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Jennifer Smith is the editor of Oncology Practice, part of MDedge Hematology/Oncology. She was previously the editor of Hematology Times, an editor at Principal Investigators Association, and a reporter at The Oneida Daily Dispatch. She has a BS in journalism.
Combo produces ‘best response rate’ after first relapse in kids with AML
CHICAGO – Administering CPX-351 prior to a three-drug regimen produced a high response rate in pediatric patients with acute myeloid leukemia (AML) in first relapse.
In a phase 1/2 trial, CPX-351 followed by fludarabine, cytarabine, and filgrastim (FLAG) produced an overall response rate of 81%, and 70% of responders had their best response while receiving CPX-351.
“This is the best response rate published in North America for those [pediatric AML patients] in first relapse,” said Todd Cooper, DO, of Seattle Children’s Hospital in Washington.
Dr. Cooper presented results from the phase 1/2 AAML1421 trial (NCT02642965) at the annual meeting of the American Society of Clinical Oncology.
The primary objective of phase 1 was to determine the recommended phase 2 dose and toxicities of CPX-351, a liposomal preparation of cytarabine and daunorubicin. The primary objective of phase 2 was to assess the best response in patients who received CPX-351 in cycle 1 and FLAG in cycle 2.
The trial enrolled 38 AML patients, 6 in the dose-finding phase and 32 in the efficacy phase. The patients’ median age at study entry was 11.91 years (range, 1.81-21.5). Most patients (88.9%) had CNS 1 disease, and most (73.7%) had not received a transplant.
Half of patients had a first complete response (CR) that lasted 180 to 365 days, 13.2% had a first CR lasting less than 180 days, and 36.8% had a first CR lasting more than 1 year.
Dosing and toxicity
During the dose-finding portion of the study, the first dose level of CPX-351 was 135 units/m2 on days 1, 3, and 5. There was one dose-limiting toxicity — grade 3 decrease in ejection fraction — so 135 units/m2 was deemed the recommended phase 2 dose.
The most common grade 3 or higher adverse events observed with CPX-351 in cycle 1 were infections and infestations (47.4%), febrile neutropenia (44.7%), maculopapular rash (39.5%), and prolonged QT interval (18.4%).
The most common grade 3 or higher adverse events observed with FLAG in cycle 2 were febrile neutropenia (23.1%), prolonged QT interval (23.1%), and infections and infestations (19.2%).
Response and survival
There were 37 patients evaluable for response. The overall response rate was defined as CR plus CR without platelet recovery (CRp) plus CR with incomplete hematologic recovery (CRi).
The overall response rate was 81.1% (n = 30), which included 20 CRs (54.1%), 5 CRps (13.5%), and 5 CRis (13.5%). Five patients had a partial response (13.5%), and two patients had treatment failure (5.4%).
During CPX-351 treatment (n = 37), the CR rate was 37.8% (n = 14), the CRp rate was 5.4% (n = 2), and the CRi rate was 32.4% (n = 12).
During FLAG treatment (n = 27), the CR rate was 48.1% (n = 13), the CRp rate was 25.9% (n = 7), and the CRi rate was 7.4% (n = 2).
Of the 25 patients who achieved a CR or CRp at any time, 21 (84%) were minimal residual disease negative by flow cytometry. Twelve patients were minimal residual disease negative after cycle 1.
Most patients who achieved a CRi or better (83.3%) went on to hematopoietic stem cell transplant.
The 2-year overall survival was 47% for all patients and 60% for responders. None of the non-responders were still alive 2 years after therapy.
“The results certainly warrant a phase 3 study of CPX-351,” Dr. Cooper said. “In fact, it is the lead molecule that’s going to be incorporated into the next COG phase 3 study.”
AAML1421 was sponsored by the Children’s Oncology Group in collaboration with the National Cancer Institute. Dr. Cooper disclosed relationships with Juno Therapeutics and Celgene.
SOURCE: Cooper TM et al. ASCO 2019. Abstract 10003.
CHICAGO – Administering CPX-351 prior to a three-drug regimen produced a high response rate in pediatric patients with acute myeloid leukemia (AML) in first relapse.
In a phase 1/2 trial, CPX-351 followed by fludarabine, cytarabine, and filgrastim (FLAG) produced an overall response rate of 81%, and 70% of responders had their best response while receiving CPX-351.
“This is the best response rate published in North America for those [pediatric AML patients] in first relapse,” said Todd Cooper, DO, of Seattle Children’s Hospital in Washington.
Dr. Cooper presented results from the phase 1/2 AAML1421 trial (NCT02642965) at the annual meeting of the American Society of Clinical Oncology.
The primary objective of phase 1 was to determine the recommended phase 2 dose and toxicities of CPX-351, a liposomal preparation of cytarabine and daunorubicin. The primary objective of phase 2 was to assess the best response in patients who received CPX-351 in cycle 1 and FLAG in cycle 2.
The trial enrolled 38 AML patients, 6 in the dose-finding phase and 32 in the efficacy phase. The patients’ median age at study entry was 11.91 years (range, 1.81-21.5). Most patients (88.9%) had CNS 1 disease, and most (73.7%) had not received a transplant.
Half of patients had a first complete response (CR) that lasted 180 to 365 days, 13.2% had a first CR lasting less than 180 days, and 36.8% had a first CR lasting more than 1 year.
Dosing and toxicity
During the dose-finding portion of the study, the first dose level of CPX-351 was 135 units/m2 on days 1, 3, and 5. There was one dose-limiting toxicity — grade 3 decrease in ejection fraction — so 135 units/m2 was deemed the recommended phase 2 dose.
The most common grade 3 or higher adverse events observed with CPX-351 in cycle 1 were infections and infestations (47.4%), febrile neutropenia (44.7%), maculopapular rash (39.5%), and prolonged QT interval (18.4%).
The most common grade 3 or higher adverse events observed with FLAG in cycle 2 were febrile neutropenia (23.1%), prolonged QT interval (23.1%), and infections and infestations (19.2%).
Response and survival
There were 37 patients evaluable for response. The overall response rate was defined as CR plus CR without platelet recovery (CRp) plus CR with incomplete hematologic recovery (CRi).
The overall response rate was 81.1% (n = 30), which included 20 CRs (54.1%), 5 CRps (13.5%), and 5 CRis (13.5%). Five patients had a partial response (13.5%), and two patients had treatment failure (5.4%).
During CPX-351 treatment (n = 37), the CR rate was 37.8% (n = 14), the CRp rate was 5.4% (n = 2), and the CRi rate was 32.4% (n = 12).
During FLAG treatment (n = 27), the CR rate was 48.1% (n = 13), the CRp rate was 25.9% (n = 7), and the CRi rate was 7.4% (n = 2).
Of the 25 patients who achieved a CR or CRp at any time, 21 (84%) were minimal residual disease negative by flow cytometry. Twelve patients were minimal residual disease negative after cycle 1.
Most patients who achieved a CRi or better (83.3%) went on to hematopoietic stem cell transplant.
The 2-year overall survival was 47% for all patients and 60% for responders. None of the non-responders were still alive 2 years after therapy.
“The results certainly warrant a phase 3 study of CPX-351,” Dr. Cooper said. “In fact, it is the lead molecule that’s going to be incorporated into the next COG phase 3 study.”
AAML1421 was sponsored by the Children’s Oncology Group in collaboration with the National Cancer Institute. Dr. Cooper disclosed relationships with Juno Therapeutics and Celgene.
SOURCE: Cooper TM et al. ASCO 2019. Abstract 10003.
CHICAGO – Administering CPX-351 prior to a three-drug regimen produced a high response rate in pediatric patients with acute myeloid leukemia (AML) in first relapse.
In a phase 1/2 trial, CPX-351 followed by fludarabine, cytarabine, and filgrastim (FLAG) produced an overall response rate of 81%, and 70% of responders had their best response while receiving CPX-351.
“This is the best response rate published in North America for those [pediatric AML patients] in first relapse,” said Todd Cooper, DO, of Seattle Children’s Hospital in Washington.
Dr. Cooper presented results from the phase 1/2 AAML1421 trial (NCT02642965) at the annual meeting of the American Society of Clinical Oncology.
The primary objective of phase 1 was to determine the recommended phase 2 dose and toxicities of CPX-351, a liposomal preparation of cytarabine and daunorubicin. The primary objective of phase 2 was to assess the best response in patients who received CPX-351 in cycle 1 and FLAG in cycle 2.
The trial enrolled 38 AML patients, 6 in the dose-finding phase and 32 in the efficacy phase. The patients’ median age at study entry was 11.91 years (range, 1.81-21.5). Most patients (88.9%) had CNS 1 disease, and most (73.7%) had not received a transplant.
Half of patients had a first complete response (CR) that lasted 180 to 365 days, 13.2% had a first CR lasting less than 180 days, and 36.8% had a first CR lasting more than 1 year.
Dosing and toxicity
During the dose-finding portion of the study, the first dose level of CPX-351 was 135 units/m2 on days 1, 3, and 5. There was one dose-limiting toxicity — grade 3 decrease in ejection fraction — so 135 units/m2 was deemed the recommended phase 2 dose.
The most common grade 3 or higher adverse events observed with CPX-351 in cycle 1 were infections and infestations (47.4%), febrile neutropenia (44.7%), maculopapular rash (39.5%), and prolonged QT interval (18.4%).
The most common grade 3 or higher adverse events observed with FLAG in cycle 2 were febrile neutropenia (23.1%), prolonged QT interval (23.1%), and infections and infestations (19.2%).
Response and survival
There were 37 patients evaluable for response. The overall response rate was defined as CR plus CR without platelet recovery (CRp) plus CR with incomplete hematologic recovery (CRi).
The overall response rate was 81.1% (n = 30), which included 20 CRs (54.1%), 5 CRps (13.5%), and 5 CRis (13.5%). Five patients had a partial response (13.5%), and two patients had treatment failure (5.4%).
During CPX-351 treatment (n = 37), the CR rate was 37.8% (n = 14), the CRp rate was 5.4% (n = 2), and the CRi rate was 32.4% (n = 12).
During FLAG treatment (n = 27), the CR rate was 48.1% (n = 13), the CRp rate was 25.9% (n = 7), and the CRi rate was 7.4% (n = 2).
Of the 25 patients who achieved a CR or CRp at any time, 21 (84%) were minimal residual disease negative by flow cytometry. Twelve patients were minimal residual disease negative after cycle 1.
Most patients who achieved a CRi or better (83.3%) went on to hematopoietic stem cell transplant.
The 2-year overall survival was 47% for all patients and 60% for responders. None of the non-responders were still alive 2 years after therapy.
“The results certainly warrant a phase 3 study of CPX-351,” Dr. Cooper said. “In fact, it is the lead molecule that’s going to be incorporated into the next COG phase 3 study.”
AAML1421 was sponsored by the Children’s Oncology Group in collaboration with the National Cancer Institute. Dr. Cooper disclosed relationships with Juno Therapeutics and Celgene.
SOURCE: Cooper TM et al. ASCO 2019. Abstract 10003.
REPORTING FROM ASCO 2019
Trial matches pediatric cancer patients to targeted therapies
Researchers have found they can screen pediatric cancer patients for genetic alterations and match those patients to appropriate targeted therapies.
Thus far, 24% of the patients screened have been matched and assigned to a treatment, and 10% have been enrolled on treatment protocols.
The patients were screened and matched as part of the National Cancer Institute–Children’s Oncology Group Pediatric MATCH (Molecular Analysis for Therapy Choice) trial.
Results from this trial are scheduled to be presented at the annual meeting of the American Society of Clinical Oncology.
Donald Williams Parsons, MD, PhD, of Baylor College of Medicine in Houston, Tex., presented some results at a press briefing in advance of the meeting. “[T]he last 10 years have been an incredible time in terms of learning more about the genetics and underlying molecular basis of both adult and pediatric cancers,” Dr. Parsons said.
He pointed out, however, that it is not yet known if this information will be useful in guiding the treatment of pediatric cancers. Specifically, how many pediatric patients can be matched to targeted therapies, and how effective will those therapies be?
The Pediatric MATCH trial (NCT03155620) was developed to answer these questions. Researchers plan to enroll at least 1,000 patients in this trial. Patients are eligible if they are 1-21 years of age and have refractory or recurrent solid tumors, non-Hodgkin lymphomas, or histiocytic disorders.
After patients are enrolled in the trial, their tumor samples undergo DNA and RNA sequencing, and the results are used to match each patient to a targeted therapy. At present, the trial can match patients to one of 10 drugs:
- larotrectinib (targeting NTRK fusions).
- erdafitinib (targeting FGFR1/2/3/4).
- tazemetostat (targeting EZH2 or members of the SWI/SNF complex).
