) of 77%. By comparison, the PPV and NPV of 18FDG-PET performed after the last treatment cycle were higher, at 70% and 82%, respectively.
"The early identification of nonresponders might be a pivotal step for cure of diffuse large B-cell lymphoma (DLBCL), said study investigator Dr. M. Christina Cox, who presented the findings at the annual congress of the European Hematology Association.
Dr. Cox of the Azienda Ospedaliera Sant’ Andrea in Rome explained that the use of the imaging method early on in the treatment of Hodgkin’s lymphoma had been shown to be a strong predictor of outcome, allowing earlier adjustment of therapy.
"From 2005, several studies showed than in [DLBCL], interim PET might be predictive of event-free survival, progression-free survival, and overall survival," Dr. Cox said. However, "more recent studies have yielded heterogeneous results."
Aiming to clarify the issue, Dr. Cox and colleagues undertook a prospective study of treatment-naive patients with either DLBCL (72 patients) or primary mediastinal large B-cell lymphoma (PMLBCL, 13 patients) enrolled between April 2005 and April 2010. Patients were eligible for the study if they had already undergone a PET or contrast enhancement computed tomography (CECT) scan, had no CNS involvement, were HIV negative, and were not eligible for R-CHOP-like treatments.
After initial staging with 18FDG-PET and CECT, patients with stage II or higher DLCBL received six cycles of treatment with either R-CHOP-14 if they were younger than 70 years or R-CHOP-21 if they were aged 70 years or older. In both cases, the duration of treatment was reduced to three cycles for patients with stage I disease. Patients with PMLBCL were treated with R-MACOP-14 (rituximab, methotrexate, ara-C [cytarabine], cyclophosphamide, Oncovin [vincristine], and prednisone) for 12 weeks. All patients with PMLBCL and those with stage I DLCBL received radiotherapy.
Interim staging using PET and CECT was performed within 10-20 days of the first cycle of treatment, with the final scans using both imaging techniques taken 6-8 weeks after the last treatment. The recently validated Deauville 5-point scale was used to compare the differences between interim and final PET scans. This scale gauges the uptake of 18FDG within the tissues.
The minimum observation time was set at 2 years, unless a DLBCL event occurred earlier. Targeted biopsies were performed at the end of treatment if there was a mismatch between PET and CECT results, and at the interim stage if results were conflicting and the site in need of biopsy was easy to reach.
Almost two-thirds (62%) were biopsy negative. Dr. Cox noted that none of the interim PET, biopsy-negative patients relapsed.
At a median follow-up of almost 3 years, 70 (82.3%) patients were still alive, with 65 (76.4%) being disease free after first- or second-line therapy. One-fifth had been refractory to first-line treatment. Of these patients, 78% had a positive interim PET scan.
Looking at factors that might predict the achievement of a complete remission to first-line treatment, only the interim CECT results were statistically significant in a multivariate analysis (P less than .002).
In addition, only the final PET scan was predictive of both overall and progression-free survival, whereas interim and final CECT were both predictive.
"In this series, interim PET proved not to be a robust tool for the early shifting of patients to high-dose therapy," Dr. Cox reported. She added that compared with interim CECT and final PET, "interim PET was not really of adjunctive value." Indeed, most refractory patients (61%) were identified by interim CECT.
"We think that the use of this [interim PET] expensive, radioactive, and emotionally distressing tool is presently not justified outside of clinical trials."
Commenting on the findings in an interview, Dr. Andrew Pettitt, professor of hematological oncology at the University of Liverpool (England), said that although it was a good study, he was not convinced it was adequately powered to draw such a definitive conclusion. "I also have some reservations of the PET-CT reporting and quality control," Dr. Pettitt, who was not involved in the study. "It’s very provocative, but I don’t think it’s definitive."
Dr. Cox and Dr. Pettitt stated that they had no relevant financial disclosures.
