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Patients with acute myeloid leukemia (AML) who are in remission but with minimal residual disease (MRD) detectable by multiparameter flow cytometry have outcomes similar to those of patients with morphologically detectable disease, and both groups have significantly worse outcomes than patients in MRD-negative remission.
“Is it time to move toward an MRD-based definition of CR [complete remission]? We believe so,” wrote Dr. Daisuke Araki of the University of Washington, Seattle, and colleagues. The researchers suggest that decision algorithms based on “the classic morphologic remission definition are not ideal. Our data support treatment algorithms that use MRD-based (i.e., patients in MRD-negative CR [versus] all other patients), rather than morphology-based disease assessments” (J Clin Oncol. 2015 Dec 12 [doi:10.1200/JCO.2015.63.3826]).
Three-year overall survival estimates for patients with active AML, patients in MRD-positive remission, and patients in MRD-negative remission were 23% (12%-35%), 26% (17%-37%), and 73% (66%-78%), respectively. Progression-free survival estimates showed a similar delineation between patients with morphologically detectable AML and MRD-positive remission compared with MRD-negative remission: 13% (5%-23%) for active AML, 12% (5%-21%) for MRD-positive remission, and 67% (61%-73%) for MRD-negative remission.
The retrospective analysis included 359 patients with AML treated with myeloablative hematopoietic cell transplantation (HCT) at the Fred Hutchinson Cancer Research Center from 2006 to 2014. In total, 311 patients (87%) had morphologically determined CR (less than 5% bone marrow blasts). Of these, 76 patients (24%) had MRD by multiparameter flow cytometry (MRD-positive remission) and 235 (76%) had no flow cytometric evidence of MRD (MRD-negative remission). In the pre-HCT assessment, 48 patients (13%) had 5% or more bone marrow blasts and were classified as having active AML.
Even patients with the lowest detectable amount of MRD had significantly worse outcomes than did patients with no MRD. Among the patients with evidence of leukemia (those in MRD-positive remission and with classified active AML), researchers found no statistically significant differences in outcomes based on MRD levels (less than 0.5%, 0.5%-5%, and greater than 5% abnormal blasts). Sensitivity analysis with different cut points yielded similar findings.
However, in line with previous findings, the data show that a small but significant subset of patients with active leukemia at the time of HCT can achieve long-term disease control with myeloablative conditioning.
No significant associations were found between disease status and non-relapse mortality.
The investigators caution that the results do not necessarily demonstrate that HCT outcomes for patients in MRD-positive remission and those with active disease are identical, because the preparative regimens, in general, were different for the two groups.
Dr. Araki reported having no disclosures. Several of his coauthors reported ties to industry.
For patients in complete remission, with a risk profile that suggests HCT to cure acute myeloid leukemia, MRD should not be ignored. The inexpensive, relatively easy-to-assess analysis provides a sensitive and patient-specific risk indicator, adding information beyond cytogenetic risk class and underlying genetic abnormalities. The results from Araki et al. prompt new clinical studies and, perhaps, a new transplantation strategy. Patients in MRD-positive remission could be combined with patients with active disease in trials aimed primarily at reducing the risk of post-transplant relapse.
In acute lymphoblastic leukemia (ALL), MRD refines individual risk assessment and is crucial to decision making regarding HCT. Its role in AML is similarly growing in importance.
HCT is a powerful therapy commonly prescribed for younger patients in CR with intermediate- and high-risk characteristics, but has significant downsides in terms of economic costs, acute and chronic toxicities, and above all, risk of transplant-related mortality, which averages just below 10%. Use of MRD may profoundly influence the treatment approach for AML by permitting a better definition of CR and risk class, and favoring better risk-adapted treatment strategies oriented to spared the risk of treatment-related mortality and transplant-related morbidity.
One additional note concerns the potential bias in positive results for successful late transplantation in MRD-negative patients (after 6-12 months from CR). Some of these patients may have been cured by prior chemotherapy, particularly if a patient tests negative for MRD soon after achieving CR and prior to HCT. New trials should address this bias by using predefined MRD time points from CR to HCT.
Dr. Renato Bassan is an oncologist at UOC Ematologia, Ospedale dell’Angelo, Mestre-Venezia, Italy. These remarks were part of an editorial accompanying a report in the Journal of Clinical Oncology (2015 Dec 12. doi: 10.1200/JCO.2015.64.8907). Dr. Bassan reported ties to Mundipharma, ARIAD, Roche, and Amgen.