- LY3023414 (targeting the PI3K/MTOR pathway).
- selumetinib (targeting the MAPK pathway).
- ensartinib (targeting ALK or ROS1).
- vemurafenib (targeting BRAF V600 mutations).
- olaparib (targeting defects in DNA damage repair).
- palbociclib (targeting alterations in cell cycle genes).
- ulixertinib (targeting MAPK pathway mutations).
Early results
From July 2017 through December 2018, 422 patients were enrolled in the trial. The patients had more than 60 different diagnoses, including brain tumors, sarcomas, neuroblastoma, renal and liver cancers, and other malignancies.
The researchers received tumor samples from 390 patients, attempted sequencing of 370 samples (95%), and completed sequencing of 357 samples (92%).
A treatment target was found in 112 (29%) patients, 95 (24%) of those patients were assigned to a treatment, and 39 (10%) were enrolled in a protocol. The median turnaround time from sample receipt to treatment assignment was 15 days.
“In addition to the sequencing being successful, the patients are being matched to the different treatments,” Dr. Parsons said. He added that the study is ongoing, so more of the matched and assigned patients will be enrolled in protocols in the future.
Dr. Parsons also presented results by tumor type. A targetable alteration was identified in 26% (67/255) of all non–central nervous system solid tumors, 13% (10/75) of osteosarcomas, 50% (18/36) of rhabdomyosarcomas, 21% (7/33) of Ewing sarcomas, 25% (9/36) of other sarcomas, 19% (5/26) of renal cancers, 16% (3/19) of carcinomas, 44% (8/18) of neuroblastomas, 43% (3/7) of liver cancers, and 29% (4/14) of “other” tumors.
Drilling down further, Dr. Parsons presented details on specific alterations in one cancer type: astrocytomas. Targetable alterations were found in 74% (29/39) of astrocytomas. This includes NF1 mutations (18%), BRAF V600E (15%), FGFR1 fusions/mutations (10%), BRAF fusions (10%), PIK3CA mutations (8%), NRAS/KRAS mutations (5%), and other alterations.
“Pretty remarkably, in this one diagnosis, there are patients who have been matched to nine of the ten different treatment arms,” Dr. Parsons said. “This study is allowing us to evaluate targeted therapies – specific types of investigational drugs – in patients with many different cancer types, some common, some very rare. So, hopefully, we can study these agents and identify signals of activity where some of these drugs may work for our patients.”
The Pediatric MATCH trial is sponsored by the National Cancer Institute. Dr. Parsons has patents, royalties, and other intellectual property related to genes discovered through sequencing of several adult cancer types.
SOURCE: Parsons DW et al. ASCO 2019, Abstract 10011.
Researchers have found they can screen pediatric cancer patients for genetic alterations and match those patients to appropriate targeted therapies.
Thus far, 24% of the patients screened have been matched and assigned to a treatment, and 10% have been enrolled on treatment protocols.
The patients were screened and matched as part of the National Cancer Institute–Children’s Oncology Group Pediatric MATCH (Molecular Analysis for Therapy Choice) trial.
Results from this trial are scheduled to be presented at the annual meeting of the American Society of Clinical Oncology.
Donald Williams Parsons, MD, PhD, of Baylor College of Medicine in Houston, Tex., presented some results at a press briefing in advance of the meeting. “[T]he last 10 years have been an incredible time in terms of learning more about the genetics and underlying molecular basis of both adult and pediatric cancers,” Dr. Parsons said.
He pointed out, however, that it is not yet known if this information will be useful in guiding the treatment of pediatric cancers. Specifically, how many pediatric patients can be matched to targeted therapies, and how effective will those therapies be?
The Pediatric MATCH trial (NCT03155620) was developed to answer these questions. Researchers plan to enroll at least 1,000 patients in this trial. Patients are eligible if they are 1-21 years of age and have refractory or recurrent solid tumors, non-Hodgkin lymphomas, or histiocytic disorders.
After patients are enrolled in the trial, their tumor samples undergo DNA and RNA sequencing, and the results are used to match each patient to a targeted therapy. At present, the trial can match patients to one of 10 drugs:
- larotrectinib (targeting NTRK fusions).
- erdafitinib (targeting FGFR1/2/3/4).
- tazemetostat (targeting EZH2 or members of the SWI/SNF complex).
- LY3023414 (targeting the PI3K/MTOR pathway).
- selumetinib (targeting the MAPK pathway).
- ensartinib (targeting ALK or ROS1).
- vemurafenib (targeting BRAF V600 mutations).
- olaparib (targeting defects in DNA damage repair).
- palbociclib (targeting alterations in cell cycle genes).
- ulixertinib (targeting MAPK pathway mutations).
Early results
From July 2017 through December 2018, 422 patients were enrolled in the trial. The patients had more than 60 different diagnoses, including brain tumors, sarcomas, neuroblastoma, renal and liver cancers, and other malignancies.
The researchers received tumor samples from 390 patients, attempted sequencing of 370 samples (95%), and completed sequencing of 357 samples (92%).
A treatment target was found in 112 (29%) patients, 95 (24%) of those patients were assigned to a treatment, and 39 (10%) were enrolled in a protocol. The median turnaround time from sample receipt to treatment assignment was 15 days.
“In addition to the sequencing being successful, the patients are being matched to the different treatments,” Dr. Parsons said. He added that the study is ongoing, so more of the matched and assigned patients will be enrolled in protocols in the future.
Dr. Parsons also presented results by tumor type. A targetable alteration was identified in 26% (67/255) of all non–central nervous system solid tumors, 13% (10/75) of osteosarcomas, 50% (18/36) of rhabdomyosarcomas, 21% (7/33) of Ewing sarcomas, 25% (9/36) of other sarcomas, 19% (5/26) of renal cancers, 16% (3/19) of carcinomas, 44% (8/18) of neuroblastomas, 43% (3/7) of liver cancers, and 29% (4/14) of “other” tumors.
Drilling down further, Dr. Parsons presented details on specific alterations in one cancer type: astrocytomas. Targetable alterations were found in 74% (29/39) of astrocytomas. This includes NF1 mutations (18%), BRAF V600E (15%), FGFR1 fusions/mutations (10%), BRAF fusions (10%), PIK3CA mutations (8%), NRAS/KRAS mutations (5%), and other alterations.
“Pretty remarkably, in this one diagnosis, there are patients who have been matched to nine of the ten different treatment arms,” Dr. Parsons said. “This study is allowing us to evaluate targeted therapies – specific types of investigational drugs – in patients with many different cancer types, some common, some very rare. So, hopefully, we can study these agents and identify signals of activity where some of these drugs may work for our patients.”
The Pediatric MATCH trial is sponsored by the National Cancer Institute. Dr. Parsons has patents, royalties, and other intellectual property related to genes discovered through sequencing of several adult cancer types.
SOURCE: Parsons DW et al. ASCO 2019, Abstract 10011.
Researchers have found they can screen pediatric cancer patients for genetic alterations and match those patients to appropriate targeted therapies.
Thus far, 24% of the patients screened have been matched and assigned to a treatment, and 10% have been enrolled on treatment protocols.
The patients were screened and matched as part of the National Cancer Institute–Children’s Oncology Group Pediatric MATCH (Molecular Analysis for Therapy Choice) trial.
Results from this trial are scheduled to be presented at the annual meeting of the American Society of Clinical Oncology.
Donald Williams Parsons, MD, PhD, of Baylor College of Medicine in Houston, Tex., presented some results at a press briefing in advance of the meeting. “[T]he last 10 years have been an incredible time in terms of learning more about the genetics and underlying molecular basis of both adult and pediatric cancers,” Dr. Parsons said.
He pointed out, however, that it is not yet known if this information will be useful in guiding the treatment of pediatric cancers. Specifically, how many pediatric patients can be matched to targeted therapies, and how effective will those therapies be?
The Pediatric MATCH trial (NCT03155620) was developed to answer these questions. Researchers plan to enroll at least 1,000 patients in this trial. Patients are eligible if they are 1-21 years of age and have refractory or recurrent solid tumors, non-Hodgkin lymphomas, or histiocytic disorders.
After patients are enrolled in the trial, their tumor samples undergo DNA and RNA sequencing, and the results are used to match each patient to a targeted therapy. At present, the trial can match patients to one of 10 drugs:
- larotrectinib (targeting NTRK fusions).
- erdafitinib (targeting FGFR1/2/3/4).
- tazemetostat (targeting EZH2 or members of the SWI/SNF complex).
- LY3023414 (targeting the PI3K/MTOR pathway).
- selumetinib (targeting the MAPK pathway).
- ensartinib (targeting ALK or ROS1).
- vemurafenib (targeting BRAF V600 mutations).
- olaparib (targeting defects in DNA damage repair).
- palbociclib (targeting alterations in cell cycle genes).
- ulixertinib (targeting MAPK pathway mutations).
Early results
From July 2017 through December 2018, 422 patients were enrolled in the trial. The patients had more than 60 different diagnoses, including brain tumors, sarcomas, neuroblastoma, renal and liver cancers, and other malignancies.
The researchers received tumor samples from 390 patients, attempted sequencing of 370 samples (95%), and completed sequencing of 357 samples (92%).
A treatment target was found in 112 (29%) patients, 95 (24%) of those patients were assigned to a treatment, and 39 (10%) were enrolled in a protocol. The median turnaround time from sample receipt to treatment assignment was 15 days.
“In addition to the sequencing being successful, the patients are being matched to the different treatments,” Dr. Parsons said. He added that the study is ongoing, so more of the matched and assigned patients will be enrolled in protocols in the future.
Dr. Parsons also presented results by tumor type. A targetable alteration was identified in 26% (67/255) of all non–central nervous system solid tumors, 13% (10/75) of osteosarcomas, 50% (18/36) of rhabdomyosarcomas, 21% (7/33) of Ewing sarcomas, 25% (9/36) of other sarcomas, 19% (5/26) of renal cancers, 16% (3/19) of carcinomas, 44% (8/18) of neuroblastomas, 43% (3/7) of liver cancers, and 29% (4/14) of “other” tumors.
Drilling down further, Dr. Parsons presented details on specific alterations in one cancer type: astrocytomas. Targetable alterations were found in 74% (29/39) of astrocytomas. This includes NF1 mutations (18%), BRAF V600E (15%), FGFR1 fusions/mutations (10%), BRAF fusions (10%), PIK3CA mutations (8%), NRAS/KRAS mutations (5%), and other alterations.
“Pretty remarkably, in this one diagnosis, there are patients who have been matched to nine of the ten different treatment arms,” Dr. Parsons said. “This study is allowing us to evaluate targeted therapies – specific types of investigational drugs – in patients with many different cancer types, some common, some very rare. So, hopefully, we can study these agents and identify signals of activity where some of these drugs may work for our patients.”
The Pediatric MATCH trial is sponsored by the National Cancer Institute. Dr. Parsons has patents, royalties, and other intellectual property related to genes discovered through sequencing of several adult cancer types.
SOURCE: Parsons DW et al. ASCO 2019, Abstract 10011.
REPORTING FROM ASCO 2019
Entrectinib exhibits activity in children with solid tumors
Entrectinib demonstrated “very promising” antitumor activity in children and adolescents with recurrent or refractory solid tumors, according to an investigator involved in a phase 1/1b trial.
Twelve of 29 patients enrolled in the trial have responded to entrectinib. All responders had fusions in genes targeted by the drug – NTRK1/2/3 (TRKA/B/C), ROS1, or ALK – or an ALK mutation.
Details of this study are scheduled to be presented at the annual meeting of the American Society of Clinical Oncology.
Giles W. Robinson, MD, of St. Jude Children’s Research Hospital in Memphis, Tenn., discussed the study during a press briefing in advance of the meeting.
“Entrectinib is an oral and potent inhibitor of the TRKA/B/C, ROS1, and ALK proteins, but it also penetrates into the brain to reach tumors in the brain and spine, which can be a hard area to get drugs to,” Dr. Robinson explained.
“Promising clinical activity was initially seen in the adult solid tumor patients with target rearrangements, and it was encouraging to see these patients also had responses when the tumors were located in their brains. And what got us really excited as pediatric oncologists was that a variety of pediatric cancers harbor these fusions and mutations within certain tumors.”
With this in mind, Dr. Robinson and colleagues conducted a phase 1/1b study (NCT02650401) of entrectinib in 29 patients with recurrent or refractory solid tumors, including central nervous system (CNS) tumors.
The patients’ median age was 7 years (range, 0-20 years), and roughly half of them were male (n = 15). Patients were diagnosed with neuroblastoma (n = 16), high-grade glioma (n = 5), inflammatory myofibroblastic tumors (n = 3), infantile fibrosarcoma (n = 2), CNS embryonal tumor (n = 1), melanoma (n = 1), and synovial sarcoma (n = 1).