LONDON – There is no benefit of performing 18fluorodeoxyglucose positron emission tomography after the first cycle of treatment in patients with diffuse large B-cell lymphoma or primary mediastinal large B-cell lymphoma, the results of an Italian study suggest.
The imaging technique failed to pick up signs of disease in 10 of 85 (12%) of patients who later relapsed following treatment with R-CHOP (rituximab [Rituxan], cyclophosphamide [Cytoxan], hydroxydaunorubicin [doxorubicin, Adriamycin], Oncovin [vincristine], and prednisolone) in conjunction with radiotherapy.
Interim 18FDG-PET was associated with a positive predictive value (PPV) of just 58% and a negative predictive value (NPV) of 77%. By comparison, the PPV and NPV of 18FDG-PET performed after the last treatment cycle were higher, at 70% and 82%, respectively.
"The early identification of nonresponders might be a pivotal step for cure of diffuse large B-cell lymphoma (DLBCL), said study investigator Dr. M. Christina Cox, who presented the findings at the annual congress of the European Hematology Association.
Dr. Cox of the Azienda Ospedaliera Sant’ Andrea in Rome explained that the use of the imaging method early on in the treatment of Hodgkin’s lymphoma had been shown to be a strong predictor of outcome, allowing earlier adjustment of therapy.
"From 2005, several studies showed than in [DLBCL], interim PET might be predictive of event-free survival, progression-free survival, and overall survival," Dr. Cox said. However, "more recent studies have yielded heterogeneous results."
Aiming to clarify the issue, Dr. Cox and colleagues undertook a prospective study of treatment-naive patients with either DLBCL (72 patients) or primary mediastinal large B-cell lymphoma (PMLBCL, 13 patients) enrolled between April 2005 and April 2010. Patients were eligible for the study if they had already undergone a PET or contrast enhancement computed tomography (CECT) scan, had no CNS involvement, were HIV negative, and were not eligible for R-CHOP-like treatments.
After initial staging with 18FDG-PET and CECT, patients with stage II or higher DLCBL received six cycles of treatment with either R-CHOP-14 if they were younger than 70 years or R-CHOP-21 if they were aged 70 years or older. In both cases, the duration of treatment was reduced to three cycles for patients with stage I disease. Patients with PMLBCL were treated with R-MACOP-14 (rituximab, methotrexate, ara-C [cytarabine], cyclophosphamide, Oncovin [vincristine], and prednisone) for 12 weeks. All patients with PMLBCL and those with stage I DLCBL received radiotherapy.
Interim staging using PET and CECT was performed within 10-20 days of the first cycle of treatment, with the final scans using both imaging techniques taken 6-8 weeks after the last treatment. The recently validated Deauville 5-point scale was used to compare the differences between interim and final PET scans. This scale gauges the uptake of 18FDG within the tissues.
The minimum observation time was set at 2 years, unless a DLBCL event occurred earlier. Targeted biopsies were performed at the end of treatment if there was a mismatch between PET and CECT results, and at the interim stage if results were conflicting and the site in need of biopsy was easy to reach.
Almost two-thirds (62%) were biopsy negative. Dr. Cox noted that none of the interim PET, biopsy-negative patients relapsed.
At a median follow-up of almost 3 years, 70 (82.3%) patients were still alive, with 65 (76.4%) being disease free after first- or second-line therapy. One-fifth had been refractory to first-line treatment. Of these patients, 78% had a positive interim PET scan.
Looking at factors that might predict the achievement of a complete remission to first-line treatment, only the interim CECT results were statistically significant in a multivariate analysis (P less than .002).
In addition, only the final PET scan was predictive of both overall and progression-free survival, whereas interim and final CECT were both predictive.
"In this series, interim PET proved not to be a robust tool for the early shifting of patients to high-dose therapy," Dr. Cox reported. She added that compared with interim CECT and final PET, "interim PET was not really of adjunctive value." Indeed, most refractory patients (61%) were identified by interim CECT.
"We think that the use of this [interim PET] expensive, radioactive, and emotionally distressing tool is presently not justified outside of clinical trials."
