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For patients with follicular lymphoma treated with a rituximab-based combination chemotherapy regimen, early disease progression is associated with significantly worse overall survival, suggesting the need for additional interventions, according to results of a multicenter study.
Among 588 patients with stage 2-4 follicular lymphoma treated with first-line R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) and followed for a median of 7 years in the National LymphoCare Study, overall survival (OS) at 2 years was 68% for those who had disease progression within 2 years, compared with 97% for patients with no disease progression during that time.
Similarly, 5-year overall survival was 50% for patients with early progression of disease, compared with 90% for patients with no early progression, write Dr. Carla Casulo of the University of Rochester (N.Y.) Medical Center and colleagues. The study is in anearly online publication in the Journal of Clinical Oncology.
“Given our findings, early relapse after diagnosis in patients treated with first-line chemoimmunotherapy is a powerful prognostic indicator of outcome and should be used to stratify the risk of patients in studies of relapsed follicular lymphoma,” the authors wrote.
The findings were validated in an independent cohort of patients with follicular lymphoma treated with R-CHOP from the University of Iowa and Mayo Clinical Molecular Epidemiology Resource, and are consistent with findings from other studies of patients treated with different rituximab-based regimens, the investigators reported.
In unadjusted analysis, early disease progression was associated with a hazard ratio (HR) of 7.17 (95% confidence interval [CI] 4.83-10.65); the effect remained after adjustment for the Follicular Lymphoma International Prognostic Index (FLIPI) score (HR 6.44, 95% CI, 4.33-9.58).
Factors associated with early progression included age, Eastern Cooperative Oncology Group performance score, nodal sites, and disease stage.
Early use of aggressive salvage therapies or autologous stem-cell transplantation could improve outcomes in patients with early disease progression, the authors wrote. However, only 8 patients among the 110 with early progression went on to transplant, not a large enough sample for meaningful analysis, they added.
“This newly defined high-risk group of patients represents a distinct population in whom further study is warranted in both directed prospective clinical trials of follicular lymphoma biology and treatment. Moreover, we propose that 2-year progression-free survival may be a practical and meaningful clinical end point for trials involving a chemoimmunotherapy backbone,” they concluded.
If, in studying the immunologic and inflammatory host response to, and the genetic landscape of, these lymphomas, we are able to define this high-risk subgroup of patients with follicular lymphoma, the question becomes whether we could use this information to effectively treat these patients differently. Although high-dose chemotherapy and autologous stem-cell transplantation (HDC-ASCT) in first remission seems to have no effect on OS in all comers, results might be different for this cohort of high-risk patients. To study this would require an ability to identify these patients at diagnosis. Given that the efficacy of HDC-ASCT is maintained in the case of chemosensitive relapse, reserving HDC-ASCT for patients who relapse within the first 2 years of their initial therapy may be a more prudent strategy.
However, it may be that this is a particularly chemoresistant population and that, instead, attention should be paid to targeting the biologic and genetic factors that contribute to the poor prognosis of this group. Given the negative differential outcomes in patients with decreased tumor-infiltrating lymphocytes and increased monocyte/macrophage activation, immunologic approaches in the salvage setting, including immune checkpoint blockade drugs, chimeric antigen receptor T cells, and allogeneic transplantation may be biologically relevant.
Dr. Caron A. Jacobson and Dr. Arnold S. Freedman, of the Dana-Farber Cancer Institute and Harvard Medical School, Boston, made their remarks in an editorial accompanying the study.
If, in studying the immunologic and inflammatory host response to, and the genetic landscape of, these lymphomas, we are able to define this high-risk subgroup of patients with follicular lymphoma, the question becomes whether we could use this information to effectively treat these patients differently. Although high-dose chemotherapy and autologous stem-cell transplantation (HDC-ASCT) in first remission seems to have no effect on OS in all comers, results might be different for this cohort of high-risk patients. To study this would require an ability to identify these patients at diagnosis. Given that the efficacy of HDC-ASCT is maintained in the case of chemosensitive relapse, reserving HDC-ASCT for patients who relapse within the first 2 years of their initial therapy may be a more prudent strategy.
However, it may be that this is a particularly chemoresistant population and that, instead, attention should be paid to targeting the biologic and genetic factors that contribute to the poor prognosis of this group. Given the negative differential outcomes in patients with decreased tumor-infiltrating lymphocytes and increased monocyte/macrophage activation, immunologic approaches in the salvage setting, including immune checkpoint blockade drugs, chimeric antigen receptor T cells, and allogeneic transplantation may be biologically relevant.
Dr. Caron A. Jacobson and Dr. Arnold S. Freedman, of the Dana-Farber Cancer Institute and Harvard Medical School, Boston, made their remarks in an editorial accompanying the study.
If, in studying the immunologic and inflammatory host response to, and the genetic landscape of, these lymphomas, we are able to define this high-risk subgroup of patients with follicular lymphoma, the question becomes whether we could use this information to effectively treat these patients differently. Although high-dose chemotherapy and autologous stem-cell transplantation (HDC-ASCT) in first remission seems to have no effect on OS in all comers, results might be different for this cohort of high-risk patients. To study this would require an ability to identify these patients at diagnosis. Given that the efficacy of HDC-ASCT is maintained in the case of chemosensitive relapse, reserving HDC-ASCT for patients who relapse within the first 2 years of their initial therapy may be a more prudent strategy.