In the dose-finding portion of the trial, patients received entrectinib at 250 mg/m2 (n = 3), 400 mg/m2 (n = 3), 550 mg/m2 (n = 7), or 750 mg/m2 (n = 3).
In the phase 1b portion, patients received entrectinib at 550 mg/m2 (n = 7) – the recommended dose – or 400 mg/m2 (n = 6) if they were unable to swallow intact capsules.
Dr. Robinson said entrectinib was “quite well tolerated” overall, but he did not present any data on adverse events. He did say dose-limiting toxicities included fatigue, elevated creatinine levels, dysgeusia resulting in loss of taste, weight gain, and, in one patient, pulmonary edema.
“Entrectinib produced striking, rapid, and durable responses in all children with refractory CNS and solid tumors that actually harbored these fusions in NTRK1/2/3, ROS1, or ALK,” Dr. Robinson said. “It also produced a significant response in one ALK-mutated neuroblastoma patient. [N]o responses were seen in tumors lacking aberrations in the target kinases.”
In all, 12 patients responded. The three complete responders had an ALK F1174L mutation, an ALK fusion, and an NTRK fusion, respectively. Five partial responders had NTRK fusions, three had ROS1 fusions, and one had an ALK fusion.
Three responders discontinued treatment. Ten patients were still receiving entrectinib at last follow-up, and 11 patients had died.
Progression-free survival was significantly longer among patients who had fusions than among those who did not (P less than .0001).
“To sum up, entrectinib really is very promising,” Dr. Robinson said. “It has very promising antitumor activity and progression-free survival but [only] in patients with target gene fusions.”
Dr. Robinson said this trial is ongoing, but it is now limited to patients with fusions targeted by entrectinib.
The trial is sponsored by Hoffman-La Roche Ltd. and supported by Alex’s Lemonade Stand Center of Excellence. Dr. Robinson has relationships with Lilly, Genentech/Roche, and Novartis.
SOURCE: Robinson GW et al. ASCO 2019. Abstract 10009.
Entrectinib demonstrated “very promising” antitumor activity in children and adolescents with recurrent or refractory solid tumors, according to an investigator involved in a phase 1/1b trial.
Twelve of 29 patients enrolled in the trial have responded to entrectinib. All responders had fusions in genes targeted by the drug – NTRK1/2/3 (TRKA/B/C), ROS1, or ALK – or an ALK mutation.
Details of this study are scheduled to be presented at the annual meeting of the American Society of Clinical Oncology.
Giles W. Robinson, MD, of St. Jude Children’s Research Hospital in Memphis, Tenn., discussed the study during a press briefing in advance of the meeting.
“Entrectinib is an oral and potent inhibitor of the TRKA/B/C, ROS1, and ALK proteins, but it also penetrates into the brain to reach tumors in the brain and spine, which can be a hard area to get drugs to,” Dr. Robinson explained.
“Promising clinical activity was initially seen in the adult solid tumor patients with target rearrangements, and it was encouraging to see these patients also had responses when the tumors were located in their brains. And what got us really excited as pediatric oncologists was that a variety of pediatric cancers harbor these fusions and mutations within certain tumors.”
With this in mind, Dr. Robinson and colleagues conducted a phase 1/1b study (NCT02650401) of entrectinib in 29 patients with recurrent or refractory solid tumors, including central nervous system (CNS) tumors.
The patients’ median age was 7 years (range, 0-20 years), and roughly half of them were male (n = 15). Patients were diagnosed with neuroblastoma (n = 16), high-grade glioma (n = 5), inflammatory myofibroblastic tumors (n = 3), infantile fibrosarcoma (n = 2), CNS embryonal tumor (n = 1), melanoma (n = 1), and synovial sarcoma (n = 1).
In the dose-finding portion of the trial, patients received entrectinib at 250 mg/m2 (n = 3), 400 mg/m2 (n = 3), 550 mg/m2 (n = 7), or 750 mg/m2 (n = 3).
In the phase 1b portion, patients received entrectinib at 550 mg/m2 (n = 7) – the recommended dose – or 400 mg/m2 (n = 6) if they were unable to swallow intact capsules.
Dr. Robinson said entrectinib was “quite well tolerated” overall, but he did not present any data on adverse events. He did say dose-limiting toxicities included fatigue, elevated creatinine levels, dysgeusia resulting in loss of taste, weight gain, and, in one patient, pulmonary edema.
“Entrectinib produced striking, rapid, and durable responses in all children with refractory CNS and solid tumors that actually harbored these fusions in NTRK1/2/3, ROS1, or ALK,” Dr. Robinson said. “It also produced a significant response in one ALK-mutated neuroblastoma patient. [N]o responses were seen in tumors lacking aberrations in the target kinases.”
In all, 12 patients responded. The three complete responders had an ALK F1174L mutation, an ALK fusion, and an NTRK fusion, respectively. Five partial responders had NTRK fusions, three had ROS1 fusions, and one had an ALK fusion.
Three responders discontinued treatment. Ten patients were still receiving entrectinib at last follow-up, and 11 patients had died.
Progression-free survival was significantly longer among patients who had fusions than among those who did not (P less than .0001).
“To sum up, entrectinib really is very promising,” Dr. Robinson said. “It has very promising antitumor activity and progression-free survival but [only] in patients with target gene fusions.”
Dr. Robinson said this trial is ongoing, but it is now limited to patients with fusions targeted by entrectinib.
The trial is sponsored by Hoffman-La Roche Ltd. and supported by Alex’s Lemonade Stand Center of Excellence. Dr. Robinson has relationships with Lilly, Genentech/Roche, and Novartis.
SOURCE: Robinson GW et al. ASCO 2019. Abstract 10009.
Entrectinib demonstrated “very promising” antitumor activity in children and adolescents with recurrent or refractory solid tumors, according to an investigator involved in a phase 1/1b trial.
Twelve of 29 patients enrolled in the trial have responded to entrectinib. All responders had fusions in genes targeted by the drug – NTRK1/2/3 (TRKA/B/C), ROS1, or ALK – or an ALK mutation.
Details of this study are scheduled to be presented at the annual meeting of the American Society of Clinical Oncology.
Giles W. Robinson, MD, of St. Jude Children’s Research Hospital in Memphis, Tenn., discussed the study during a press briefing in advance of the meeting.
“Entrectinib is an oral and potent inhibitor of the TRKA/B/C, ROS1, and ALK proteins, but it also penetrates into the brain to reach tumors in the brain and spine, which can be a hard area to get drugs to,” Dr. Robinson explained.
“Promising clinical activity was initially seen in the adult solid tumor patients with target rearrangements, and it was encouraging to see these patients also had responses when the tumors were located in their brains. And what got us really excited as pediatric oncologists was that a variety of pediatric cancers harbor these fusions and mutations within certain tumors.”
With this in mind, Dr. Robinson and colleagues conducted a phase 1/1b study (NCT02650401) of entrectinib in 29 patients with recurrent or refractory solid tumors, including central nervous system (CNS) tumors.
The patients’ median age was 7 years (range, 0-20 years), and roughly half of them were male (n = 15). Patients were diagnosed with neuroblastoma (n = 16), high-grade glioma (n = 5), inflammatory myofibroblastic tumors (n = 3), infantile fibrosarcoma (n = 2), CNS embryonal tumor (n = 1), melanoma (n = 1), and synovial sarcoma (n = 1).
In the dose-finding portion of the trial, patients received entrectinib at 250 mg/m2 (n = 3), 400 mg/m2 (n = 3), 550 mg/m2 (n = 7), or 750 mg/m2 (n = 3).
In the phase 1b portion, patients received entrectinib at 550 mg/m2 (n = 7) – the recommended dose – or 400 mg/m2 (n = 6) if they were unable to swallow intact capsules.
Dr. Robinson said entrectinib was “quite well tolerated” overall, but he did not present any data on adverse events. He did say dose-limiting toxicities included fatigue, elevated creatinine levels, dysgeusia resulting in loss of taste, weight gain, and, in one patient, pulmonary edema.
“Entrectinib produced striking, rapid, and durable responses in all children with refractory CNS and solid tumors that actually harbored these fusions in NTRK1/2/3, ROS1, or ALK,” Dr. Robinson said. “It also produced a significant response in one ALK-mutated neuroblastoma patient. [N]o responses were seen in tumors lacking aberrations in the target kinases.”
In all, 12 patients responded. The three complete responders had an ALK F1174L mutation, an ALK fusion, and an NTRK fusion, respectively. Five partial responders had NTRK fusions, three had ROS1 fusions, and one had an ALK fusion.
Three responders discontinued treatment. Ten patients were still receiving entrectinib at last follow-up, and 11 patients had died.
Progression-free survival was significantly longer among patients who had fusions than among those who did not (P less than .0001).
“To sum up, entrectinib really is very promising,” Dr. Robinson said. “It has very promising antitumor activity and progression-free survival but [only] in patients with target gene fusions.”
Dr. Robinson said this trial is ongoing, but it is now limited to patients with fusions targeted by entrectinib.
The trial is sponsored by Hoffman-La Roche Ltd. and supported by Alex’s Lemonade Stand Center of Excellence. Dr. Robinson has relationships with Lilly, Genentech/Roche, and Novartis.
SOURCE: Robinson GW et al. ASCO 2019. Abstract 10009.
REPORTING FROM ASCO 2019
NCCN and MD Anderson award funding to researchers
The National Comprehensive Cancer Network (NCCN) and the University of Texas MD Anderson Cancer Center have awarded funding to investigators conducting a range of research projects looking at everything from chimeric antigen receptor T-cell therapy in lung cancer to financial toxicity to fecal microbiota transplantation.
Four researchers won funding through the NCCN Young Investigator Awards, which are supported by the NCCN Foundation, Astra Zeneca, Merck & Co., Genentech, Pfizer, and Incyte.
Prasanna Ananth, MD, of Yale Cancer Center in New Haven, Conn., won funding for her work investigating benchmarks for high quality end-of-life care in children with cancer.
Jaehyuk Choi, MD, PhD, of Northwestern University in Chicago won for his research investigating genomic determinants of response to immunotherapy in Merkel cell carcinoma.
Kedar Kirtane, MD, of Moffitt Cancer Center in Tampa won for his work on a digitized peer-to-peer patient support system for patients with locally advanced head and neck cancer who are receiving chemoradiation.
Yanming Li, PhD, of the University of Michigan in Ann Arbor won for network genome-wide association studies for early detection of cancers.
Meanwhile, the University of Texas MD Anderson Cancer Center named eight researchers to this year’s class of Andrew Sabin Family Fellows. Each researcher will receive $100,000 in funding over 2 years through a $30-million endowment from the Andrew Sabin Family Foundation.
Lauren Averett Byers, MD, is conducting research on the first chimeric antigen receptor T-cell therapy for small cell lung cancer.
Florencia McAllister, MD, is studying the intratumoral bacteria detected in pancreatic cancer patients and the use of fecal microbial transplants to improve treatment outcomes.
Jose Alejandro Rauh-Hain, MD, is attempting to improve gynecologic genetic testing and risk-reduction interventions in underserved populations.
Grace Li Smith, MD, PhD, is researching financial toxicity in patients with early-stage breast cancer who are treated with short-course versus standard adjuvant radiation.
Ishwaria Mohan Subbiah, MD, is investigating a personalized, technology-enhanced symptom-management strategy to provide holistic care for patients on phase 1 trials.
Andrea Viale, MD, is studying the effects of transient inflammation and the role of epithelial memory during progression of pancreatic ductal adenocarcinoma.
Linghua Wang, PhD, is investigating TIM-3 as a potential target for treating peritoneal carcinomatosis in patients with advanced gastric cancer.
Yinghong Wang, MD, PhD, is researching fecal microbiota transplantation as an option for managing immune-mediated colitis following cancer immunotherapy.
Movers in Medicine highlights career moves and personal achievements by hematologists and oncologists. Did you switch jobs, take on a new role, climb a mountain? Tell us all about it at [email protected], and you could be featured in Movers in Medicine.
The National Comprehensive Cancer Network (NCCN) and the University of Texas MD Anderson Cancer Center have awarded funding to investigators conducting a range of research projects looking at everything from chimeric antigen receptor T-cell therapy in lung cancer to financial toxicity to fecal microbiota transplantation.
Four researchers won funding through the NCCN Young Investigator Awards, which are supported by the NCCN Foundation, Astra Zeneca, Merck & Co., Genentech, Pfizer, and Incyte.
Prasanna Ananth, MD, of Yale Cancer Center in New Haven, Conn., won funding for her work investigating benchmarks for high quality end-of-life care in children with cancer.
Jaehyuk Choi, MD, PhD, of Northwestern University in Chicago won for his research investigating genomic determinants of response to immunotherapy in Merkel cell carcinoma.
