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according to the results of a single-arm phase 2 study.
After a median follow-up of 29 months, 2-year progression-free survival was 59% with a median of 25 months for 52 patients with newly diagnosed disease who were aged 60 years or older, Hagop Kantarjian, MD, and his associates reported online in the Lancet Oncology.
Nearly every patient experienced an overall response (98%). The treatment also appeared to be safe, Dr. Kantarjian and associates wrote.
They reported that no patient died within 4 weeks of treatment and that four patients experienced veno-occlusive disease. Common grade 3 or 4 side effects included thrombocytopenia (81%), consolidation chemotherapy (69%), hyperglycemia (54%), infections during induction (52%), hypokalemia (31%), increased aminotransferases (19%), hyperbilirubinemia (17%), and hemorrhage (15%). Six patients died from treatment-related side effects, five of whom died from sepsis and one of whom died as a result of veno-occlusive disease.
Inotuzumab ozogamicin is an anti-CD22 monoclonal antibody that is bound to the toxin calicheamicin. It has shown “substantial improvements” for some patient subgroups when added to hyper-CVAD chemotherapy (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with methotrexate and high-dose cytarabine); however, older patients have yet to experience a similar benefit, Dr. Kantarjian and his associates said.
Both CVAD and inotuzumab ozogamicin have shown to be quite toxic for older patients. So – in order limit increased toxicity – Dr. Kantarjian and his associates lowered the intensity of hyper-CVAD. They accomplished this by reducing some aspects of the regimen by up to 50% and eliminating anthracyclines altogether. The researchers referred to this regimen as “mini–hyper-CVD.” The mini–hyper-CVD did not appear to impact activity.
“In our study, activity did not appear to be compromised by the use of lower-intensity chemotherapy in combination with a novel monoclonal antibody,” they wrote.
Dr. Kantarjian and his associates noted that, while they observed fewer deaths compared with previously published data, the number of deaths they did observe in patients who achieved a complete response was high.
They suggested that modifications to the regimen could further improve safety and that such modifications required further research.
For the time being, however, the researchers noted that this low-intensity regimen, in combination in inotuzumab ozogamicin, is highly effective and that these data now require prospective confirmation in a randomized, phase 3 setting.
The study was funded by the MD Anderson Cancer Center. Researchers reported that Pfizer provided inotuzumab ozogamicin free of charge and that Dr. Kantarjian and two other researchers received grants from Pfizer.
SOURCE: Kantarjian H et al. Lancet Oncol. 2018 Jan 15. doi: 10.1016/S1470-2945(18)30011-1.
The efficacy and safety of inotuzumab ozogamicin reported by Hagop Kantarjian, MD, and his colleagues are an encouraging building block for older patents with acute lymphoblastic leukemia, according to Carmelo Rizzari, MD.
“The authors have upgraded the valuable premises available from early inotuzumab ozogamicin studies into more concrete promises by rationally integrating the drug in a reduced-intensity chemotherapy regimen,” wrote Dr. Rizzari in an accompanying editorial published Lancet Oncology.
Adding inotuzumab ozogamicin to chemotherapy has shown efficacy and safety for both pediatric and adult patients with relapsed or refractory acute lymphoblastic leukemia and therefore deserves more investigation in the “neglected” subgroup of older patients, according to Dr. Rizzari.
“Monoclonal antibodies represent, in the wider settings of immunotherapy, viable options to improve the results obtained in different subsets of patients with acute lymphoblastic leukemia,” wrote Dr. Rizzari.
Echoing the researchers, Dr. Rizzari mentioned the importance of the next step – a phase 3 trial comparing inotuzumab ozogamicin with the current standard of care – but also mentioned that a specific, widely recognized standard of care for this patient subgroup is difficult to pin down.
Dr. Rizzari is with the Pediatric Hematology-Oncology Unit of the University of Milano-Bicocca in Milan. These comments are based on an accompanying editorial published online in Lancet Oncology (2018 Jan 15. doi: 10.1016/S1470-2045[18]30013-5 ). Dr. Rizzari declared no competing interests.
The efficacy and safety of inotuzumab ozogamicin reported by Hagop Kantarjian, MD, and his colleagues are an encouraging building block for older patents with acute lymphoblastic leukemia, according to Carmelo Rizzari, MD.