However, it may be that this is a particularly chemoresistant population and that, instead, attention should be paid to targeting the biologic and genetic factors that contribute to the poor prognosis of this group. Given the negative differential outcomes in patients with decreased tumor-infiltrating lymphocytes and increased monocyte/macrophage activation, immunologic approaches in the salvage setting, including immune checkpoint blockade drugs, chimeric antigen receptor T cells, and allogeneic transplantation may be biologically relevant.
Dr. Caron A. Jacobson and Dr. Arnold S. Freedman, of the Dana-Farber Cancer Institute and Harvard Medical School, Boston, made their remarks in an editorial accompanying the study.
For patients with follicular lymphoma treated with a rituximab-based combination chemotherapy regimen, early disease progression is associated with significantly worse overall survival, suggesting the need for additional interventions, according to results of a multicenter study.
Among 588 patients with stage 2-4 follicular lymphoma treated with first-line R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) and followed for a median of 7 years in the National LymphoCare Study, overall survival (OS) at 2 years was 68% for those who had disease progression within 2 years, compared with 97% for patients with no disease progression during that time.
Similarly, 5-year overall survival was 50% for patients with early progression of disease, compared with 90% for patients with no early progression, write Dr. Carla Casulo of the University of Rochester (N.Y.) Medical Center and colleagues. The study is in anearly online publication in the Journal of Clinical Oncology.
“Given our findings, early relapse after diagnosis in patients treated with first-line chemoimmunotherapy is a powerful prognostic indicator of outcome and should be used to stratify the risk of patients in studies of relapsed follicular lymphoma,” the authors wrote.
The findings were validated in an independent cohort of patients with follicular lymphoma treated with R-CHOP from the University of Iowa and Mayo Clinical Molecular Epidemiology Resource, and are consistent with findings from other studies of patients treated with different rituximab-based regimens, the investigators reported.
In unadjusted analysis, early disease progression was associated with a hazard ratio (HR) of 7.17 (95% confidence interval [CI] 4.83-10.65); the effect remained after adjustment for the Follicular Lymphoma International Prognostic Index (FLIPI) score (HR 6.44, 95% CI, 4.33-9.58).
Factors associated with early progression included age, Eastern Cooperative Oncology Group performance score, nodal sites, and disease stage.
Early use of aggressive salvage therapies or autologous stem-cell transplantation could improve outcomes in patients with early disease progression, the authors wrote. However, only 8 patients among the 110 with early progression went on to transplant, not a large enough sample for meaningful analysis, they added.
“This newly defined high-risk group of patients represents a distinct population in whom further study is warranted in both directed prospective clinical trials of follicular lymphoma biology and treatment. Moreover, we propose that 2-year progression-free survival may be a practical and meaningful clinical end point for trials involving a chemoimmunotherapy backbone,” they concluded.
For patients with follicular lymphoma treated with a rituximab-based combination chemotherapy regimen, early disease progression is associated with significantly worse overall survival, suggesting the need for additional interventions, according to results of a multicenter study.
Among 588 patients with stage 2-4 follicular lymphoma treated with first-line R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) and followed for a median of 7 years in the National LymphoCare Study, overall survival (OS) at 2 years was 68% for those who had disease progression within 2 years, compared with 97% for patients with no disease progression during that time.
Similarly, 5-year overall survival was 50% for patients with early progression of disease, compared with 90% for patients with no early progression, write Dr. Carla Casulo of the University of Rochester (N.Y.) Medical Center and colleagues. The study is in anearly online publication in the Journal of Clinical Oncology.
“Given our findings, early relapse after diagnosis in patients treated with first-line chemoimmunotherapy is a powerful prognostic indicator of outcome and should be used to stratify the risk of patients in studies of relapsed follicular lymphoma,” the authors wrote.
The findings were validated in an independent cohort of patients with follicular lymphoma treated with R-CHOP from the University of Iowa and Mayo Clinical Molecular Epidemiology Resource, and are consistent with findings from other studies of patients treated with different rituximab-based regimens, the investigators reported.
In unadjusted analysis, early disease progression was associated with a hazard ratio (HR) of 7.17 (95% confidence interval [CI] 4.83-10.65); the effect remained after adjustment for the Follicular Lymphoma International Prognostic Index (FLIPI) score (HR 6.44, 95% CI, 4.33-9.58).
Factors associated with early progression included age, Eastern Cooperative Oncology Group performance score, nodal sites, and disease stage.
Early use of aggressive salvage therapies or autologous stem-cell transplantation could improve outcomes in patients with early disease progression, the authors wrote. However, only 8 patients among the 110 with early progression went on to transplant, not a large enough sample for meaningful analysis, they added.
“This newly defined high-risk group of patients represents a distinct population in whom further study is warranted in both directed prospective clinical trials of follicular lymphoma biology and treatment. Moreover, we propose that 2-year progression-free survival may be a practical and meaningful clinical end point for trials involving a chemoimmunotherapy backbone,” they concluded.
FROM JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: Disease progression within 2 years of chemotherapy for follicular lymphoma is associated with poor outcomes.
Major finding: Five-year overall survival was 50% for patients with follicular lymphoma with disease progression within 2-years of R-CHOP, vs. 90% for patients with no early progression.
Data source: Retrospective review involving 588 patients in the longitudinal National LymphoCare Study.
Disclosures: Genentech and F. Hoffmann-La Roche supported the study. Dr. Casulo and Dr. Jacobson reported no relevant disclosures. Dr. Freedman reported ties with UpToDate, Axio, and Immunogen.