Kedar Kirtane, MD, of Moffitt Cancer Center in Tampa won for his work on a digitized peer-to-peer patient support system for patients with locally advanced head and neck cancer who are receiving chemoradiation.
Yanming Li, PhD, of the University of Michigan in Ann Arbor won for network genome-wide association studies for early detection of cancers.
Meanwhile, the University of Texas MD Anderson Cancer Center named eight researchers to this year’s class of Andrew Sabin Family Fellows. Each researcher will receive $100,000 in funding over 2 years through a $30-million endowment from the Andrew Sabin Family Foundation.
Lauren Averett Byers, MD, is conducting research on the first chimeric antigen receptor T-cell therapy for small cell lung cancer.
Florencia McAllister, MD, is studying the intratumoral bacteria detected in pancreatic cancer patients and the use of fecal microbial transplants to improve treatment outcomes.
Jose Alejandro Rauh-Hain, MD, is attempting to improve gynecologic genetic testing and risk-reduction interventions in underserved populations.
Grace Li Smith, MD, PhD, is researching financial toxicity in patients with early-stage breast cancer who are treated with short-course versus standard adjuvant radiation.
Ishwaria Mohan Subbiah, MD, is investigating a personalized, technology-enhanced symptom-management strategy to provide holistic care for patients on phase 1 trials.
Andrea Viale, MD, is studying the effects of transient inflammation and the role of epithelial memory during progression of pancreatic ductal adenocarcinoma.
Linghua Wang, PhD, is investigating TIM-3 as a potential target for treating peritoneal carcinomatosis in patients with advanced gastric cancer.
Yinghong Wang, MD, PhD, is researching fecal microbiota transplantation as an option for managing immune-mediated colitis following cancer immunotherapy.
Movers in Medicine highlights career moves and personal achievements by hematologists and oncologists. Did you switch jobs, take on a new role, climb a mountain? Tell us all about it at [email protected], and you could be featured in Movers in Medicine.
The National Comprehensive Cancer Network (NCCN) and the University of Texas MD Anderson Cancer Center have awarded funding to investigators conducting a range of research projects looking at everything from chimeric antigen receptor T-cell therapy in lung cancer to financial toxicity to fecal microbiota transplantation.
Four researchers won funding through the NCCN Young Investigator Awards, which are supported by the NCCN Foundation, Astra Zeneca, Merck & Co., Genentech, Pfizer, and Incyte.
Prasanna Ananth, MD, of Yale Cancer Center in New Haven, Conn., won funding for her work investigating benchmarks for high quality end-of-life care in children with cancer.
Jaehyuk Choi, MD, PhD, of Northwestern University in Chicago won for his research investigating genomic determinants of response to immunotherapy in Merkel cell carcinoma.
Kedar Kirtane, MD, of Moffitt Cancer Center in Tampa won for his work on a digitized peer-to-peer patient support system for patients with locally advanced head and neck cancer who are receiving chemoradiation.
Yanming Li, PhD, of the University of Michigan in Ann Arbor won for network genome-wide association studies for early detection of cancers.
Meanwhile, the University of Texas MD Anderson Cancer Center named eight researchers to this year’s class of Andrew Sabin Family Fellows. Each researcher will receive $100,000 in funding over 2 years through a $30-million endowment from the Andrew Sabin Family Foundation.
Lauren Averett Byers, MD, is conducting research on the first chimeric antigen receptor T-cell therapy for small cell lung cancer.
Florencia McAllister, MD, is studying the intratumoral bacteria detected in pancreatic cancer patients and the use of fecal microbial transplants to improve treatment outcomes.
Jose Alejandro Rauh-Hain, MD, is attempting to improve gynecologic genetic testing and risk-reduction interventions in underserved populations.
Grace Li Smith, MD, PhD, is researching financial toxicity in patients with early-stage breast cancer who are treated with short-course versus standard adjuvant radiation.
Ishwaria Mohan Subbiah, MD, is investigating a personalized, technology-enhanced symptom-management strategy to provide holistic care for patients on phase 1 trials.
Andrea Viale, MD, is studying the effects of transient inflammation and the role of epithelial memory during progression of pancreatic ductal adenocarcinoma.
Linghua Wang, PhD, is investigating TIM-3 as a potential target for treating peritoneal carcinomatosis in patients with advanced gastric cancer.
Yinghong Wang, MD, PhD, is researching fecal microbiota transplantation as an option for managing immune-mediated colitis following cancer immunotherapy.
Movers in Medicine highlights career moves and personal achievements by hematologists and oncologists. Did you switch jobs, take on a new role, climb a mountain? Tell us all about it at [email protected], and you could be featured in Movers in Medicine.
NGS comparable to FC for minimal residual disease assessment
NEW ORLEANS – Next-generation sequencing of peripheral blood is at least as effective as flow cytometry of bone marrow for assessing minimal residual disease, according to a new study.
Researchers compared bone marrow flow cytometry (FC) and peripheral blood next-generation sequencing (NGS) for minimal residual disease (MRD) assessment in pediatric and young adult patients with B-cell acute lymphoblastic leukemia (B-ALL) who received treatment with tisagenlecleucel. There was a high level of concordance between the assays, but the NGS assay detected more MRD-positive samples and NGS results provided a longer lead time to relapse.
Michael A. Pulsipher, MD, of the Children’s Hospital Los Angeles, presented these results at the annual meeting of the American Society of Pediatric Hematology/Oncology.
The researchers analyzed samples from pediatric and young adult patients aged 2-25 years who had relapsed or refractory B-ALL and received treatment with tisagenlecleucel on the ELIANA or ENSIGN trials.
The patients had received at least two prior lines of therapy and were ineligible for allogeneic transplant. They received a single dose of tisagenlecleucel. MRD was assessed before tisagenlecleucel infusion, at various time points after infusion, and at relapse.
Dr. Pulsipher and his colleagues compared MRD results from an NGS assay – Adaptive Biotechnologies’ clonoSEQ – using peripheral blood and results from FC of bone marrow. NGS and FC results were available for 237 samples from 83 patients.
After treatment, NGS detected more MRD-positive samples at each sensitivity level tested (10-4, 10-5, and 10-6). At 10-6, NGS detected 18% more MRD-positive samples than did FC – 50% and 32%, respectively.
Detection of MRD positivity prior to relapse was faster with NGS than with FC. In 17 of 34 patients with morphological relapse, NGS provided a median lead time of 67 days. FC provided a median lead time of 39 days in 11 of the 34 patients.
About 80% of patients who had an MRD status of zero by NGS at day 28 remained relapse-free for up to 3 years.
Among complete responders (n = 50), the duration of response was significantly longer in patients who had an MRD status of zero at day 28 by NGS than in patients who had an MRD status greater than zero (P = .0003). Overall survival was significantly better among patients with an MRD status of zero as well (P = .0004).
Dr. Pulsipher said additional studies are needed to confirm these findings and determine the best way to know if a patient has been cured or needs additional therapy after tisagenlecleucel.
Dr. Pulsipher reported relationships with Adaptive Biotech, Novartis, Incyte, Amgen, Bellicum Pharmaceuticals, Medac Pharma, and Miltenyi Biotec. ELIANA and ENSIGN were funded by Novartis, which markets tisagenlecleucel as Kymriah.
SOURCE: Pulsipher MA et al. ASPHO 2019, Abstract 2001.
NEW ORLEANS – Next-generation sequencing of peripheral blood is at least as effective as flow cytometry of bone marrow for assessing minimal residual disease, according to a new study.
Researchers compared bone marrow flow cytometry (FC) and peripheral blood next-generation sequencing (NGS) for minimal residual disease (MRD) assessment in pediatric and young adult patients with B-cell acute lymphoblastic leukemia (B-ALL) who received treatment with tisagenlecleucel. There was a high level of concordance between the assays, but the NGS assay detected more MRD-positive samples and NGS results provided a longer lead time to relapse.
Michael A. Pulsipher, MD, of the Children’s Hospital Los Angeles, presented these results at the annual meeting of the American Society of Pediatric Hematology/Oncology.
The researchers analyzed samples from pediatric and young adult patients aged 2-25 years who had relapsed or refractory B-ALL and received treatment with tisagenlecleucel on the ELIANA or ENSIGN trials.
The patients had received at least two prior lines of therapy and were ineligible for allogeneic transplant. They received a single dose of tisagenlecleucel. MRD was assessed before tisagenlecleucel infusion, at various time points after infusion, and at relapse.
Dr. Pulsipher and his colleagues compared MRD results from an NGS assay – Adaptive Biotechnologies’ clonoSEQ – using peripheral blood and results from FC of bone marrow. NGS and FC results were available for 237 samples from 83 patients.
After treatment, NGS detected more MRD-positive samples at each sensitivity level tested (10-4, 10-5, and 10-6). At 10-6, NGS detected 18% more MRD-positive samples than did FC – 50% and 32%, respectively.
Detection of MRD positivity prior to relapse was faster with NGS than with FC. In 17 of 34 patients with morphological relapse, NGS provided a median lead time of 67 days. FC provided a median lead time of 39 days in 11 of the 34 patients.
About 80% of patients who had an MRD status of zero by NGS at day 28 remained relapse-free for up to 3 years.
Among complete responders (n = 50), the duration of response was significantly longer in patients who had an MRD status of zero at day 28 by NGS than in patients who had an MRD status greater than zero (P = .0003). Overall survival was significantly better among patients with an MRD status of zero as well (P = .0004).
Dr. Pulsipher said additional studies are needed to confirm these findings and determine the best way to know if a patient has been cured or needs additional therapy after tisagenlecleucel.
Dr. Pulsipher reported relationships with Adaptive Biotech, Novartis, Incyte, Amgen, Bellicum Pharmaceuticals, Medac Pharma, and Miltenyi Biotec. ELIANA and ENSIGN were funded by Novartis, which markets tisagenlecleucel as Kymriah.
SOURCE: Pulsipher MA et al. ASPHO 2019, Abstract 2001.
NEW ORLEANS – Next-generation sequencing of peripheral blood is at least as effective as flow cytometry of bone marrow for assessing minimal residual disease, according to a new study.
Researchers compared bone marrow flow cytometry (FC) and peripheral blood next-generation sequencing (NGS) for minimal residual disease (MRD) assessment in pediatric and young adult patients with B-cell acute lymphoblastic leukemia (B-ALL) who received treatment with tisagenlecleucel. There was a high level of concordance between the assays, but the NGS assay detected more MRD-positive samples and NGS results provided a longer lead time to relapse.
Michael A. Pulsipher, MD, of the Children’s Hospital Los Angeles, presented these results at the annual meeting of the American Society of Pediatric Hematology/Oncology.
The researchers analyzed samples from pediatric and young adult patients aged 2-25 years who had relapsed or refractory B-ALL and received treatment with tisagenlecleucel on the ELIANA or ENSIGN trials.
The patients had received at least two prior lines of therapy and were ineligible for allogeneic transplant. They received a single dose of tisagenlecleucel. MRD was assessed before tisagenlecleucel infusion, at various time points after infusion, and at relapse.
Dr. Pulsipher and his colleagues compared MRD results from an NGS assay – Adaptive Biotechnologies’ clonoSEQ – using peripheral blood and results from FC of bone marrow. NGS and FC results were available for 237 samples from 83 patients.
After treatment, NGS detected more MRD-positive samples at each sensitivity level tested (10-4, 10-5, and 10-6). At 10-6, NGS detected 18% more MRD-positive samples than did FC – 50% and 32%, respectively.
Detection of MRD positivity prior to relapse was faster with NGS than with FC. In 17 of 34 patients with morphological relapse, NGS provided a median lead time of 67 days. FC provided a median lead time of 39 days in 11 of the 34 patients.
About 80% of patients who had an MRD status of zero by NGS at day 28 remained relapse-free for up to 3 years.
Among complete responders (n = 50), the duration of response was significantly longer in patients who had an MRD status of zero at day 28 by NGS than in patients who had an MRD status greater than zero (P = .0003). Overall survival was significantly better among patients with an MRD status of zero as well (P = .0004).
Dr. Pulsipher said additional studies are needed to confirm these findings and determine the best way to know if a patient has been cured or needs additional therapy after tisagenlecleucel.
Dr. Pulsipher reported relationships with Adaptive Biotech, Novartis, Incyte, Amgen, Bellicum Pharmaceuticals, Medac Pharma, and Miltenyi Biotec. ELIANA and ENSIGN were funded by Novartis, which markets tisagenlecleucel as Kymriah.
SOURCE: Pulsipher MA et al. ASPHO 2019, Abstract 2001.