Commenting on the findings in an interview, Dr. Andrew Pettitt, professor of hematological oncology at the University of Liverpool (England), said that although it was a good study, he was not convinced it was adequately powered to draw such a definitive conclusion. "I also have some reservations of the PET-CT reporting and quality control," Dr. Pettitt, who was not involved in the study. "It’s very provocative, but I don’t think it’s definitive."
Dr. Cox and Dr. Pettitt stated that they had no relevant financial disclosures.
R-CHOP, radiotherapy, 18FDG-PET, Dr. M. Christina Cox, the European Hematology Association,
R-CHOP, radiotherapy, 18FDG-PET, Dr. M. Christina Cox, the European Hematology Association,
FROM THE ANNUAL CONGRESS OF THE EUROPEAN HEMATOLOGY ASSOCIATION
Major Finding: Interim 18FDG-PET had a PPV of 58% and a NPV of 77%. By comparison, the values for 18FDG-PET performed 6-8 weeks after the last treatment cycle were 70% and 82%, respectively.
Data Source: Prospective study of 85 patients with DLBCL or PMLBCL enrolled over a 5-year period in 2005-2010.
Disclosures: Dr. Cox and Dr. Pettitt stated that they had no relevant disclosures.
Chemo Length May Not Affect Survival in Some B-cell Lymphomas
CHICAGO – It doesn’t seem to matter whether patients with newly diagnosed, diffuse large B-cell lymphoma receive a standard chemotherapy regimen in a dose-dense fashion every 14 days for six cycles, or every 21 days for eight cycles, said investigators in a multinational trial that was presented at the annual meeting of the American Society of Clinical Oncology.
There were no significant differences in the primary outcome of overall survival or the secondary outcome of failure-free survival among 1,080 patients who were randomly assigned to the two R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) regimens, reported Dr. David Cunningham of the Royal Marsden Hospital in London, on behalf of colleagues in the U.K. National Cancer Research Institute’s lymphoma clinical study group.
Half the population received R-CHOP every 3 weeks for eight cycles (R-CHOP-21), and the other half was assigned to R-CHOP every 2 weeks for six cycles, followed by two additional rituximab infusions (R-CHOP-14).
Dr. Cunningham highlighted the following findings:
• The 2-year overall survival rates were 81% in the R-CHOP-21 arm, and 83% in the R-CHOP-14 arm (log rank P = .70).
• Overall response rates (a combination of complete responses [CR], complete unconfirmed responses [CRu], and partial responses [PR]) were 88% in R-CHOP-21 and 90% in R-CHOP-14 (P = .11).
• Rates of combined CR/CRu were 63% and 58%, respectively (P = .15).
• The 2-year failure-free survival rates were identical, at 75% in each group.
Toxicities were also generally similar between the treatment groups, except for a lower incidence of neutropenia in the R-CHOP-14 arm, which reflected primary prophylaxis with granulocyte-colony-stimulating factor (G-CSF) in that group.
There were no differences in failure-free survival between the treatment arms when patients were stratified by age, sex, disease stage, bulky disease, B symptoms, prognostic score, IPI (International Prognostic Index) score, cell proliferation (as measured by the MIB-1 monoclonal antibody), or diffuse large B-cell lymphoma (DLBCL) phenotype.
"We couldn’t actually identify any of the subsets or subgroups that benefited from one or the other treatment," Dr. Cunningham said.
Dr. Julie Vose of the University of Nebraska Medical Center in Omaha, the invited discussant, commented that the study "compared some questions that have been burning in our minds for a long time," calling it a "very robust analysis of a very important study."
Summing up this study and three other abstracts that looked at alternative therapies for DLBCL, Dr. Vose said that R-CHOP-21 is still the standard of care for young patients with low, low/intermediate, or high/intermediate IPI scores, although R-CHOP-14 plus two rituximab infusions or R-CHOEP (R-CHOP plus etoposide) are acceptable alternatives. For young patients with high IPI, R-CHOP-21 followed by consolidation autologous transplant should be offered. For older patients, R-CHOP-21 for eight cycles is equivalent to R-CHOP-14 for six cycles plus two rituximab infusions.