For patients in complete remission, with a risk profile that suggests HCT to cure acute myeloid leukemia, MRD should not be ignored. The inexpensive, relatively easy-to-assess analysis provides a sensitive and patient-specific risk indicator, adding information beyond cytogenetic risk class and underlying genetic abnormalities. The results from Araki et al. prompt new clinical studies and, perhaps, a new transplantation strategy. Patients in MRD-positive remission could be combined with patients with active disease in trials aimed primarily at reducing the risk of post-transplant relapse.
In acute lymphoblastic leukemia (ALL), MRD refines individual risk assessment and is crucial to decision making regarding HCT. Its role in AML is similarly growing in importance.
HCT is a powerful therapy commonly prescribed for younger patients in CR with intermediate- and high-risk characteristics, but has significant downsides in terms of economic costs, acute and chronic toxicities, and above all, risk of transplant-related mortality, which averages just below 10%. Use of MRD may profoundly influence the treatment approach for AML by permitting a better definition of CR and risk class, and favoring better risk-adapted treatment strategies oriented to spared the risk of treatment-related mortality and transplant-related morbidity.
One additional note concerns the potential bias in positive results for successful late transplantation in MRD-negative patients (after 6-12 months from CR). Some of these patients may have been cured by prior chemotherapy, particularly if a patient tests negative for MRD soon after achieving CR and prior to HCT. New trials should address this bias by using predefined MRD time points from CR to HCT.
Dr. Renato Bassan is an oncologist at UOC Ematologia, Ospedale dell’Angelo, Mestre-Venezia, Italy. These remarks were part of an editorial accompanying a report in the Journal of Clinical Oncology (2015 Dec 12. doi: 10.1200/JCO.2015.64.8907). Dr. Bassan reported ties to Mundipharma, ARIAD, Roche, and Amgen.
For patients in complete remission, with a risk profile that suggests HCT to cure acute myeloid leukemia, MRD should not be ignored. The inexpensive, relatively easy-to-assess analysis provides a sensitive and patient-specific risk indicator, adding information beyond cytogenetic risk class and underlying genetic abnormalities. The results from Araki et al. prompt new clinical studies and, perhaps, a new transplantation strategy. Patients in MRD-positive remission could be combined with patients with active disease in trials aimed primarily at reducing the risk of post-transplant relapse.
In acute lymphoblastic leukemia (ALL), MRD refines individual risk assessment and is crucial to decision making regarding HCT. Its role in AML is similarly growing in importance.
HCT is a powerful therapy commonly prescribed for younger patients in CR with intermediate- and high-risk characteristics, but has significant downsides in terms of economic costs, acute and chronic toxicities, and above all, risk of transplant-related mortality, which averages just below 10%. Use of MRD may profoundly influence the treatment approach for AML by permitting a better definition of CR and risk class, and favoring better risk-adapted treatment strategies oriented to spared the risk of treatment-related mortality and transplant-related morbidity.
One additional note concerns the potential bias in positive results for successful late transplantation in MRD-negative patients (after 6-12 months from CR). Some of these patients may have been cured by prior chemotherapy, particularly if a patient tests negative for MRD soon after achieving CR and prior to HCT. New trials should address this bias by using predefined MRD time points from CR to HCT.
Dr. Renato Bassan is an oncologist at UOC Ematologia, Ospedale dell’Angelo, Mestre-Venezia, Italy. These remarks were part of an editorial accompanying a report in the Journal of Clinical Oncology (2015 Dec 12. doi: 10.1200/JCO.2015.64.8907). Dr. Bassan reported ties to Mundipharma, ARIAD, Roche, and Amgen.
Patients with acute myeloid leukemia (AML) who are in remission but with minimal residual disease (MRD) detectable by multiparameter flow cytometry have outcomes similar to those of patients with morphologically detectable disease, and both groups have significantly worse outcomes than patients in MRD-negative remission.
“Is it time to move toward an MRD-based definition of CR [complete remission]? We believe so,” wrote Dr. Daisuke Araki of the University of Washington, Seattle, and colleagues. The researchers suggest that decision algorithms based on “the classic morphologic remission definition are not ideal. Our data support treatment algorithms that use MRD-based (i.e., patients in MRD-negative CR [versus] all other patients), rather than morphology-based disease assessments” (J Clin Oncol. 2015 Dec 12 [doi:10.1200/JCO.2015.63.3826]).
Three-year overall survival estimates for patients with active AML, patients in MRD-positive remission, and patients in MRD-negative remission were 23% (12%-35%), 26% (17%-37%), and 73% (66%-78%), respectively. Progression-free survival estimates showed a similar delineation between patients with morphologically detectable AML and MRD-positive remission compared with MRD-negative remission: 13% (5%-23%) for active AML, 12% (5%-21%) for MRD-positive remission, and 67% (61%-73%) for MRD-negative remission.