REPORTING FROM 2019 ASPHO CONFERENCE
Key clinical point: Major finding: At the highest sensitivity level tested, next-generation sequencing detected 18% more minimal residual disease–positive samples than did flow cytometry – 50% and 32%, respectively.
Study details: An analysis of samples from pediatric and young adult patients with B-cell acute lymphoblastic leukemia who received treatment with tisagenlecleucel on the ELIANA and ENSIGN trials.
Disclosures: The speaker reported relationships with Adaptive Biotech, Novartis, Incyte, Amgen, Bellicum Pharmaceuticals, Medac Pharma, and Miltenyi Biotec. The ELIANA and ENSIGN trials were funded by Novartis, which markets tisagenlecleucel as Kymriah.
Source: Pulsipher MA et al. ASPHO 2019, Abstract 2001.
Low-dose chemo feasible for older, frail patients with advanced gastroesophageal cancer
A low-dose chemotherapy regimen appears safe and effective for older and frail patients with advanced gastroesophageal cancer.
In a phase 3 trial, progression-free survival in patients who received the lowest dose of oxaliplatin and capecitabine was noninferior to progression-free survival in patients who received two higher doses of the combination.
The lowest dose also was associated with better overall treatment utility, which is a composite of clinical benefit, tolerability, quality of life, and patient value.
“[T]his is the largest randomized, controlled trial to date specifically investigating frail or elderly patients with advanced gastroesophageal cancer,” said study investigator Peter S. Hall, PhD, of the University of Edinburgh. “We found that the lowest dose tested was noninferior in terms of progression-free survival, it produced less toxicity, and it had better overall treatment utility.”
These findings are scheduled to be presented at the annual meeting of the American Society of Clinical Oncology. Dr. Hall discussed the findings during a press briefing in advance of the meeting.
The phase 3 trial (ISRCTN44687907) enrolled older and frail patients, aged 51-96 years, with advanced gastroesophageal cancer. Dr. Hall presented data on 514 patients randomized to receive oxaliplatin and capecitabine at one of three dose levels. Dose level A consisted of oxaliplatin given at 130 mg/m2 once every 21 days and capecitabine given at 625 mg/m2 twice a day every day. Dose level B was 80% of the level A dosage, and dose level C was 60% of the level A dosage. Patients with decreased kidney function received 75% of the allocated capecitabine dose.
The trial’s primary endpoint was noninferiority of progression-free survival at 12 months. Noninferiority was confirmed for level B, compared with level A, with a hazard ratio of 1.09, and for level C, compared with level A, with a hazard ratio of 1.10.
“The lowest dose, the level C dose, had the best overall treatment utility … compared to patients either on level A or level B, and this was due to lower side effects and better quality of life,” Dr. Hall said.
Overall treatment utility outcomes were “good” in 35% of the dose A group, 36% of the dose B group, and 43% of the dose C group. Outcomes were “poor” in 31%, 38%, and 29%, respectively, and outcomes were “intermediate” in 34%, 26%, and 27%, respectively.
To achieve “good” overall treatment utility, patients had to achieve the following six domains: cancer doesn’t progress on scans, oncologist assesses a benefit of treatment, lack of severe toxicity, patient’s global quality of life scores aren’t deteriorating, patient scores the treatment as worthwhile, and the patient says the treatment doesn’t interfere with daily activities.
These results suggest low-dose chemotherapy is feasible for older and frail patients with advanced gastroesophageal cancer, according to Dr. Hall.
“[L]ow-dose treatment may be offered to patients who are suitable for chemotherapy but considered too frail or elderly for a full-dose standard regime, in the confidence that it can produce superior outcomes without compromising cancer control or survival,” Dr. Hall said.
Dr. Hall reported relationships with Eisai, Pfizer, Roche, AstraZeneca, Daiichi Sankyo, and Novartis. The trial was funded by Cancer Research UK and sponsored by the University of Leeds (England).
SOURCE: Hall PS et al. ASCO 2019, Abstract 4006.
A low-dose chemotherapy regimen appears safe and effective for older and frail patients with advanced gastroesophageal cancer.
In a phase 3 trial, progression-free survival in patients who received the lowest dose of oxaliplatin and capecitabine was noninferior to progression-free survival in patients who received two higher doses of the combination.
The lowest dose also was associated with better overall treatment utility, which is a composite of clinical benefit, tolerability, quality of life, and patient value.
“[T]his is the largest randomized, controlled trial to date specifically investigating frail or elderly patients with advanced gastroesophageal cancer,” said study investigator Peter S. Hall, PhD, of the University of Edinburgh. “We found that the lowest dose tested was noninferior in terms of progression-free survival, it produced less toxicity, and it had better overall treatment utility.”
These findings are scheduled to be presented at the annual meeting of the American Society of Clinical Oncology. Dr. Hall discussed the findings during a press briefing in advance of the meeting.
The phase 3 trial (ISRCTN44687907) enrolled older and frail patients, aged 51-96 years, with advanced gastroesophageal cancer. Dr. Hall presented data on 514 patients randomized to receive oxaliplatin and capecitabine at one of three dose levels. Dose level A consisted of oxaliplatin given at 130 mg/m2 once every 21 days and capecitabine given at 625 mg/m2 twice a day every day. Dose level B was 80% of the level A dosage, and dose level C was 60% of the level A dosage. Patients with decreased kidney function received 75% of the allocated capecitabine dose.
The trial’s primary endpoint was noninferiority of progression-free survival at 12 months. Noninferiority was confirmed for level B, compared with level A, with a hazard ratio of 1.09, and for level C, compared with level A, with a hazard ratio of 1.10.
“The lowest dose, the level C dose, had the best overall treatment utility … compared to patients either on level A or level B, and this was due to lower side effects and better quality of life,” Dr. Hall said.
Overall treatment utility outcomes were “good” in 35% of the dose A group, 36% of the dose B group, and 43% of the dose C group. Outcomes were “poor” in 31%, 38%, and 29%, respectively, and outcomes were “intermediate” in 34%, 26%, and 27%, respectively.
To achieve “good” overall treatment utility, patients had to achieve the following six domains: cancer doesn’t progress on scans, oncologist assesses a benefit of treatment, lack of severe toxicity, patient’s global quality of life scores aren’t deteriorating, patient scores the treatment as worthwhile, and the patient says the treatment doesn’t interfere with daily activities.
These results suggest low-dose chemotherapy is feasible for older and frail patients with advanced gastroesophageal cancer, according to Dr. Hall.
“[L]ow-dose treatment may be offered to patients who are suitable for chemotherapy but considered too frail or elderly for a full-dose standard regime, in the confidence that it can produce superior outcomes without compromising cancer control or survival,” Dr. Hall said.
Dr. Hall reported relationships with Eisai, Pfizer, Roche, AstraZeneca, Daiichi Sankyo, and Novartis. The trial was funded by Cancer Research UK and sponsored by the University of Leeds (England).
SOURCE: Hall PS et al. ASCO 2019, Abstract 4006.
A low-dose chemotherapy regimen appears safe and effective for older and frail patients with advanced gastroesophageal cancer.
In a phase 3 trial, progression-free survival in patients who received the lowest dose of oxaliplatin and capecitabine was noninferior to progression-free survival in patients who received two higher doses of the combination.
The lowest dose also was associated with better overall treatment utility, which is a composite of clinical benefit, tolerability, quality of life, and patient value.
“[T]his is the largest randomized, controlled trial to date specifically investigating frail or elderly patients with advanced gastroesophageal cancer,” said study investigator Peter S. Hall, PhD, of the University of Edinburgh. “We found that the lowest dose tested was noninferior in terms of progression-free survival, it produced less toxicity, and it had better overall treatment utility.”
These findings are scheduled to be presented at the annual meeting of the American Society of Clinical Oncology. Dr. Hall discussed the findings during a press briefing in advance of the meeting.
The phase 3 trial (ISRCTN44687907) enrolled older and frail patients, aged 51-96 years, with advanced gastroesophageal cancer. Dr. Hall presented data on 514 patients randomized to receive oxaliplatin and capecitabine at one of three dose levels. Dose level A consisted of oxaliplatin given at 130 mg/m2 once every 21 days and capecitabine given at 625 mg/m2 twice a day every day. Dose level B was 80% of the level A dosage, and dose level C was 60% of the level A dosage. Patients with decreased kidney function received 75% of the allocated capecitabine dose.
The trial’s primary endpoint was noninferiority of progression-free survival at 12 months. Noninferiority was confirmed for level B, compared with level A, with a hazard ratio of 1.09, and for level C, compared with level A, with a hazard ratio of 1.10.
“The lowest dose, the level C dose, had the best overall treatment utility … compared to patients either on level A or level B, and this was due to lower side effects and better quality of life,” Dr. Hall said.
Overall treatment utility outcomes were “good” in 35% of the dose A group, 36% of the dose B group, and 43% of the dose C group. Outcomes were “poor” in 31%, 38%, and 29%, respectively, and outcomes were “intermediate” in 34%, 26%, and 27%, respectively.
To achieve “good” overall treatment utility, patients had to achieve the following six domains: cancer doesn’t progress on scans, oncologist assesses a benefit of treatment, lack of severe toxicity, patient’s global quality of life scores aren’t deteriorating, patient scores the treatment as worthwhile, and the patient says the treatment doesn’t interfere with daily activities.
These results suggest low-dose chemotherapy is feasible for older and frail patients with advanced gastroesophageal cancer, according to Dr. Hall.
“[L]ow-dose treatment may be offered to patients who are suitable for chemotherapy but considered too frail or elderly for a full-dose standard regime, in the confidence that it can produce superior outcomes without compromising cancer control or survival,” Dr. Hall said.
Dr. Hall reported relationships with Eisai, Pfizer, Roche, AstraZeneca, Daiichi Sankyo, and Novartis. The trial was funded by Cancer Research UK and sponsored by the University of Leeds (England).
SOURCE: Hall PS et al. ASCO 2019, Abstract 4006.
FROM ASCO 2019
Lenalidomide may reduce risk of progression from SMM to MM
Lenalidomide can reduce the risk of progression from smoldering multiple myeloma (SMM) to multiple myeloma (MM), according to a phase 2/3 trial.
At 3 years, the rate of progression-free survival (PFS) was 91% in SMM patients randomized to lenalidomide and 66% in those randomized to observation.
However, more than half of patients randomized to lenalidomide discontinued treatment because of toxicity.
These results are scheduled to be presented at the annual meeting of the American Society of Clinical Oncology.
Sagar Lonial, MD, of Winship Cancer Institute, Emory University, Atlanta, discussed the results in a press briefing in advance of the meeting.
A prior trial suggested that lenalidomide plus dexamethasone can improve time to MM development and overall survival in patients with high-risk SMM (Mateos MV et al. NEJM 2013). However, inferior imaging was used in this trial, and the addition of dexamethasone hindered researchers’ ability to isolate the effects of lenalidomide, Dr. Lonial said.
With their trial (NCT01169337), Dr. Lonial and colleagues tested lenalidomide alone and screened patients using magnetic resonance imaging.
The trial enrolled patients with intermediate or high-risk SMM in two phases. In phase 2, all 44 patients received lenalidomide at 25 mg daily on days 1-21 of a 28-day cycle. They also received aspirin at 325 mg on days 1-28.
In the phase 3 portion of the trial, 182 patients were randomized to observation or lenalidomide and aspirin at the aforementioned dose and schedule. Patients were stratified according to time since SMM diagnosis – 1 year or less vs. more than 1 year.
Safety
Dr. Lonial said, in general, lenalidomide was “very well tolerated.” However, 80% of patients in phase 2 and 51% in phase 3 discontinued lenalidomide due to toxicity.
The rates of treatment-related adverse events (AEs) in the phase 2 portion were 34.1% for grade 3 AEs, 11.4% for grade 4, and 4.5% for grade 5. In the phase 3 portion, 35.2% of patients had grade 3 treatment-related AEs, and 5.7% had grade 4 treatment-related AEs.
Common AEs in phase 3 were grade 4 neutrophil count decrease (4.5%) and grade 3 infections (20.5%), hypertension (9.1%), fatigue (6.8%), skin AEs (5.7%), dyspnea (5.7%), and hypokalemia (3.4%).
Efficacy
“It is worth noting that about 50% of patients had an objective response to lenalidomide in both the phase 2 and the phase 3 trial,” Dr. Lonial said. “I think it’s also important to realize that, in the phase 2 portion of this study, of the 44 patients enrolled, 78% of them did not progress to myeloma with a median follow-up of over 5 years.”
In phase 2, PFS was 98% at 1 year, 87% at 3 years, and 78% at 5 years.
In phase 3, PFS was 98% in the lenalidomide arm and 89% in the observation arm at 1 year. At 2 years, PFS was 93% in the lenalidomide arm and 76% in the observation arm. At 3 years, PFS was 91% in the lenalidomide arm and 66% in the observation arm.