The trial began recruiting after a 2004 German study showed that a dose-dense regimen of six cycles of CHOP-14 improved 5-year overall survival in patients older than 60 years by 13%, compared with six cycles of CHOP-21 (Blood 2004;104:634-41).
Since that publication, however, the addition of rituximab to six or eight cycles of CHOP or similar chemotherapy regimens was shown to improve overall survival of DLBCL by 10%-16% in two trials. Those findings raised interest in whether CHOP-14 might still be superior to CHOP-21 in patients who also receive rituximab, and whether such an effect would be seen across all age groups, Dr. Cunningham said.
He reported the final results of the trial, which involved 1,080 adults who had newly diagnosed CD20-positive DLBCL and were recruited from 119 sites. The patients were stratified by IPI score, age (60 years and younger, or older than 60), and treatment center.
In all, 23% of patients on R-CHOP-21 and 22% on R-CHOP-14 had died by the time of the final study analysis. DLBCL was the leading cause of death in both arms. Other causes included treatment-related toxicity, cardiac causes (all cardiac deaths occurred 3-15 months after completion of therapy), secondary malignancy, and other/unknown causes.
In her discussion, Dr. Vose pointed out that R-CHOP-14, which requires G-CSF support after every cycle, costs about $31,308, compared with $29,247 for R-CHOP-21, in which G-CSF is used only to treat (but not to prevent) neutropenia or febrile neutropenia. In the trial, G-CSF was used in 38% of R-CHOP-21 cycles, compared with 100% of R-CHOP-14 cycles.
In addition, R-CHOP every 21 days for six cycles (not eight) is generally considered to be the standard of care in the United States, she noted; a direct comparison of this shorter regimen with R-CHOP-14 would have been welcome, she said.
The trial was funded by the U.K. National Cancer Research Institute. The authors had no relevant financial disclosures.
CHICAGO – It doesn’t seem to matter whether patients with newly diagnosed, diffuse large B-cell lymphoma receive a standard chemotherapy regimen in a dose-dense fashion every 14 days for six cycles, or every 21 days for eight cycles, said investigators in a multinational trial that was presented at the annual meeting of the American Society of Clinical Oncology.
There were no significant differences in the primary outcome of overall survival or the secondary outcome of failure-free survival among 1,080 patients who were randomly assigned to the two R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) regimens, reported Dr. David Cunningham of the Royal Marsden Hospital in London, on behalf of colleagues in the U.K. National Cancer Research Institute’s lymphoma clinical study group.
Half the population received R-CHOP every 3 weeks for eight cycles (R-CHOP-21), and the other half was assigned to R-CHOP every 2 weeks for six cycles, followed by two additional rituximab infusions (R-CHOP-14).
Dr. Cunningham highlighted the following findings:
• The 2-year overall survival rates were 81% in the R-CHOP-21 arm, and 83% in the R-CHOP-14 arm (log rank P = .70).
• Overall response rates (a combination of complete responses [CR], complete unconfirmed responses [CRu], and partial responses [PR]) were 88% in R-CHOP-21 and 90% in R-CHOP-14 (P = .11).
• Rates of combined CR/CRu were 63% and 58%, respectively (P = .15).
• The 2-year failure-free survival rates were identical, at 75% in each group.
Toxicities were also generally similar between the treatment groups, except for a lower incidence of neutropenia in the R-CHOP-14 arm, which reflected primary prophylaxis with granulocyte-colony-stimulating factor (G-CSF) in that group.
There were no differences in failure-free survival between the treatment arms when patients were stratified by age, sex, disease stage, bulky disease, B symptoms, prognostic score, IPI (International Prognostic Index) score, cell proliferation (as measured by the MIB-1 monoclonal antibody), or diffuse large B-cell lymphoma (DLBCL) phenotype.