The retrospective analysis included 359 patients with AML treated with myeloablative hematopoietic cell transplantation (HCT) at the Fred Hutchinson Cancer Research Center from 2006 to 2014. In total, 311 patients (87%) had morphologically determined CR (less than 5% bone marrow blasts). Of these, 76 patients (24%) had MRD by multiparameter flow cytometry (MRD-positive remission) and 235 (76%) had no flow cytometric evidence of MRD (MRD-negative remission). In the pre-HCT assessment, 48 patients (13%) had 5% or more bone marrow blasts and were classified as having active AML.
Even patients with the lowest detectable amount of MRD had significantly worse outcomes than did patients with no MRD. Among the patients with evidence of leukemia (those in MRD-positive remission and with classified active AML), researchers found no statistically significant differences in outcomes based on MRD levels (less than 0.5%, 0.5%-5%, and greater than 5% abnormal blasts). Sensitivity analysis with different cut points yielded similar findings.
However, in line with previous findings, the data show that a small but significant subset of patients with active leukemia at the time of HCT can achieve long-term disease control with myeloablative conditioning.
No significant associations were found between disease status and non-relapse mortality.
The investigators caution that the results do not necessarily demonstrate that HCT outcomes for patients in MRD-positive remission and those with active disease are identical, because the preparative regimens, in general, were different for the two groups.
Dr. Araki reported having no disclosures. Several of his coauthors reported ties to industry.
Patients with acute myeloid leukemia (AML) who are in remission but with minimal residual disease (MRD) detectable by multiparameter flow cytometry have outcomes similar to those of patients with morphologically detectable disease, and both groups have significantly worse outcomes than patients in MRD-negative remission.
“Is it time to move toward an MRD-based definition of CR [complete remission]? We believe so,” wrote Dr. Daisuke Araki of the University of Washington, Seattle, and colleagues. The researchers suggest that decision algorithms based on “the classic morphologic remission definition are not ideal. Our data support treatment algorithms that use MRD-based (i.e., patients in MRD-negative CR [versus] all other patients), rather than morphology-based disease assessments” (J Clin Oncol. 2015 Dec 12 [doi:10.1200/JCO.2015.63.3826]).
Three-year overall survival estimates for patients with active AML, patients in MRD-positive remission, and patients in MRD-negative remission were 23% (12%-35%), 26% (17%-37%), and 73% (66%-78%), respectively. Progression-free survival estimates showed a similar delineation between patients with morphologically detectable AML and MRD-positive remission compared with MRD-negative remission: 13% (5%-23%) for active AML, 12% (5%-21%) for MRD-positive remission, and 67% (61%-73%) for MRD-negative remission.
The retrospective analysis included 359 patients with AML treated with myeloablative hematopoietic cell transplantation (HCT) at the Fred Hutchinson Cancer Research Center from 2006 to 2014. In total, 311 patients (87%) had morphologically determined CR (less than 5% bone marrow blasts). Of these, 76 patients (24%) had MRD by multiparameter flow cytometry (MRD-positive remission) and 235 (76%) had no flow cytometric evidence of MRD (MRD-negative remission). In the pre-HCT assessment, 48 patients (13%) had 5% or more bone marrow blasts and were classified as having active AML.
Even patients with the lowest detectable amount of MRD had significantly worse outcomes than did patients with no MRD. Among the patients with evidence of leukemia (those in MRD-positive remission and with classified active AML), researchers found no statistically significant differences in outcomes based on MRD levels (less than 0.5%, 0.5%-5%, and greater than 5% abnormal blasts). Sensitivity analysis with different cut points yielded similar findings.
However, in line with previous findings, the data show that a small but significant subset of patients with active leukemia at the time of HCT can achieve long-term disease control with myeloablative conditioning.
No significant associations were found between disease status and non-relapse mortality.
The investigators caution that the results do not necessarily demonstrate that HCT outcomes for patients in MRD-positive remission and those with active disease are identical, because the preparative regimens, in general, were different for the two groups.
Dr. Araki reported having no disclosures. Several of his coauthors reported ties to industry.
Key clinical point: Allogeneic hematopoietic cell transplantation (HCT) outcomes for patients in minimal residual disease (MRD)–positive remission were similar to outcomes of patients with morphologically detectable acute myeloid leukemia (AML), and significantly worse than outcomes of patients in MRD-negative remission.
Major finding: Three-year overall survival estimates for patients with active AML, patients in MRD-positive remission, and patients in MRD-negative remission were 23% (12%-35%), 26% (17%-37%), and 73% (66%-78%), respectively.
Data sources: A retrospective analysis of 359 patients with AML treated with myeloablative HCT at the Fred Hutchinson Cancer Research Center from 2006 to 2014.
Disclosures: Dr. Araki reported having no disclosures. Several of his coauthors reported ties to industry.