“What’s really quite interesting is that each [risk] group appeared to benefit almost equally from the early intervention of lenalidomide as a single agent,” Dr. Lonial said. “[W]hile the high-risk group may be the target now, this may be a fertile area for investigation in the intermediate-risk group as well.”
Dr. Lonial has relationships with AbbVie, Amgen, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen Oncology, Juno Therapeutics, Merck, Novartis, and Takeda. The trial was funded by the National Institutes of Health.
SOURCE: Lonial S et al. ASCO 2019. Abstract 8001.
Lenalidomide can reduce the risk of progression from smoldering multiple myeloma (SMM) to multiple myeloma (MM), according to a phase 2/3 trial.
At 3 years, the rate of progression-free survival (PFS) was 91% in SMM patients randomized to lenalidomide and 66% in those randomized to observation.
However, more than half of patients randomized to lenalidomide discontinued treatment because of toxicity.
These results are scheduled to be presented at the annual meeting of the American Society of Clinical Oncology.
Sagar Lonial, MD, of Winship Cancer Institute, Emory University, Atlanta, discussed the results in a press briefing in advance of the meeting.
A prior trial suggested that lenalidomide plus dexamethasone can improve time to MM development and overall survival in patients with high-risk SMM (Mateos MV et al. NEJM 2013). However, inferior imaging was used in this trial, and the addition of dexamethasone hindered researchers’ ability to isolate the effects of lenalidomide, Dr. Lonial said.
With their trial (NCT01169337), Dr. Lonial and colleagues tested lenalidomide alone and screened patients using magnetic resonance imaging.
The trial enrolled patients with intermediate or high-risk SMM in two phases. In phase 2, all 44 patients received lenalidomide at 25 mg daily on days 1-21 of a 28-day cycle. They also received aspirin at 325 mg on days 1-28.
In the phase 3 portion of the trial, 182 patients were randomized to observation or lenalidomide and aspirin at the aforementioned dose and schedule. Patients were stratified according to time since SMM diagnosis – 1 year or less vs. more than 1 year.
Safety
Dr. Lonial said, in general, lenalidomide was “very well tolerated.” However, 80% of patients in phase 2 and 51% in phase 3 discontinued lenalidomide due to toxicity.
The rates of treatment-related adverse events (AEs) in the phase 2 portion were 34.1% for grade 3 AEs, 11.4% for grade 4, and 4.5% for grade 5. In the phase 3 portion, 35.2% of patients had grade 3 treatment-related AEs, and 5.7% had grade 4 treatment-related AEs.
Common AEs in phase 3 were grade 4 neutrophil count decrease (4.5%) and grade 3 infections (20.5%), hypertension (9.1%), fatigue (6.8%), skin AEs (5.7%), dyspnea (5.7%), and hypokalemia (3.4%).
Efficacy
“It is worth noting that about 50% of patients had an objective response to lenalidomide in both the phase 2 and the phase 3 trial,” Dr. Lonial said. “I think it’s also important to realize that, in the phase 2 portion of this study, of the 44 patients enrolled, 78% of them did not progress to myeloma with a median follow-up of over 5 years.”
In phase 2, PFS was 98% at 1 year, 87% at 3 years, and 78% at 5 years.
In phase 3, PFS was 98% in the lenalidomide arm and 89% in the observation arm at 1 year. At 2 years, PFS was 93% in the lenalidomide arm and 76% in the observation arm. At 3 years, PFS was 91% in the lenalidomide arm and 66% in the observation arm.
“What’s really quite interesting is that each [risk] group appeared to benefit almost equally from the early intervention of lenalidomide as a single agent,” Dr. Lonial said. “[W]hile the high-risk group may be the target now, this may be a fertile area for investigation in the intermediate-risk group as well.”
Dr. Lonial has relationships with AbbVie, Amgen, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen Oncology, Juno Therapeutics, Merck, Novartis, and Takeda. The trial was funded by the National Institutes of Health.
SOURCE: Lonial S et al. ASCO 2019. Abstract 8001.
Lenalidomide can reduce the risk of progression from smoldering multiple myeloma (SMM) to multiple myeloma (MM), according to a phase 2/3 trial.
At 3 years, the rate of progression-free survival (PFS) was 91% in SMM patients randomized to lenalidomide and 66% in those randomized to observation.
However, more than half of patients randomized to lenalidomide discontinued treatment because of toxicity.
These results are scheduled to be presented at the annual meeting of the American Society of Clinical Oncology.
Sagar Lonial, MD, of Winship Cancer Institute, Emory University, Atlanta, discussed the results in a press briefing in advance of the meeting.
A prior trial suggested that lenalidomide plus dexamethasone can improve time to MM development and overall survival in patients with high-risk SMM (Mateos MV et al. NEJM 2013). However, inferior imaging was used in this trial, and the addition of dexamethasone hindered researchers’ ability to isolate the effects of lenalidomide, Dr. Lonial said.
With their trial (NCT01169337), Dr. Lonial and colleagues tested lenalidomide alone and screened patients using magnetic resonance imaging.
The trial enrolled patients with intermediate or high-risk SMM in two phases. In phase 2, all 44 patients received lenalidomide at 25 mg daily on days 1-21 of a 28-day cycle. They also received aspirin at 325 mg on days 1-28.
In the phase 3 portion of the trial, 182 patients were randomized to observation or lenalidomide and aspirin at the aforementioned dose and schedule. Patients were stratified according to time since SMM diagnosis – 1 year or less vs. more than 1 year.
Safety
Dr. Lonial said, in general, lenalidomide was “very well tolerated.” However, 80% of patients in phase 2 and 51% in phase 3 discontinued lenalidomide due to toxicity.
The rates of treatment-related adverse events (AEs) in the phase 2 portion were 34.1% for grade 3 AEs, 11.4% for grade 4, and 4.5% for grade 5. In the phase 3 portion, 35.2% of patients had grade 3 treatment-related AEs, and 5.7% had grade 4 treatment-related AEs.
Common AEs in phase 3 were grade 4 neutrophil count decrease (4.5%) and grade 3 infections (20.5%), hypertension (9.1%), fatigue (6.8%), skin AEs (5.7%), dyspnea (5.7%), and hypokalemia (3.4%).
Efficacy
“It is worth noting that about 50% of patients had an objective response to lenalidomide in both the phase 2 and the phase 3 trial,” Dr. Lonial said. “I think it’s also important to realize that, in the phase 2 portion of this study, of the 44 patients enrolled, 78% of them did not progress to myeloma with a median follow-up of over 5 years.”
In phase 2, PFS was 98% at 1 year, 87% at 3 years, and 78% at 5 years.
In phase 3, PFS was 98% in the lenalidomide arm and 89% in the observation arm at 1 year. At 2 years, PFS was 93% in the lenalidomide arm and 76% in the observation arm. At 3 years, PFS was 91% in the lenalidomide arm and 66% in the observation arm.
“What’s really quite interesting is that each [risk] group appeared to benefit almost equally from the early intervention of lenalidomide as a single agent,” Dr. Lonial said. “[W]hile the high-risk group may be the target now, this may be a fertile area for investigation in the intermediate-risk group as well.”
Dr. Lonial has relationships with AbbVie, Amgen, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen Oncology, Juno Therapeutics, Merck, Novartis, and Takeda. The trial was funded by the National Institutes of Health.
SOURCE: Lonial S et al. ASCO 2019. Abstract 8001.
REPORTING FROM ASCO 2019
Diet linked to lower risk of death from breast cancer
A balanced, low-fat diet was associated with a lower risk of death from breast cancer in a large cohort of postmenopausal women who had no previous history of breast cancer.
Researchers studied nearly 49,000 postmenopausal women and found a 21% lower risk of death from breast cancer among women who followed the balanced, low-fat diet, compared with women who followed their normal diet.
This research is scheduled to be presented at the annual meeting of the American Society of Clinical Oncology.
Rowan Chlebowski, MD, PhD, of the Los Angeles Biomedical Research Institute at Harbor–UCLA Medical Center in Torrance, Calif., discussed the research during a press briefing in advance of the meeting.
About the study
The research is part of the Woman’s Health Initiative (NCT00000611), which is focused on investigating methods for preventing heart disease, breast and colorectal cancer, and osteoporotic fractures in postmenopausal women.
This trial enrolled 48,835 postmenopausal women, ages 50-79 years, with no history of breast cancer and normal mammograms at enrollment. From 1993 to 1998, the women were randomized to the study diet (n = 19,541) or their normal diet (n = 29,294).
With the normal diet, fat accounted for 32% or more of subjects’ daily calories. With the study diet, the goal was to reduce fat consumption to 20% or less of caloric intake. The study diet also required at least one daily serving of vegetables, fruits, and grains.
Dr. Chlebowski said the study diet is similar to DASH (Dietary Approaches to Stop Hypertension), but is slightly more focused on lowering fat intake.
Diet adherence
Subjects followed the study diet for a median of 8.5 years, and the median cumulative follow-up was 19.6 years.
Dr. Chlebowski noted that most women on the study diet were not able to reduce their daily fat consumption to the 20% goal. They did reduce fat consumption to 24.5% overall, which increased to 29% at the end of the intervention.
In the study-diet group, there was an average weight loss of 3%, significantly different from that of the normal-diet group (P less than .001).
Dr. Chlebowski said the weight loss indicates that subjects did adhere to the study diet, at least in part, as there was no change in physical activity among study participants. Furthermore, the researchers have evidence after 1 year that suggests subjects were incorporating more fruits and vegetables into their diets.
Breast cancer and death
At a median follow-up of 19.6 years, there were 3,374 cases of breast cancer, 1,011 deaths, and 383 deaths attributed to breast cancer.
The risk of death from breast cancer was significantly lower in the study-diet group than in the normal-diet group. The hazard ratio was 0.79 (95% confidence interval, 0.64-0.97; P = .025).
The risk of death (from any cause) after breast cancer was significantly lower in the study diet group as well, with a hazard ratio of 0.85 (95% confidence interval, 0.74-0.96; P = .01).
“Adoption of a low-fat dietary pattern reduces the risk of death from breast cancer in postmenopausal women,” Dr. Chlebowski said. “To our review, this is the only study providing randomized clinical trial evidence that an intervention can reduce a woman’s risk of dying from breast cancer.”
Dr. Chlebowski noted that the researchers have blood samples from all subjects enrolled in this study. The researchers plan to analyze those samples to further explore how the study diet affected the women and determine which components of the diet account for which effects.
The National Institutes of Health funded the study. The researchers disclosed relationships with Novartis, Pfizer, Amgen, AstraZeneca, Immunomedics, Metastat, Bayer, and Genentech/Roche.
SOURCE: Chlebowski R. et al. ASCO 2019. Abstract 520.
A balanced, low-fat diet was associated with a lower risk of death from breast cancer in a large cohort of postmenopausal women who had no previous history of breast cancer.
Researchers studied nearly 49,000 postmenopausal women and found a 21% lower risk of death from breast cancer among women who followed the balanced, low-fat diet, compared with women who followed their normal diet.
This research is scheduled to be presented at the annual meeting of the American Society of Clinical Oncology.
Rowan Chlebowski, MD, PhD, of the Los Angeles Biomedical Research Institute at Harbor–UCLA Medical Center in Torrance, Calif., discussed the research during a press briefing in advance of the meeting.
About the study
The research is part of the Woman’s Health Initiative (NCT00000611), which is focused on investigating methods for preventing heart disease, breast and colorectal cancer, and osteoporotic fractures in postmenopausal women.
This trial enrolled 48,835 postmenopausal women, ages 50-79 years, with no history of breast cancer and normal mammograms at enrollment. From 1993 to 1998, the women were randomized to the study diet (n = 19,541) or their normal diet (n = 29,294).
With the normal diet, fat accounted for 32% or more of subjects’ daily calories. With the study diet, the goal was to reduce fat consumption to 20% or less of caloric intake. The study diet also required at least one daily serving of vegetables, fruits, and grains.
Dr. Chlebowski said the study diet is similar to DASH (Dietary Approaches to Stop Hypertension), but is slightly more focused on lowering fat intake.
Diet adherence
Subjects followed the study diet for a median of 8.5 years, and the median cumulative follow-up was 19.6 years.
Dr. Chlebowski noted that most women on the study diet were not able to reduce their daily fat consumption to the 20% goal. They did reduce fat consumption to 24.5% overall, which increased to 29% at the end of the intervention.
In the study-diet group, there was an average weight loss of 3%, significantly different from that of the normal-diet group (P less than .001).
Dr. Chlebowski said the weight loss indicates that subjects did adhere to the study diet, at least in part, as there was no change in physical activity among study participants. Furthermore, the researchers have evidence after 1 year that suggests subjects were incorporating more fruits and vegetables into their diets.