"We couldn’t actually identify any of the subsets or subgroups that benefited from one or the other treatment," Dr. Cunningham said.
Dr. Julie Vose of the University of Nebraska Medical Center in Omaha, the invited discussant, commented that the study "compared some questions that have been burning in our minds for a long time," calling it a "very robust analysis of a very important study."
Summing up this study and three other abstracts that looked at alternative therapies for DLBCL, Dr. Vose said that R-CHOP-21 is still the standard of care for young patients with low, low/intermediate, or high/intermediate IPI scores, although R-CHOP-14 plus two rituximab infusions or R-CHOEP (R-CHOP plus etoposide) are acceptable alternatives. For young patients with high IPI, R-CHOP-21 followed by consolidation autologous transplant should be offered. For older patients, R-CHOP-21 for eight cycles is equivalent to R-CHOP-14 for six cycles plus two rituximab infusions.
The trial began recruiting after a 2004 German study showed that a dose-dense regimen of six cycles of CHOP-14 improved 5-year overall survival in patients older than 60 years by 13%, compared with six cycles of CHOP-21 (Blood 2004;104:634-41).
Since that publication, however, the addition of rituximab to six or eight cycles of CHOP or similar chemotherapy regimens was shown to improve overall survival of DLBCL by 10%-16% in two trials. Those findings raised interest in whether CHOP-14 might still be superior to CHOP-21 in patients who also receive rituximab, and whether such an effect would be seen across all age groups, Dr. Cunningham said.
He reported the final results of the trial, which involved 1,080 adults who had newly diagnosed CD20-positive DLBCL and were recruited from 119 sites. The patients were stratified by IPI score, age (60 years and younger, or older than 60), and treatment center.
In all, 23% of patients on R-CHOP-21 and 22% on R-CHOP-14 had died by the time of the final study analysis. DLBCL was the leading cause of death in both arms. Other causes included treatment-related toxicity, cardiac causes (all cardiac deaths occurred 3-15 months after completion of therapy), secondary malignancy, and other/unknown causes.
In her discussion, Dr. Vose pointed out that R-CHOP-14, which requires G-CSF support after every cycle, costs about $31,308, compared with $29,247 for R-CHOP-21, in which G-CSF is used only to treat (but not to prevent) neutropenia or febrile neutropenia. In the trial, G-CSF was used in 38% of R-CHOP-21 cycles, compared with 100% of R-CHOP-14 cycles.
In addition, R-CHOP every 21 days for six cycles (not eight) is generally considered to be the standard of care in the United States, she noted; a direct comparison of this shorter regimen with R-CHOP-14 would have been welcome, she said.
The trial was funded by the U.K. National Cancer Research Institute. The authors had no relevant financial disclosures.
CHICAGO – It doesn’t seem to matter whether patients with newly diagnosed, diffuse large B-cell lymphoma receive a standard chemotherapy regimen in a dose-dense fashion every 14 days for six cycles, or every 21 days for eight cycles, said investigators in a multinational trial that was presented at the annual meeting of the American Society of Clinical Oncology.
There were no significant differences in the primary outcome of overall survival or the secondary outcome of failure-free survival among 1,080 patients who were randomly assigned to the two R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) regimens, reported Dr. David Cunningham of the Royal Marsden Hospital in London, on behalf of colleagues in the U.K. National Cancer Research Institute’s lymphoma clinical study group.
Half the population received R-CHOP every 3 weeks for eight cycles (R-CHOP-21), and the other half was assigned to R-CHOP every 2 weeks for six cycles, followed by two additional rituximab infusions (R-CHOP-14).
Dr. Cunningham highlighted the following findings:
• The 2-year overall survival rates were 81% in the R-CHOP-21 arm, and 83% in the R-CHOP-14 arm (log rank P = .70).
• Overall response rates (a combination of complete responses [CR], complete unconfirmed responses [CRu], and partial responses [PR]) were 88% in R-CHOP-21 and 90% in R-CHOP-14 (P = .11).
