Leukemia, Myelodysplasia, Transplantation

©ASCO/Rodney White 2018

CHICAGO—Two agents targeting novel pathways in myeloid malignancies—mivebresib and bencentinib—are showing promise in early studies, according to a speaker at the 2018 ASCO Annual Meeting.

“Both BET and AXL inhibition appear to be new and exciting targets in myeloid malignancies,” said Alice S. Mims, MD, and both have produced responses as single agents.

Dr Mims, of Ohio State University Wexner Medical Center in Columbus, made these observations in a poster discussion presentation that included commentary on the two agents.

Mivebresib (ABBV-075), an inhibitor of bromodomain and extra terminal (BET) proteins, yielded some responses in relapsed/refractory acute myeloid leukemia (AML) patients in a first-in-human study presented at the meeting (abstract 7019*).

Bemcentinib (BGB324), a first-in class selective inhibitor of the AXL tyrosine kinase, also showed activity in preliminary results of a study including patients with relapsed/refractory disease (abstract 7020*).

“It will be important to know individual patient characteristics to determine the potential response predictors,” Dr Mims said.

Mivebresib (NCT02391480)

Mivebresib is the subject of an ongoing phase 1 dose-escalation study in which 23 patients have been treated. That includes 12 who received the BET inhibitor as monotherapy, and 11 who got it in combination with the BCL-2 inhibitor venetoclax, which is indicated in CLL and has breakthrough therapy designation for AML.

Investigators observed responses in 3 of 17 evaluable patients (17.6%), including 1 complete remission with incomplete blood count recovery in a patient on mivebresib monotherapy, plus 1 partial response and 1 patient achieving a morphologic leukemia-free state with the combination.

The most common grade 3/4 treatment-emergent adverse events included anemia in 52%, thrombocytopenia in 44%, and febrile neutropenia in 26% of patients, with no dose-limiting toxicities noted as of this report.

Bemcentinib (NCT02488408)

Bemcentinib is being evaluated in a phase 1/2 trial including patients with relapsed/refractory AML and myelodysplastic syndromes (MDS).

For 32 patients treated so far, 3 patients achieved a complete remission, including 1 AML and 2 MDS patients.

In addition, 3 patients achieved partial response, including 1 MDS and 2 AML patients.

Treatment with bemcentinib was generally well-tolerated, and most adverse events were mild or moderate, investigators reported in their poster.

Pre-treatment levels of soluble AXL were lower in responders compared with non-responders, investigators also noted.

“Soluble AXL levels may be a predictive biomarker for AXL inhibition, but further assessment is necessary,” Dr Mims said. 

*Data presented at the meeting differ from the abstracts.

©ASCO/Rodney White 2018

CHICAGO—Two agents targeting novel pathways in myeloid malignancies—mivebresib and bencentinib—are showing promise in early studies, according to a speaker at the 2018 ASCO Annual Meeting.

“Both BET and AXL inhibition appear to be new and exciting targets in myeloid malignancies,” said Alice S. Mims, MD, and both have produced responses as single agents.

Dr Mims, of Ohio State University Wexner Medical Center in Columbus, made these observations in a poster discussion presentation that included commentary on the two agents.

Mivebresib (ABBV-075), an inhibitor of bromodomain and extra terminal (BET) proteins, yielded some responses in relapsed/refractory acute myeloid leukemia (AML) patients in a first-in-human study presented at the meeting (abstract 7019*).

Bemcentinib (BGB324), a first-in class selective inhibitor of the AXL tyrosine kinase, also showed activity in preliminary results of a study including patients with relapsed/refractory disease (abstract 7020*).

“It will be important to know individual patient characteristics to determine the potential response predictors,” Dr Mims said.

Mivebresib (NCT02391480)

Mivebresib is the subject of an ongoing phase 1 dose-escalation study in which 23 patients have been treated. That includes 12 who received the BET inhibitor as monotherapy, and 11 who got it in combination with the BCL-2 inhibitor venetoclax, which is indicated in CLL and has breakthrough therapy designation for AML.

Investigators observed responses in 3 of 17 evaluable patients (17.6%), including 1 complete remission with incomplete blood count recovery in a patient on mivebresib monotherapy, plus 1 partial response and 1 patient achieving a morphologic leukemia-free state with the combination.

The most common grade 3/4 treatment-emergent adverse events included anemia in 52%, thrombocytopenia in 44%, and febrile neutropenia in 26% of patients, with no dose-limiting toxicities noted as of this report.

Bemcentinib (NCT02488408)

Bemcentinib is being evaluated in a phase 1/2 trial including patients with relapsed/refractory AML and myelodysplastic syndromes (MDS).