“The authors have upgraded the valuable premises available from early inotuzumab ozogamicin studies into more concrete promises by rationally integrating the drug in a reduced-intensity chemotherapy regimen,” wrote Dr. Rizzari in an accompanying editorial published Lancet Oncology.
Adding inotuzumab ozogamicin to chemotherapy has shown efficacy and safety for both pediatric and adult patients with relapsed or refractory acute lymphoblastic leukemia and therefore deserves more investigation in the “neglected” subgroup of older patients, according to Dr. Rizzari.
“Monoclonal antibodies represent, in the wider settings of immunotherapy, viable options to improve the results obtained in different subsets of patients with acute lymphoblastic leukemia,” wrote Dr. Rizzari.
Echoing the researchers, Dr. Rizzari mentioned the importance of the next step – a phase 3 trial comparing inotuzumab ozogamicin with the current standard of care – but also mentioned that a specific, widely recognized standard of care for this patient subgroup is difficult to pin down.
Dr. Rizzari is with the Pediatric Hematology-Oncology Unit of the University of Milano-Bicocca in Milan. These comments are based on an accompanying editorial published online in Lancet Oncology (2018 Jan 15. doi: 10.1016/S1470-2045[18]30013-5 ). Dr. Rizzari declared no competing interests.
The efficacy and safety of inotuzumab ozogamicin reported by Hagop Kantarjian, MD, and his colleagues are an encouraging building block for older patents with acute lymphoblastic leukemia, according to Carmelo Rizzari, MD.
“The authors have upgraded the valuable premises available from early inotuzumab ozogamicin studies into more concrete promises by rationally integrating the drug in a reduced-intensity chemotherapy regimen,” wrote Dr. Rizzari in an accompanying editorial published Lancet Oncology.
Adding inotuzumab ozogamicin to chemotherapy has shown efficacy and safety for both pediatric and adult patients with relapsed or refractory acute lymphoblastic leukemia and therefore deserves more investigation in the “neglected” subgroup of older patients, according to Dr. Rizzari.
“Monoclonal antibodies represent, in the wider settings of immunotherapy, viable options to improve the results obtained in different subsets of patients with acute lymphoblastic leukemia,” wrote Dr. Rizzari.
Echoing the researchers, Dr. Rizzari mentioned the importance of the next step – a phase 3 trial comparing inotuzumab ozogamicin with the current standard of care – but also mentioned that a specific, widely recognized standard of care for this patient subgroup is difficult to pin down.
Dr. Rizzari is with the Pediatric Hematology-Oncology Unit of the University of Milano-Bicocca in Milan. These comments are based on an accompanying editorial published online in Lancet Oncology (2018 Jan 15. doi: 10.1016/S1470-2045[18]30013-5 ). Dr. Rizzari declared no competing interests.
according to the results of a single-arm phase 2 study.
After a median follow-up of 29 months, 2-year progression-free survival was 59% with a median of 25 months for 52 patients with newly diagnosed disease who were aged 60 years or older, Hagop Kantarjian, MD, and his associates reported online in the Lancet Oncology.
Nearly every patient experienced an overall response (98%). The treatment also appeared to be safe, Dr. Kantarjian and associates wrote.
They reported that no patient died within 4 weeks of treatment and that four patients experienced veno-occlusive disease. Common grade 3 or 4 side effects included thrombocytopenia (81%), consolidation chemotherapy (69%), hyperglycemia (54%), infections during induction (52%), hypokalemia (31%), increased aminotransferases (19%), hyperbilirubinemia (17%), and hemorrhage (15%). Six patients died from treatment-related side effects, five of whom died from sepsis and one of whom died as a result of veno-occlusive disease.
Inotuzumab ozogamicin is an anti-CD22 monoclonal antibody that is bound to the toxin calicheamicin. It has shown “substantial improvements” for some patient subgroups when added to hyper-CVAD chemotherapy (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with methotrexate and high-dose cytarabine); however, older patients have yet to experience a similar benefit, Dr. Kantarjian and his associates said.
Both CVAD and inotuzumab ozogamicin have shown to be quite toxic for older patients. So – in order limit increased toxicity – Dr. Kantarjian and his associates lowered the intensity of hyper-CVAD. They accomplished this by reducing some aspects of the regimen by up to 50% and eliminating anthracyclines altogether. The researchers referred to this regimen as “mini–hyper-CVD.” The mini–hyper-CVD did not appear to impact activity.