• Rates of combined CR/CRu were 63% and 58%, respectively (P = .15).
• The 2-year failure-free survival rates were identical, at 75% in each group.
Toxicities were also generally similar between the treatment groups, except for a lower incidence of neutropenia in the R-CHOP-14 arm, which reflected primary prophylaxis with granulocyte-colony-stimulating factor (G-CSF) in that group.
There were no differences in failure-free survival between the treatment arms when patients were stratified by age, sex, disease stage, bulky disease, B symptoms, prognostic score, IPI (International Prognostic Index) score, cell proliferation (as measured by the MIB-1 monoclonal antibody), or diffuse large B-cell lymphoma (DLBCL) phenotype.
"We couldn’t actually identify any of the subsets or subgroups that benefited from one or the other treatment," Dr. Cunningham said.
Dr. Julie Vose of the University of Nebraska Medical Center in Omaha, the invited discussant, commented that the study "compared some questions that have been burning in our minds for a long time," calling it a "very robust analysis of a very important study."
Summing up this study and three other abstracts that looked at alternative therapies for DLBCL, Dr. Vose said that R-CHOP-21 is still the standard of care for young patients with low, low/intermediate, or high/intermediate IPI scores, although R-CHOP-14 plus two rituximab infusions or R-CHOEP (R-CHOP plus etoposide) are acceptable alternatives. For young patients with high IPI, R-CHOP-21 followed by consolidation autologous transplant should be offered. For older patients, R-CHOP-21 for eight cycles is equivalent to R-CHOP-14 for six cycles plus two rituximab infusions.
The trial began recruiting after a 2004 German study showed that a dose-dense regimen of six cycles of CHOP-14 improved 5-year overall survival in patients older than 60 years by 13%, compared with six cycles of CHOP-21 (Blood 2004;104:634-41).
Since that publication, however, the addition of rituximab to six or eight cycles of CHOP or similar chemotherapy regimens was shown to improve overall survival of DLBCL by 10%-16% in two trials. Those findings raised interest in whether CHOP-14 might still be superior to CHOP-21 in patients who also receive rituximab, and whether such an effect would be seen across all age groups, Dr. Cunningham said.
He reported the final results of the trial, which involved 1,080 adults who had newly diagnosed CD20-positive DLBCL and were recruited from 119 sites. The patients were stratified by IPI score, age (60 years and younger, or older than 60), and treatment center.
In all, 23% of patients on R-CHOP-21 and 22% on R-CHOP-14 had died by the time of the final study analysis. DLBCL was the leading cause of death in both arms. Other causes included treatment-related toxicity, cardiac causes (all cardiac deaths occurred 3-15 months after completion of therapy), secondary malignancy, and other/unknown causes.
In her discussion, Dr. Vose pointed out that R-CHOP-14, which requires G-CSF support after every cycle, costs about $31,308, compared with $29,247 for R-CHOP-21, in which G-CSF is used only to treat (but not to prevent) neutropenia or febrile neutropenia. In the trial, G-CSF was used in 38% of R-CHOP-21 cycles, compared with 100% of R-CHOP-14 cycles.
In addition, R-CHOP every 21 days for six cycles (not eight) is generally considered to be the standard of care in the United States, she noted; a direct comparison of this shorter regimen with R-CHOP-14 would have been welcome, she said.
The trial was funded by the U.K. National Cancer Research Institute. The authors had no relevant financial disclosures.
FROM THE ANNUAL MEETING OF THE AMERICAN SOCIETY OF CLINICAL ONCOLOGY
Major Finding: The 2-year overall survival rates were 81% in the R-CHOP-21 arm, and 83% in the R-CHOP-14 arm (log rank P = .70).
Data Source: Final analysis of a randomized controlled trial in 1,080 newly diagnosed patients with diffuse, large B-cell lymphomas.
Disclosures: The trial was funded by the U.K. National Cancer Research Institute. The authors had no relevant financial disclosures.