For 32 patients treated so far, 3 patients achieved a complete remission, including 1 AML and 2 MDS patients.

In addition, 3 patients achieved partial response, including 1 MDS and 2 AML patients.

Treatment with bemcentinib was generally well-tolerated, and most adverse events were mild or moderate, investigators reported in their poster.

Pre-treatment levels of soluble AXL were lower in responders compared with non-responders, investigators also noted.

“Soluble AXL levels may be a predictive biomarker for AXL inhibition, but further assessment is necessary,” Dr Mims said. 

*Data presented at the meeting differ from the abstracts.

©ASCO/Rodney White 2018

CHICAGO—Two agents targeting novel pathways in myeloid malignancies—mivebresib and bencentinib—are showing promise in early studies, according to a speaker at the 2018 ASCO Annual Meeting.

“Both BET and AXL inhibition appear to be new and exciting targets in myeloid malignancies,” said Alice S. Mims, MD, and both have produced responses as single agents.

Dr Mims, of Ohio State University Wexner Medical Center in Columbus, made these observations in a poster discussion presentation that included commentary on the two agents.

Mivebresib (ABBV-075), an inhibitor of bromodomain and extra terminal (BET) proteins, yielded some responses in relapsed/refractory acute myeloid leukemia (AML) patients in a first-in-human study presented at the meeting (abstract 7019*).

Bemcentinib (BGB324), a first-in class selective inhibitor of the AXL tyrosine kinase, also showed activity in preliminary results of a study including patients with relapsed/refractory disease (abstract 7020*).

“It will be important to know individual patient characteristics to determine the potential response predictors,” Dr Mims said.

Mivebresib (NCT02391480)

Mivebresib is the subject of an ongoing phase 1 dose-escalation study in which 23 patients have been treated. That includes 12 who received the BET inhibitor as monotherapy, and 11 who got it in combination with the BCL-2 inhibitor venetoclax, which is indicated in CLL and has breakthrough therapy designation for AML.

Investigators observed responses in 3 of 17 evaluable patients (17.6%), including 1 complete remission with incomplete blood count recovery in a patient on mivebresib monotherapy, plus 1 partial response and 1 patient achieving a morphologic leukemia-free state with the combination.

The most common grade 3/4 treatment-emergent adverse events included anemia in 52%, thrombocytopenia in 44%, and febrile neutropenia in 26% of patients, with no dose-limiting toxicities noted as of this report.

Bemcentinib (NCT02488408)

Bemcentinib is being evaluated in a phase 1/2 trial including patients with relapsed/refractory AML and myelodysplastic syndromes (MDS).

For 32 patients treated so far, 3 patients achieved a complete remission, including 1 AML and 2 MDS patients.

In addition, 3 patients achieved partial response, including 1 MDS and 2 AML patients.

Treatment with bemcentinib was generally well-tolerated, and most adverse events were mild or moderate, investigators reported in their poster.

Pre-treatment levels of soluble AXL were lower in responders compared with non-responders, investigators also noted.

“Soluble AXL levels may be a predictive biomarker for AXL inhibition, but further assessment is necessary,” Dr Mims said. 

*Data presented at the meeting differ from the abstracts.

CHICAGO – Minimal residual disease (MRD)–negative complete remission was strongly associated with improved survival outcomes in patients with B-cell acute lymphocytic leukemia (ALL) who received CD19 chimeric antigen receptor (CAR) T cells, results of a retrospective study showed.

Allogeneic hematopoietic stem cell transplant (HSCT) appeared to improve both disease-free and overall survival in those patients who had achieved MRD-negative complete remission, according to results of the study, which were presented at the annual meeting of the American Society of Clinical Oncology.

“Based upon our interaction testing, the potential benefit [of transplant] appears to exist in both good-risk and bad-risk patients as identified through multivariate modeling,” said study investigator Kevin Anthony Hay, MD, of Fred Hutchinson Cancer Research Center, Seattle.

In a comment on the results, Sarah Cooley, MD, noted that the benefits of allogeneic transplant were apparent regardless of whether the patients met criteria for the good-risk subgroup, which was defined by levels of lactate dehydrogenase (LDH) and platelets along with exposure to fludarabine as part of the conditioning regimen.

“I think this suggests that the goal at this point is to get patients to an MRD-negative state and to potentially curative transplant,” said Dr. Cooley, director of investigator-initiated research at Masonic Medical Center at the University of Minnesota, Minneapolis.