Breast cancer and death
At a median follow-up of 19.6 years, there were 3,374 cases of breast cancer, 1,011 deaths, and 383 deaths attributed to breast cancer.
The risk of death from breast cancer was significantly lower in the study-diet group than in the normal-diet group. The hazard ratio was 0.79 (95% confidence interval, 0.64-0.97; P = .025).
The risk of death (from any cause) after breast cancer was significantly lower in the study diet group as well, with a hazard ratio of 0.85 (95% confidence interval, 0.74-0.96; P = .01).
“Adoption of a low-fat dietary pattern reduces the risk of death from breast cancer in postmenopausal women,” Dr. Chlebowski said. “To our review, this is the only study providing randomized clinical trial evidence that an intervention can reduce a woman’s risk of dying from breast cancer.”
Dr. Chlebowski noted that the researchers have blood samples from all subjects enrolled in this study. The researchers plan to analyze those samples to further explore how the study diet affected the women and determine which components of the diet account for which effects.
The National Institutes of Health funded the study. The researchers disclosed relationships with Novartis, Pfizer, Amgen, AstraZeneca, Immunomedics, Metastat, Bayer, and Genentech/Roche.
SOURCE: Chlebowski R. et al. ASCO 2019. Abstract 520.
A balanced, low-fat diet was associated with a lower risk of death from breast cancer in a large cohort of postmenopausal women who had no previous history of breast cancer.
Researchers studied nearly 49,000 postmenopausal women and found a 21% lower risk of death from breast cancer among women who followed the balanced, low-fat diet, compared with women who followed their normal diet.
This research is scheduled to be presented at the annual meeting of the American Society of Clinical Oncology.
Rowan Chlebowski, MD, PhD, of the Los Angeles Biomedical Research Institute at Harbor–UCLA Medical Center in Torrance, Calif., discussed the research during a press briefing in advance of the meeting.
About the study
The research is part of the Woman’s Health Initiative (NCT00000611), which is focused on investigating methods for preventing heart disease, breast and colorectal cancer, and osteoporotic fractures in postmenopausal women.
This trial enrolled 48,835 postmenopausal women, ages 50-79 years, with no history of breast cancer and normal mammograms at enrollment. From 1993 to 1998, the women were randomized to the study diet (n = 19,541) or their normal diet (n = 29,294).
With the normal diet, fat accounted for 32% or more of subjects’ daily calories. With the study diet, the goal was to reduce fat consumption to 20% or less of caloric intake. The study diet also required at least one daily serving of vegetables, fruits, and grains.
Dr. Chlebowski said the study diet is similar to DASH (Dietary Approaches to Stop Hypertension), but is slightly more focused on lowering fat intake.
Diet adherence
Subjects followed the study diet for a median of 8.5 years, and the median cumulative follow-up was 19.6 years.
Dr. Chlebowski noted that most women on the study diet were not able to reduce their daily fat consumption to the 20% goal. They did reduce fat consumption to 24.5% overall, which increased to 29% at the end of the intervention.
In the study-diet group, there was an average weight loss of 3%, significantly different from that of the normal-diet group (P less than .001).
Dr. Chlebowski said the weight loss indicates that subjects did adhere to the study diet, at least in part, as there was no change in physical activity among study participants. Furthermore, the researchers have evidence after 1 year that suggests subjects were incorporating more fruits and vegetables into their diets.
Breast cancer and death
At a median follow-up of 19.6 years, there were 3,374 cases of breast cancer, 1,011 deaths, and 383 deaths attributed to breast cancer.
The risk of death from breast cancer was significantly lower in the study-diet group than in the normal-diet group. The hazard ratio was 0.79 (95% confidence interval, 0.64-0.97; P = .025).
The risk of death (from any cause) after breast cancer was significantly lower in the study diet group as well, with a hazard ratio of 0.85 (95% confidence interval, 0.74-0.96; P = .01).
“Adoption of a low-fat dietary pattern reduces the risk of death from breast cancer in postmenopausal women,” Dr. Chlebowski said. “To our review, this is the only study providing randomized clinical trial evidence that an intervention can reduce a woman’s risk of dying from breast cancer.”
Dr. Chlebowski noted that the researchers have blood samples from all subjects enrolled in this study. The researchers plan to analyze those samples to further explore how the study diet affected the women and determine which components of the diet account for which effects.
The National Institutes of Health funded the study. The researchers disclosed relationships with Novartis, Pfizer, Amgen, AstraZeneca, Immunomedics, Metastat, Bayer, and Genentech/Roche.
SOURCE: Chlebowski R. et al. ASCO 2019. Abstract 520.
REPORTING FROM ASCO 2019
Key clinical point: Women who followed a balanced, low-fat diet had a lower risk of death from breast cancer compared with women who followed their normal diet.
Major finding: The risk of death from breast cancer was significantly lower in the study-diet group than in the normal-diet group (hazard ratio, 0.79, 95% confidence interval, 0.64-0.97; P = .025).
Study details: A cohort from the Women’s Health Initiative, which randomized 48,835 postmenopausal women to a low-fat diet or to their normal diet.
Disclosures: The National Institutes of Health funded the study. The researchers disclosed relationships with Novartis, Pfizer, Amgen, AstraZeneca, Immunomedics, Metastat, Bayer, and Genentech/Roche.
Source: Chlebowski R. et al. ASCO 2019. Abstract 520.
QOL concerns prompt second-line therapy in children with ITP
NEW ORLEANS – In a survey of pediatric hematologists, quality of life was the most frequently cited reason for starting second-line therapy in children with immune thrombocytopenia.
Quality of life (QOL) was an indication for second-line treatment in nearly three-quarters of patients studied, and it ranked among the top three indications – along with bleeding frequency and bleeding severity – for treatment in more than half of patients.
Kristin A. Shimano, MD, of the department of pediatrics at the University of California, San Francisco, presented these results at the annual meeting of the American Society of Pediatric Hematology/Oncology.
Dr. Shimano and colleagues surveyed hematologists treating children in the ICON1 study (Am J Hematol. 2019 Apr 3. doi: 10.1002/ajh.25479).
The study enrolled 120 children receiving second-line immune thrombocytopenia (ITP) treatment at 21 centers. The median age at enrollment was 11.7 years (range, 1.2-17.8 years). About half of patients (53%) had chronic ITP, 31% had persistent ITP, and 16% had newly diagnosed ITP. The median number of prior treatments was three (range, zero to eight).
At study entry, the hematologists were asked to provide reasons that patients required second-line treatment. The list of 12 possible reasons included patient or parent QOL; bleeding severity; bleeding frequency; severity of thrombocytopenia; chronicity of ITP; high baseline activity level; involvement in sports; patient age; distance from medical center; and parent, patient, or physician anxiety. The hematologists were asked to choose all reasons that applied and to rank the top three reasons.
QOL was chosen as a reason to treat in 73% of patients (n = 88). QOL was among the top three reasons in 57% of patients (n = 68) and was the most important reason in 27% of patients (n = 32).
The severity and frequency of bleeding were ranked among the top three indications as well. Bleeding severity was a top indication in 29% of cases (n = 35), and bleeding frequency was a top indication in 40% of cases (n = 48).
Reasons for starting second-line treatment varied depending on patients’ phase of disease.
Bleeding severity was significantly more likely to be an indication for treatment among patients who had newly diagnosed or persistent ITP (69%), rather than chronic ITP (31%; P = .0025). Bleeding frequency was also significantly more likely to be an indication among patients with newly diagnosed or persistent ITP (63% vs. 37%; P = .0054).
Conversely, QOL was significantly more likely to be an indication for patients with chronic ITP (65%) rather than newly diagnosed or persistent ITP (35%, P = .0056). Sports participation was a more likely indication among patients with chronic ITP as well (75% vs. 26%, P = .017).
Indications for treatment also varied according to baseline platelet counts. For example, QOL was an indication for treatment in 42% of patients with baseline platelet counts less than 10 x 109/L and 78% of patients with platelet counts of 20 x 109/L or greater. So the higher the baseline platelet count, the more likely QOL was an indication for treatment (P = .006).
On the other hand, the importance hematologists placed on QOL did not appear to correlate with actual health-related QOL as assessed by the Kids ITP Tool. There was no difference reported in baseline health-related QOL, according to the tool, in children for whom QOL was ranked versus unranked by hematologists.
This finding suggests physicians may not be adequately assessing the impact of ITP on QOL, Dr. Shimano said.
“Better clinical measures of the impact of ITP on patient quality of life are needed to assess both need for treatment and treatment response,” she said. “Understanding the effects of individual second-line treatments on quality of life is critical for this patient population in order to best tailor therapy for each patient.”
Dr. Shimano reported involvement in an investigator-initiated trial for eltrombopag in children with ITP. The study, which has not yet opened, is funded by Novartis.
SOURCE: Shimano KA et al. ASPHO 2019, Abstract 2012.
NEW ORLEANS – In a survey of pediatric hematologists, quality of life was the most frequently cited reason for starting second-line therapy in children with immune thrombocytopenia.
Quality of life (QOL) was an indication for second-line treatment in nearly three-quarters of patients studied, and it ranked among the top three indications – along with bleeding frequency and bleeding severity – for treatment in more than half of patients.
Kristin A. Shimano, MD, of the department of pediatrics at the University of California, San Francisco, presented these results at the annual meeting of the American Society of Pediatric Hematology/Oncology.
Dr. Shimano and colleagues surveyed hematologists treating children in the ICON1 study (Am J Hematol. 2019 Apr 3. doi: 10.1002/ajh.25479).
The study enrolled 120 children receiving second-line immune thrombocytopenia (ITP) treatment at 21 centers. The median age at enrollment was 11.7 years (range, 1.2-17.8 years). About half of patients (53%) had chronic ITP, 31% had persistent ITP, and 16% had newly diagnosed ITP. The median number of prior treatments was three (range, zero to eight).
At study entry, the hematologists were asked to provide reasons that patients required second-line treatment. The list of 12 possible reasons included patient or parent QOL; bleeding severity; bleeding frequency; severity of thrombocytopenia; chronicity of ITP; high baseline activity level; involvement in sports; patient age; distance from medical center; and parent, patient, or physician anxiety. The hematologists were asked to choose all reasons that applied and to rank the top three reasons.
QOL was chosen as a reason to treat in 73% of patients (n = 88). QOL was among the top three reasons in 57% of patients (n = 68) and was the most important reason in 27% of patients (n = 32).
The severity and frequency of bleeding were ranked among the top three indications as well. Bleeding severity was a top indication in 29% of cases (n = 35), and bleeding frequency was a top indication in 40% of cases (n = 48).
Reasons for starting second-line treatment varied depending on patients’ phase of disease.
Bleeding severity was significantly more likely to be an indication for treatment among patients who had newly diagnosed or persistent ITP (69%), rather than chronic ITP (31%; P = .0025). Bleeding frequency was also significantly more likely to be an indication among patients with newly diagnosed or persistent ITP (63% vs. 37%; P = .0054).
Conversely, QOL was significantly more likely to be an indication for patients with chronic ITP (65%) rather than newly diagnosed or persistent ITP (35%, P = .0056). Sports participation was a more likely indication among patients with chronic ITP as well (75% vs. 26%, P = .017).
Indications for treatment also varied according to baseline platelet counts. For example, QOL was an indication for treatment in 42% of patients with baseline platelet counts less than 10 x 109/L and 78% of patients with platelet counts of 20 x 109/L or greater. So the higher the baseline platelet count, the more likely QOL was an indication for treatment (P = .006).
On the other hand, the importance hematologists placed on QOL did not appear to correlate with actual health-related QOL as assessed by the Kids ITP Tool. There was no difference reported in baseline health-related QOL, according to the tool, in children for whom QOL was ranked versus unranked by hematologists.
This finding suggests physicians may not be adequately assessing the impact of ITP on QOL, Dr. Shimano said.
“Better clinical measures of the impact of ITP on patient quality of life are needed to assess both need for treatment and treatment response,” she said. “Understanding the effects of individual second-line treatments on quality of life is critical for this patient population in order to best tailor therapy for each patient.”
Dr. Shimano reported involvement in an investigator-initiated trial for eltrombopag in children with ITP. The study, which has not yet opened, is funded by Novartis.
SOURCE: Shimano KA et al. ASPHO 2019, Abstract 2012.
NEW ORLEANS – In a survey of pediatric hematologists, quality of life was the most frequently cited reason for starting second-line therapy in children with immune thrombocytopenia.
Quality of life (QOL) was an indication for second-line treatment in nearly three-quarters of patients studied, and it ranked among the top three indications – along with bleeding frequency and bleeding severity – for treatment in more than half of patients.