“In our study, activity did not appear to be compromised by the use of lower-intensity chemotherapy in combination with a novel monoclonal antibody,” they wrote.
Dr. Kantarjian and his associates noted that, while they observed fewer deaths compared with previously published data, the number of deaths they did observe in patients who achieved a complete response was high.
They suggested that modifications to the regimen could further improve safety and that such modifications required further research.
For the time being, however, the researchers noted that this low-intensity regimen, in combination in inotuzumab ozogamicin, is highly effective and that these data now require prospective confirmation in a randomized, phase 3 setting.
The study was funded by the MD Anderson Cancer Center. Researchers reported that Pfizer provided inotuzumab ozogamicin free of charge and that Dr. Kantarjian and two other researchers received grants from Pfizer.
SOURCE: Kantarjian H et al. Lancet Oncol. 2018 Jan 15. doi: 10.1016/S1470-2945(18)30011-1.
according to the results of a single-arm phase 2 study.
After a median follow-up of 29 months, 2-year progression-free survival was 59% with a median of 25 months for 52 patients with newly diagnosed disease who were aged 60 years or older, Hagop Kantarjian, MD, and his associates reported online in the Lancet Oncology.
Nearly every patient experienced an overall response (98%). The treatment also appeared to be safe, Dr. Kantarjian and associates wrote.
They reported that no patient died within 4 weeks of treatment and that four patients experienced veno-occlusive disease. Common grade 3 or 4 side effects included thrombocytopenia (81%), consolidation chemotherapy (69%), hyperglycemia (54%), infections during induction (52%), hypokalemia (31%), increased aminotransferases (19%), hyperbilirubinemia (17%), and hemorrhage (15%). Six patients died from treatment-related side effects, five of whom died from sepsis and one of whom died as a result of veno-occlusive disease.
Inotuzumab ozogamicin is an anti-CD22 monoclonal antibody that is bound to the toxin calicheamicin. It has shown “substantial improvements” for some patient subgroups when added to hyper-CVAD chemotherapy (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with methotrexate and high-dose cytarabine); however, older patients have yet to experience a similar benefit, Dr. Kantarjian and his associates said.
Both CVAD and inotuzumab ozogamicin have shown to be quite toxic for older patients. So – in order limit increased toxicity – Dr. Kantarjian and his associates lowered the intensity of hyper-CVAD. They accomplished this by reducing some aspects of the regimen by up to 50% and eliminating anthracyclines altogether. The researchers referred to this regimen as “mini–hyper-CVD.” The mini–hyper-CVD did not appear to impact activity.
“In our study, activity did not appear to be compromised by the use of lower-intensity chemotherapy in combination with a novel monoclonal antibody,” they wrote.
Dr. Kantarjian and his associates noted that, while they observed fewer deaths compared with previously published data, the number of deaths they did observe in patients who achieved a complete response was high.
They suggested that modifications to the regimen could further improve safety and that such modifications required further research.
For the time being, however, the researchers noted that this low-intensity regimen, in combination in inotuzumab ozogamicin, is highly effective and that these data now require prospective confirmation in a randomized, phase 3 setting.
The study was funded by the MD Anderson Cancer Center. Researchers reported that Pfizer provided inotuzumab ozogamicin free of charge and that Dr. Kantarjian and two other researchers received grants from Pfizer.
SOURCE: Kantarjian H et al. Lancet Oncol. 2018 Jan 15. doi: 10.1016/S1470-2945(18)30011-1.
FROM LANCET ONCOLOGY
Key clinical point: Inotuzumab ozogamicin with less intense chemotherapy is safe and effective for older patients with ALL.
Major finding: After a median follow-up of 29 months, 59% of patients experienced 2-year recurrence-free survival, 56% experienced 3-year overall survival and only four patients died within four weeks of treatment.
Data source: Single-arm phase 2 study of 52 patients aged 60 years or older with newly diagnosed Philadelphia chromosome–negative ALL.
Disclosures: The study was funded by a grant from the MD Anderson Cancer Center. Pfizer provided inotuzumab ozogamicin free of charge. Dr. Kantarjian and two other researchers reported receiving grants from Pfizer.
Source: Kantarjian H et al. Lancet Oncol. 2018 Jan 15. doi: 10.1016/S1470-2945(18)30011-1.