The retrospective analysis by Dr. Hay and his colleagues included 53 adults with relapsed or refractory ALL who had bone marrow or extramedullary disease at baseline and had received CD19 CAR T cells at or under the maximum tolerated dose at least 1 year prior to this analysis. Of that group, 45 (85%) achieved MRD-negative complete remission.

Those patients who did achieve MRD-negative complete remission had an improved median disease-free survival at 7.6 months versus 0.8 months (P less than .0001) and improved overall survival at 20.0 months versus 5.0 months (P = 0.014).

SOURCE: Hay KA. ASCO 2018, Abstract 7005.

CHICAGO – Minimal residual disease (MRD)–negative complete remission was strongly associated with improved survival outcomes in patients with B-cell acute lymphocytic leukemia (ALL) who received CD19 chimeric antigen receptor (CAR) T cells, results of a retrospective study showed.

Allogeneic hematopoietic stem cell transplant (HSCT) appeared to improve both disease-free and overall survival in those patients who had achieved MRD-negative complete remission, according to results of the study, which were presented at the annual meeting of the American Society of Clinical Oncology.

“Based upon our interaction testing, the potential benefit [of transplant] appears to exist in both good-risk and bad-risk patients as identified through multivariate modeling,” said study investigator Kevin Anthony Hay, MD, of Fred Hutchinson Cancer Research Center, Seattle.

In a comment on the results, Sarah Cooley, MD, noted that the benefits of allogeneic transplant were apparent regardless of whether the patients met criteria for the good-risk subgroup, which was defined by levels of lactate dehydrogenase (LDH) and platelets along with exposure to fludarabine as part of the conditioning regimen.

“I think this suggests that the goal at this point is to get patients to an MRD-negative state and to potentially curative transplant,” said Dr. Cooley, director of investigator-initiated research at Masonic Medical Center at the University of Minnesota, Minneapolis.

The retrospective analysis by Dr. Hay and his colleagues included 53 adults with relapsed or refractory ALL who had bone marrow or extramedullary disease at baseline and had received CD19 CAR T cells at or under the maximum tolerated dose at least 1 year prior to this analysis. Of that group, 45 (85%) achieved MRD-negative complete remission.

Those patients who did achieve MRD-negative complete remission had an improved median disease-free survival at 7.6 months versus 0.8 months (P less than .0001) and improved overall survival at 20.0 months versus 5.0 months (P = 0.014).

SOURCE: Hay KA. ASCO 2018, Abstract 7005.

CHICAGO – Minimal residual disease (MRD)–negative complete remission was strongly associated with improved survival outcomes in patients with B-cell acute lymphocytic leukemia (ALL) who received CD19 chimeric antigen receptor (CAR) T cells, results of a retrospective study showed.

Allogeneic hematopoietic stem cell transplant (HSCT) appeared to improve both disease-free and overall survival in those patients who had achieved MRD-negative complete remission, according to results of the study, which were presented at the annual meeting of the American Society of Clinical Oncology.

“Based upon our interaction testing, the potential benefit [of transplant] appears to exist in both good-risk and bad-risk patients as identified through multivariate modeling,” said study investigator Kevin Anthony Hay, MD, of Fred Hutchinson Cancer Research Center, Seattle.

In a comment on the results, Sarah Cooley, MD, noted that the benefits of allogeneic transplant were apparent regardless of whether the patients met criteria for the good-risk subgroup, which was defined by levels of lactate dehydrogenase (LDH) and platelets along with exposure to fludarabine as part of the conditioning regimen.

“I think this suggests that the goal at this point is to get patients to an MRD-negative state and to potentially curative transplant,” said Dr. Cooley, director of investigator-initiated research at Masonic Medical Center at the University of Minnesota, Minneapolis.

The retrospective analysis by Dr. Hay and his colleagues included 53 adults with relapsed or refractory ALL who had bone marrow or extramedullary disease at baseline and had received CD19 CAR T cells at or under the maximum tolerated dose at least 1 year prior to this analysis. Of that group, 45 (85%) achieved MRD-negative complete remission.

Those patients who did achieve MRD-negative complete remission had an improved median disease-free survival at 7.6 months versus 0.8 months (P less than .0001) and improved overall survival at 20.0 months versus 5.0 months (P = 0.014).

SOURCE: Hay KA. ASCO 2018, Abstract 7005.

Vials and a syringe

The US Food and Drug Association (FDA) has approved pegfilgrastim-jmdb (Fulphila™) as the first biosimilar to Neulasta®.

The agents reduce the risk of infection or the duration of febrile neutropenia in patients treated with immunosuppressive chemotherapy for non-myeloid hematologic malignancies.