Kristin A. Shimano, MD, of the department of pediatrics at the University of California, San Francisco, presented these results at the annual meeting of the American Society of Pediatric Hematology/Oncology.
Dr. Shimano and colleagues surveyed hematologists treating children in the ICON1 study (Am J Hematol. 2019 Apr 3. doi: 10.1002/ajh.25479).
The study enrolled 120 children receiving second-line immune thrombocytopenia (ITP) treatment at 21 centers. The median age at enrollment was 11.7 years (range, 1.2-17.8 years). About half of patients (53%) had chronic ITP, 31% had persistent ITP, and 16% had newly diagnosed ITP. The median number of prior treatments was three (range, zero to eight).
At study entry, the hematologists were asked to provide reasons that patients required second-line treatment. The list of 12 possible reasons included patient or parent QOL; bleeding severity; bleeding frequency; severity of thrombocytopenia; chronicity of ITP; high baseline activity level; involvement in sports; patient age; distance from medical center; and parent, patient, or physician anxiety. The hematologists were asked to choose all reasons that applied and to rank the top three reasons.
QOL was chosen as a reason to treat in 73% of patients (n = 88). QOL was among the top three reasons in 57% of patients (n = 68) and was the most important reason in 27% of patients (n = 32).
The severity and frequency of bleeding were ranked among the top three indications as well. Bleeding severity was a top indication in 29% of cases (n = 35), and bleeding frequency was a top indication in 40% of cases (n = 48).
Reasons for starting second-line treatment varied depending on patients’ phase of disease.
Bleeding severity was significantly more likely to be an indication for treatment among patients who had newly diagnosed or persistent ITP (69%), rather than chronic ITP (31%; P = .0025). Bleeding frequency was also significantly more likely to be an indication among patients with newly diagnosed or persistent ITP (63% vs. 37%; P = .0054).
Conversely, QOL was significantly more likely to be an indication for patients with chronic ITP (65%) rather than newly diagnosed or persistent ITP (35%, P = .0056). Sports participation was a more likely indication among patients with chronic ITP as well (75% vs. 26%, P = .017).
Indications for treatment also varied according to baseline platelet counts. For example, QOL was an indication for treatment in 42% of patients with baseline platelet counts less than 10 x 109/L and 78% of patients with platelet counts of 20 x 109/L or greater. So the higher the baseline platelet count, the more likely QOL was an indication for treatment (P = .006).
On the other hand, the importance hematologists placed on QOL did not appear to correlate with actual health-related QOL as assessed by the Kids ITP Tool. There was no difference reported in baseline health-related QOL, according to the tool, in children for whom QOL was ranked versus unranked by hematologists.
This finding suggests physicians may not be adequately assessing the impact of ITP on QOL, Dr. Shimano said.
“Better clinical measures of the impact of ITP on patient quality of life are needed to assess both need for treatment and treatment response,” she said. “Understanding the effects of individual second-line treatments on quality of life is critical for this patient population in order to best tailor therapy for each patient.”
Dr. Shimano reported involvement in an investigator-initiated trial for eltrombopag in children with ITP. The study, which has not yet opened, is funded by Novartis.
SOURCE: Shimano KA et al. ASPHO 2019, Abstract 2012.
REPORTING FROM THE 2019 ASPHO CONFERENCE
Key clinical point: Quality of life was the most frequently cited reason for starting second-line therapy in children with immune thrombocytopenia.
Major finding: Quality of life was chosen as a reason to treat in 73% of patients, it was among the top three reasons in 57% of patients, and it was the most important reason in 27%.
Study details: A survey of hematologists treating 120 children in an observational study.
Disclosures: The speaker reported involvement in an investigator-initiated trial for eltrombopag in children with ITP. The study, which has not yet opened, is funded by Novartis.
Source: Shimano KA et al. ASPHO 2019, Abstract 2012.
Master trial seeks to aid drug development for pediatric AML
NEW ORLEANS – Researchers are organizing a master trial in an attempt to improve the treatment of pediatric acute myeloid leukemia (AML).
The Pediatric Acute Leukemia (PedAL) trial is an effort to collect data on all pediatric AML patients. The plan is to use these data to match patients to clinical trials, better understand pediatric AML, and bring new treatments to this population.
E. Anders Kolb, MD, of Nemours Center for Cancer and Blood Disorders in Wilmington, Del., described the initiative at the annual meeting of the American Society of Pediatric Hematology/Oncology.
Dr. Kolb noted that several drugs have been approved to treat adult AML in the last 2 years, but most of them are not approved for use in children.
“What we see in childhood AML is a lot different than what we see in adult AML, and this challenges the paradigm that we have traditionally followed where we use the adult as the 'preclinical model' for pediatric AML,” he said. “I think we are learning more and more that children have a unique disease, unique targets, and need unique therapies.”
The PedAL initiative is an attempt to address these unique needs. PedAL is part of the Leukemia & Lymphoma Society’s Children’s Initiative, and it involves researchers from academic centers and the Children’s Oncology Group.
The PedAL initiative includes preclinical, biomarker, and informatics research, as well as the master clinical trial. The main goal of the master trial is to collect genomic, proteomic, metabolomic, flow cytometry, and clinical data from all children with AML and use these data to match patients to clinical trials.
The PedAL trial will leverage Project:EveryChild, an effort by the Children’s Oncology Group to study every child with cancer. Each child enrolled in this program has an identification number that follows the child through all clinical interventions.
The goal is that Project:EveryChild will capture all pediatric AML patients at the time of diagnosis, although patients can join the project at any time. Then, sequencing, clinical, and other data will be collected from these patients and stored in a data commons.
If patients relapse after standard or other therapies, the GEARBOX algorithm (genomic eligibility algorithm at relapse for better outcomes) can be used to match the patient’s information to clinical trial eligibility criteria and provide a list of appropriate trials.
Dr. Kolb said this process should reduce logistical barriers and get relapsed patients to trials more quickly. Additionally, the data collected through PedAL should help researchers design better trials for pediatric patients with relapsed AML.
“Ultimately, we’ll create the largest data set that will give us a better understanding of all the risks and benefits associated with postrelapse AML,” Dr. Kolb said. “No matter what happens to the patient, no matter where that patient enrolls, we’re going to have the capacity to collect data and present that data to the community for analysis for improved understanding of outcomes.”
Dr. Kolb and his colleagues are already working with researchers in Europe and Japan to make this a global effort and create an international data commons. In addition, the researchers are planning to collaborate with the pharmaceutical industry to unite efforts in pediatric AML drug development.
“We can’t just test drugs in kids because they worked in adults,” Dr. Kolb said. “We really need to maintain the integrity of the science and ask relevant questions in children but do so with the intent to make sure these drugs are licensed for use in kids.”
Dr. Kolb reported having no conflicts of interest. The PedAL trial is sponsored by the Leukemia & Lymphoma Society.
NEW ORLEANS – Researchers are organizing a master trial in an attempt to improve the treatment of pediatric acute myeloid leukemia (AML).
The Pediatric Acute Leukemia (PedAL) trial is an effort to collect data on all pediatric AML patients. The plan is to use these data to match patients to clinical trials, better understand pediatric AML, and bring new treatments to this population.
E. Anders Kolb, MD, of Nemours Center for Cancer and Blood Disorders in Wilmington, Del., described the initiative at the annual meeting of the American Society of Pediatric Hematology/Oncology.
Dr. Kolb noted that several drugs have been approved to treat adult AML in the last 2 years, but most of them are not approved for use in children.
“What we see in childhood AML is a lot different than what we see in adult AML, and this challenges the paradigm that we have traditionally followed where we use the adult as the 'preclinical model' for pediatric AML,” he said. “I think we are learning more and more that children have a unique disease, unique targets, and need unique therapies.”
The PedAL initiative is an attempt to address these unique needs. PedAL is part of the Leukemia & Lymphoma Society’s Children’s Initiative, and it involves researchers from academic centers and the Children’s Oncology Group.
The PedAL initiative includes preclinical, biomarker, and informatics research, as well as the master clinical trial. The main goal of the master trial is to collect genomic, proteomic, metabolomic, flow cytometry, and clinical data from all children with AML and use these data to match patients to clinical trials.
The PedAL trial will leverage Project:EveryChild, an effort by the Children’s Oncology Group to study every child with cancer. Each child enrolled in this program has an identification number that follows the child through all clinical interventions.
The goal is that Project:EveryChild will capture all pediatric AML patients at the time of diagnosis, although patients can join the project at any time. Then, sequencing, clinical, and other data will be collected from these patients and stored in a data commons.
If patients relapse after standard or other therapies, the GEARBOX algorithm (genomic eligibility algorithm at relapse for better outcomes) can be used to match the patient’s information to clinical trial eligibility criteria and provide a list of appropriate trials.
Dr. Kolb said this process should reduce logistical barriers and get relapsed patients to trials more quickly. Additionally, the data collected through PedAL should help researchers design better trials for pediatric patients with relapsed AML.
“Ultimately, we’ll create the largest data set that will give us a better understanding of all the risks and benefits associated with postrelapse AML,” Dr. Kolb said. “No matter what happens to the patient, no matter where that patient enrolls, we’re going to have the capacity to collect data and present that data to the community for analysis for improved understanding of outcomes.”
Dr. Kolb and his colleagues are already working with researchers in Europe and Japan to make this a global effort and create an international data commons. In addition, the researchers are planning to collaborate with the pharmaceutical industry to unite efforts in pediatric AML drug development.
“We can’t just test drugs in kids because they worked in adults,” Dr. Kolb said. “We really need to maintain the integrity of the science and ask relevant questions in children but do so with the intent to make sure these drugs are licensed for use in kids.”
Dr. Kolb reported having no conflicts of interest. The PedAL trial is sponsored by the Leukemia & Lymphoma Society.
NEW ORLEANS – Researchers are organizing a master trial in an attempt to improve the treatment of pediatric acute myeloid leukemia (AML).
The Pediatric Acute Leukemia (PedAL) trial is an effort to collect data on all pediatric AML patients. The plan is to use these data to match patients to clinical trials, better understand pediatric AML, and bring new treatments to this population.
E. Anders Kolb, MD, of Nemours Center for Cancer and Blood Disorders in Wilmington, Del., described the initiative at the annual meeting of the American Society of Pediatric Hematology/Oncology.
Dr. Kolb noted that several drugs have been approved to treat adult AML in the last 2 years, but most of them are not approved for use in children.
“What we see in childhood AML is a lot different than what we see in adult AML, and this challenges the paradigm that we have traditionally followed where we use the adult as the 'preclinical model' for pediatric AML,” he said. “I think we are learning more and more that children have a unique disease, unique targets, and need unique therapies.”
The PedAL initiative is an attempt to address these unique needs. PedAL is part of the Leukemia & Lymphoma Society’s Children’s Initiative, and it involves researchers from academic centers and the Children’s Oncology Group.
The PedAL initiative includes preclinical, biomarker, and informatics research, as well as the master clinical trial. The main goal of the master trial is to collect genomic, proteomic, metabolomic, flow cytometry, and clinical data from all children with AML and use these data to match patients to clinical trials.
The PedAL trial will leverage Project:EveryChild, an effort by the Children’s Oncology Group to study every child with cancer. Each child enrolled in this program has an identification number that follows the child through all clinical interventions.
The goal is that Project:EveryChild will capture all pediatric AML patients at the time of diagnosis, although patients can join the project at any time. Then, sequencing, clinical, and other data will be collected from these patients and stored in a data commons.
If patients relapse after standard or other therapies, the GEARBOX algorithm (genomic eligibility algorithm at relapse for better outcomes) can be used to match the patient’s information to clinical trial eligibility criteria and provide a list of appropriate trials.
Dr. Kolb said this process should reduce logistical barriers and get relapsed patients to trials more quickly. Additionally, the data collected through PedAL should help researchers design better trials for pediatric patients with relapsed AML.
“Ultimately, we’ll create the largest data set that will give us a better understanding of all the risks and benefits associated with postrelapse AML,” Dr. Kolb said. “No matter what happens to the patient, no matter where that patient enrolls, we’re going to have the capacity to collect data and present that data to the community for analysis for improved understanding of outcomes.”
Dr. Kolb and his colleagues are already working with researchers in Europe and Japan to make this a global effort and create an international data commons. In addition, the researchers are planning to collaborate with the pharmaceutical industry to unite efforts in pediatric AML drug development.
“We can’t just test drugs in kids because they worked in adults,” Dr. Kolb said. “We really need to maintain the integrity of the science and ask relevant questions in children but do so with the intent to make sure these drugs are licensed for use in kids.”
Dr. Kolb reported having no conflicts of interest. The PedAL trial is sponsored by the Leukemia & Lymphoma Society.
REPORTING FROM 2019 ASPHO CONFERENCE