The FDA approved Fulphila based on evidence that included extensive structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamic data, clinical immunogenicity data, and other clinical safety and effectiveness data.

The evidence demonstrated that Fulphila is biosimilar to Amgen’s Neulasta. The FDA, in its announcement, noted that Fulphila has been approved as a biosimilar and not as an interchangeable product.

A biosimilar is a biological product approved based on data showing it is highly similar to a biological product already approved by the FDA, termed the reference product.

A biosimilar has no clinically meaningful differences from the reference product in terms of safety, purity, and effectiveness.

Common side effects of Fulphila include bone pain and pain in extremities.

The FDA cautions that patients with a history of serious allergic reaction to human granulocyte colony-stimulating factors, such as pegfilgrastim or filgrastim products, should not take Fulphila.

Serious side effects from Fulphila include:

• rupture of the spleen
• acute respiratory distress syndrome
• serious allergic reactions including anaphylaxis
• glomerulonephritis
• leukocytosis
• capillary leak syndrome
• potential for tumor growth

Fatal sickle cell crises have also occurred with Fulphila use.

Fulphila is not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation.

The FDA is planning to release a comprehensive new plan to advance policy efforts that promote biosimilar product development, according to FDA Commissioner Scott Gotlieb, MD.

“We want to make sure that the pathway for developing biosimilar versions of approved biologics is efficient and effective, so that patients benefit from competition to existing biologics once lawful intellectual property has lapsed on these products,” he said in the announcement.

The FDA granted approval of Fulphila to Mylan GmbH. Mylan is co-developing Fulphila with Biocon.

Last fall, the agency had issued a complete response letter saying it could not approve the proposed biosimilar pending an update to the application.

The complete response letter did not raise any questions on the biosimilarity of Fulphila (investigational drug product MYL-1401H), pharmacokinetic/pharmacodynamic data, clinical data, or immunogenicity, however.

Mylan anticipates launching Fulphila in the coming weeks. 

Vials and a syringe

The US Food and Drug Association (FDA) has approved pegfilgrastim-jmdb (Fulphila™) as the first biosimilar to Neulasta®.

The agents reduce the risk of infection or the duration of febrile neutropenia in patients treated with immunosuppressive chemotherapy for non-myeloid hematologic malignancies.

The FDA approved Fulphila based on evidence that included extensive structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamic data, clinical immunogenicity data, and other clinical safety and effectiveness data.

The evidence demonstrated that Fulphila is biosimilar to Amgen’s Neulasta. The FDA, in its announcement, noted that Fulphila has been approved as a biosimilar and not as an interchangeable product.

A biosimilar is a biological product approved based on data showing it is highly similar to a biological product already approved by the FDA, termed the reference product.

A biosimilar has no clinically meaningful differences from the reference product in terms of safety, purity, and effectiveness.

Common side effects of Fulphila include bone pain and pain in extremities.

The FDA cautions that patients with a history of serious allergic reaction to human granulocyte colony-stimulating factors, such as pegfilgrastim or filgrastim products, should not take Fulphila.

Serious side effects from Fulphila include:

• rupture of the spleen
• acute respiratory distress syndrome
• serious allergic reactions including anaphylaxis
• glomerulonephritis
• leukocytosis
• capillary leak syndrome
• potential for tumor growth

Fatal sickle cell crises have also occurred with Fulphila use.

Fulphila is not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation.

The FDA is planning to release a comprehensive new plan to advance policy efforts that promote biosimilar product development, according to FDA Commissioner Scott Gotlieb, MD.

“We want to make sure that the pathway for developing biosimilar versions of approved biologics is efficient and effective, so that patients benefit from competition to existing biologics once lawful intellectual property has lapsed on these products,” he said in the announcement.

The FDA granted approval of Fulphila to Mylan GmbH. Mylan is co-developing Fulphila with Biocon.

Last fall, the agency had issued a complete response letter saying it could not approve the proposed biosimilar pending an update to the application.

The complete response letter did not raise any questions on the biosimilarity of Fulphila (investigational drug product MYL-1401H), pharmacokinetic/pharmacodynamic data, clinical data, or immunogenicity, however.

Mylan anticipates launching Fulphila in the coming weeks. 

Vials and a syringe

The US Food and Drug Association (FDA) has approved pegfilgrastim-jmdb (Fulphila™) as the first biosimilar to Neulasta®.

The agents reduce the risk of infection or the duration of febrile neutropenia in patients treated with immunosuppressive chemotherapy for non-myeloid hematologic malignancies.

The FDA approved Fulphila based on evidence that included extensive structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamic data, clinical immunogenicity data, and other clinical safety and effectiveness data.

The evidence demonstrated that Fulphila is biosimilar to Amgen’s Neulasta. The FDA, in its announcement, noted that Fulphila has been approved as a biosimilar and not as an interchangeable product.

A biosimilar is a biological product approved based on data showing it is highly similar to a biological product already approved by the FDA, termed the reference product.

A biosimilar has no clinically meaningful differences from the reference product in terms of safety, purity, and effectiveness.

Common side effects of Fulphila include bone pain and pain in extremities.

The FDA cautions that patients with a history of serious allergic reaction to human granulocyte colony-stimulating factors, such as pegfilgrastim or filgrastim products, should not take Fulphila.

Serious side effects from Fulphila include:

• rupture of the spleen
• acute respiratory distress syndrome
• serious allergic reactions including anaphylaxis
• glomerulonephritis
• leukocytosis
• capillary leak syndrome
• potential for tumor growth

Fatal sickle cell crises have also occurred with Fulphila use.

Fulphila is not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation.

The FDA is planning to release a comprehensive new plan to advance policy efforts that promote biosimilar product development, according to FDA Commissioner Scott Gotlieb, MD.

“We want to make sure that the pathway for developing biosimilar versions of approved biologics is efficient and effective, so that patients benefit from competition to existing biologics once lawful intellectual property has lapsed on these products,” he said in the announcement.

The FDA granted approval of Fulphila to Mylan GmbH. Mylan is co-developing Fulphila with Biocon.

Last fall, the agency had issued a complete response letter saying it could not approve the proposed biosimilar pending an update to the application.

The complete response letter did not raise any questions on the biosimilarity of Fulphila (investigational drug product MYL-1401H), pharmacokinetic/pharmacodynamic data, clinical data, or immunogenicity, however.

Mylan anticipates launching Fulphila in the coming weeks. 

Photo by Bill Branson

Currently, 1,120 new medicines and vaccines are being developed to treat cancer, according to a new report of the Pharmaceutical Research and Manufacturers of America (PhRMA).

And all of them, the organization states, are in clinical trials or awaiting review by the US Food and Drug Administration (FDA).

Leading the way are treatments for solid tumors, with 397 in development. Treatments for blood cancers are not far behind, with nearly 340 medicines in development: 137 for leukemias, 135 for lymphomas, and 62 for multiple myeloma.

Immuno-oncology and personalized medicine have a hand in this increase.

In the last year, according to PhRMA’s  "Medicines in Development for Cancer 2018 Report," 47 new immune-oncology treatments have been added to the development pipeline, including CAR-T therapies and checkpoint inhibitors.

This brings the total to 295 immuno-oncology medicines and vaccines in the development pipeline this year.

The report also states that about 85% of these medicines in the oncology pipeline are first-in-class.

And PhRMA attributes the approximately 73% of survival gains in cancer to the new medicines.

Despite the bright picture, PhRMA acknowledges the financial burden and medical care challenges patients encounter.

It addresses them in a new chart pack, "Cancer Medicines: Value in Context," which puts cancer costs in perspective and offers solutions for improving the current system in the United States.

The association reports the top medical financial concerns of patients to be diagnostic tests or scans (53%), prescription medicines (43%), physician office visits (39%), outpatient treatments-including radiation (37%), and surgery (36%).

Spending on cancer medicines represents about 1% of overall healthcare spending, according to the organization, with cancer medications accounting for $49.8 billion of the $3.49 trillion healthcare spending in the United States.

Cancer medicines represent about 20% of spending on cancer, PhrMA notes, and some insurance plans place treatments for certain high-cost conditions on the highest drug formulary cost-sharing tier.

And patients with the highest copay were 5 times more likely to abandon treatment than the lowest copay group, PhRMA points out.

“No patient should struggle to afford their needed treatments,” PhRMA stated in a release, “and it is important that we address patient access challenges.” 

Photo by Bill Branson

Currently, 1,120 new medicines and vaccines are being developed to treat cancer, according to a new report of the Pharmaceutical Research and Manufacturers of America (PhRMA).

And all of them, the organization states, are in clinical trials or awaiting review by the US Food and Drug Administration (FDA).

Leading the way are treatments for solid tumors, with 397 in development. Treatments for blood cancers are not far behind, with nearly 340 medicines in development: 137 for leukemias, 135 for lymphomas, and 62 for multiple myeloma.

Immuno-oncology and personalized medicine have a hand in this increase.

In the last year, according to PhRMA’s  "Medicines in Development for Cancer 2018 Report," 47 new immune-oncology treatments have been added to the development pipeline, including CAR-T therapies and checkpoint inhibitors.

This brings the total to 295 immuno-oncology medicines and vaccines in the development pipeline this year.

The report also states that about 85% of these medicines in the oncology pipeline are first-in-class.

And PhRMA attributes the approximately 73% of survival gains in cancer to the new medicines.

Despite the bright picture, PhRMA acknowledges the financial burden and medical care challenges patients encounter.

It addresses them in a new chart pack, "Cancer Medicines: Value in Context," which puts cancer costs in perspective and offers solutions for improving the current system in the United States.

The association reports the top medical financial concerns of patients to be diagnostic tests or scans (53%), prescription medicines (43%), physician office visits (39%), outpatient treatments-including radiation (37%), and surgery (36%).

Spending on cancer medicines represents about 1% of overall healthcare spending, according to the organization, with cancer medications accounting for $49.8 billion of the $3.49 trillion healthcare spending in the United States.

Cancer medicines represent about 20% of spending on cancer, PhrMA notes, and some insurance plans place treatments for certain high-cost conditions on the highest drug formulary cost-sharing tier.

And patients with the highest copay were 5 times more likely to abandon treatment than the lowest copay group, PhRMA points out.

“No patient should struggle to afford their needed treatments,” PhRMA stated in a release, “and it is important that we address patient access challenges.” 

Photo by Bill Branson

Currently, 1,120 new medicines and vaccines are being developed to treat cancer, according to a new report of the Pharmaceutical Research and Manufacturers of America (PhRMA).

And all of them, the organization states, are in clinical trials or awaiting review by the US Food and Drug Administration (FDA).

Leading the way are treatments for solid tumors, with 397 in development. Treatments for blood cancers are not far behind, with nearly 340 medicines in development: 137 for leukemias, 135 for lymphomas, and 62 for multiple myeloma.

Immuno-oncology and personalized medicine have a hand in this increase.

In the last year, according to PhRMA’s  "Medicines in Development for Cancer 2018 Report," 47 new immune-oncology treatments have been added to the development pipeline, including CAR-T therapies and checkpoint inhibitors.

This brings the total to 295 immuno-oncology medicines and vaccines in the development pipeline this year.

The report also states that about 85% of these medicines in the oncology pipeline are first-in-class.

And PhRMA attributes the approximately 73% of survival gains in cancer to the new medicines.

Despite the bright picture, PhRMA acknowledges the financial burden and medical care challenges patients encounter.

It addresses them in a new chart pack, "Cancer Medicines: Value in Context," which puts cancer costs in perspective and offers solutions for improving the current system in the United States.

The association reports the top medical financial concerns of patients to be diagnostic tests or scans (53%), prescription medicines (43%), physician office visits (39%), outpatient treatments-including radiation (37%), and surgery (36%).

Spending on cancer medicines represents about 1% of overall healthcare spending, according to the organization, with cancer medications accounting for $49.8 billion of the $3.49 trillion healthcare spending in the United States.

Cancer medicines represent about 20% of spending on cancer, PhrMA notes, and some insurance plans place treatments for certain high-cost conditions on the highest drug formulary cost-sharing tier.

And patients with the highest copay were 5 times more likely to abandon treatment than the lowest copay group, PhRMA points out.

“No patient should struggle to afford their needed treatments,” PhRMA stated in a release, “and it is important that we address patient access challenges.” 

CHICAGO – The investigational drug ivosidenib was associated with durable responses, transfusion independence, and a low rate of serious adverse events in patients with IDH1-mutated relapsed/refractory acute myeloid leukemia (AML), based on results of a phase 1 study presented at the annual meeting of the American Society of Clinical Oncology (ASCO).

Daily oral ivosidenib, which inhibits mutant IDH1 the gene that encodes for isocitrate dehydrogenase 1 and is present in 6%-10% of AML patients, was associated with a complete response rate of nearly 32%. In patients who achieved a complete response, median duration of response was 8.2 months and median overall survival was 18.8 months, Daniel A. Pollyea, MD, University of Colorado School of Medicine, Aurora, reported at the meeting.

A wide variety of study participants achieved transfusion independence, even patients who had lesser and no discernable responses, Dr. Pollyea said. “A significant minority of these patients (with lesser or no response) were able to achieve transfusion independence which is obviously a big achievement with respect to quality of life, and suggestive of the mechanism of action here with respect to differentiation.”

The conclusions of this study are “striking,” with response rates and tolerability “very similar” to results seen with the IDH2 inhibitor enasidenib, said Eunice S. Wang, MD, of Roswell Park Comprehensive Cancer Center, Buffalo, N.Y.

Ivosidenib is “likely to become the new standard of care treatment” for IDH1-mutant patients in the relapsed-refractory setting based on the data presented at ASCO, Dr. Wang said in a presentation commenting on the results.

“Given the development of ivosidenib and enasidenib, I think we should all carefully consider whether testing of IDH1 and IDH2 mutational status should also become standard of care in all relapsed and refractory patients, in order to offer them these novel and highly effective as well as well-tolerated targeted therapies,” she said.

Enasidenib was approved by the U.S. Food and Drug Administration (FDA) in 2017 for relapsed or refractory AML with an IDH2 mutation.

Here at ASCO, Dr. Pollyea reported results based on 179 patients with relapsed/refractory IDH1-mutant AML who received 500 mg of ivosidenib daily.

The overall response rate was 41.9% (75 patients), he said. The rate of complete remission (CR) or CR with partial hematologic recovery (CRh) was 31.8% (57 patients), with a median of 2.0 months to CR/CRh and a median duration of CR/CRh of 8.2 months, he said.

Grade 3 or greater leukocytosis was seen in 8% of patients, and grade 3 or greater QT prolongation was seen in 10% of patients, Dr. Pollyea reported.

IHD differentiation syndrome of any grade was seen in 19 patients (10.6%), and about half of those cases (5%) were grade 3 or greater. However, cases were managed with supportive care, and there were no dose reductions, permanent treatment discontinuations, or deaths due to the condition, Dr. Pollyea said.

Moreover, the majority of those patients (10 out of 19) went on to have a response. “Supportive care and continued treatment can allow for patients ultimately to respond who are experiencing differentiation syndrome,” Dr. Pollyea said.

Results of the phase 1 study were published simultaneously in the New England Journal of Medicine.The trial was sponsored by Agios. Dr. Pollyea reported disclosures related to Agios, as well as Abbvie, argenx, Celgene, Celyad, Curis, Pfizer, and Servier.

SOURCE: Pollyea DA, et al. J Clin Oncol36, 2018 (suppl; abstr 7000).

CHICAGO – The investigational drug ivosidenib was associated with durable responses, transfusion independence, and a low rate of serious adverse events in patients with IDH1-mutated relapsed/refractory acute myeloid leukemia (AML), based on results of a phase 1 study presented at the annual meeting of the American Society of Clinical Oncology (ASCO).

Daily oral ivosidenib, which inhibits mutant IDH1 the gene that encodes for isocitrate dehydrogenase 1 and is present in 6%-10% of AML patients, was associated with a complete response rate of nearly 32%. In patients who achieved a complete response, median duration of response was 8.2 months and median overall survival was 18.8 months, Daniel A. Pollyea, MD, University of Colorado School of Medicine, Aurora, reported at the meeting.

A wide variety of study participants achieved transfusion independence, even patients who had lesser and no discernable responses, Dr. Pollyea said. “A significant minority of these patients (with lesser or no response) were able to achieve transfusion independence which is obviously a big achievement with respect to quality of life, and suggestive of the mechanism of action here with respect to differentiation.”

The conclusions of this study are “striking,” with response rates and tolerability “very similar” to results seen with the IDH2 inhibitor enasidenib, said Eunice S. Wang, MD, of Roswell Park Comprehensive Cancer Center, Buffalo, N.Y.

Ivosidenib is “likely to become the new standard of care treatment” for IDH1-mutant patients in the relapsed-refractory setting based on the data presented at ASCO, Dr. Wang said in a presentation commenting on the results.

“Given the development of ivosidenib and enasidenib, I think we should all carefully consider whether testing of IDH1 and IDH2 mutational status should also become standard of care in all relapsed and refractory patients, in order to offer them these novel and highly effective as well as well-tolerated targeted therapies,” she said.

Enasidenib was approved by the U.S. Food and Drug Administration (FDA) in 2017 for relapsed or refractory AML with an IDH2 mutation.

Here at ASCO, Dr. Pollyea reported results based on 179 patients with relapsed/refractory IDH1-mutant AML who received 500 mg of ivosidenib daily.

The overall response rate was 41.9% (75 patients), he said. The rate of complete remission (CR) or CR with partial hematologic recovery (CRh) was 31.8% (57 patients), with a median of 2.0 months to CR/CRh and a median duration of CR/CRh of 8.2 months, he said.

Grade 3 or greater leukocytosis was seen in 8% of patients, and grade 3 or greater QT prolongation was seen in 10% of patients, Dr. Pollyea reported.

IHD differentiation syndrome of any grade was seen in 19 patients (10.6%), and about half of those cases (5%) were grade 3 or greater. However, cases were managed with supportive care, and there were no dose reductions, permanent treatment discontinuations, or deaths due to the condition, Dr. Pollyea said.

Moreover, the majority of those patients (10 out of 19) went on to have a response. “Supportive care and continued treatment can allow for patients ultimately to respond who are experiencing differentiation syndrome,” Dr. Pollyea said.

Results of the phase 1 study were published simultaneously in the New England Journal of Medicine.The trial was sponsored by Agios. Dr. Pollyea reported disclosures related to Agios, as well as Abbvie, argenx, Celgene, Celyad, Curis, Pfizer, and Servier.

SOURCE: Pollyea DA, et al. J Clin Oncol36, 2018 (suppl; abstr 7000).

CHICAGO – The investigational drug ivosidenib was associated with durable responses, transfusion independence, and a low rate of serious adverse events in patients with IDH1-mutated relapsed/refractory acute myeloid leukemia (AML), based on results of a phase 1 study presented at the annual meeting of the American Society of Clinical Oncology (ASCO).

Daily oral ivosidenib, which inhibits mutant IDH1 the gene that encodes for isocitrate dehydrogenase 1 and is present in 6%-10% of AML patients, was associated with a complete response rate of nearly 32%. In patients who achieved a complete response, median duration of response was 8.2 months and median overall survival was 18.8 months, Daniel A. Pollyea, MD, University of Colorado School of Medicine, Aurora, reported at the meeting.

A wide variety of study participants achieved transfusion independence, even patients who had lesser and no discernable responses, Dr. Pollyea said. “A significant minority of these patients (with lesser or no response) were able to achieve transfusion independence which is obviously a big achievement with respect to quality of life, and suggestive of the mechanism of action here with respect to differentiation.”

The conclusions of this study are “striking,” with response rates and tolerability “very similar” to results seen with the IDH2 inhibitor enasidenib, said Eunice S. Wang, MD, of Roswell Park Comprehensive Cancer Center, Buffalo, N.Y.

Ivosidenib is “likely to become the new standard of care treatment” for IDH1-mutant patients in the relapsed-refractory setting based on the data presented at ASCO, Dr. Wang said in a presentation commenting on the results.

“Given the development of ivosidenib and enasidenib, I think we should all carefully consider whether testing of IDH1 and IDH2 mutational status should also become standard of care in all relapsed and refractory patients, in order to offer them these novel and highly effective as well as well-tolerated targeted therapies,” she said.

Enasidenib was approved by the U.S. Food and Drug Administration (FDA) in 2017 for relapsed or refractory AML with an IDH2 mutation.

Here at ASCO, Dr. Pollyea reported results based on 179 patients with relapsed/refractory IDH1-mutant AML who received 500 mg of ivosidenib daily.

The overall response rate was 41.9% (75 patients), he said. The rate of complete remission (CR) or CR with partial hematologic recovery (CRh) was 31.8% (57 patients), with a median of 2.0 months to CR/CRh and a median duration of CR/CRh of 8.2 months, he said.

Grade 3 or greater leukocytosis was seen in 8% of patients, and grade 3 or greater QT prolongation was seen in 10% of patients, Dr. Pollyea reported.

IHD differentiation syndrome of any grade was seen in 19 patients (10.6%), and about half of those cases (5%) were grade 3 or greater. However, cases were managed with supportive care, and there were no dose reductions, permanent treatment discontinuations, or deaths due to the condition, Dr. Pollyea said.

Moreover, the majority of those patients (10 out of 19) went on to have a response. “Supportive care and continued treatment can allow for patients ultimately to respond who are experiencing differentiation syndrome,” Dr. Pollyea said.

Results of the phase 1 study were published simultaneously in the New England Journal of Medicine.The trial was sponsored by Agios. Dr. Pollyea reported disclosures related to Agios, as well as Abbvie, argenx, Celgene, Celyad, Curis, Pfizer, and Servier.

SOURCE: Pollyea DA, et al. J Clin Oncol36, 2018 (suppl; abstr 7000).

Credit: Anatomography

A 6-year prospective study from the Canadian STOPP investigators revealed that following treatment for acute lymphoblastic leukemia (ALL), approximately 1 out of 3 children experiences vertebral fractures (VF) and 1 out of 5 children shows non-VF.

Glucocorticoid use and vertebral fractures at diagnosis emerged as significant predictive factors.

Investigators reported a cumulative incidence of 32.5% for vertebral fractures (VF) following treatment and 23.0% for non-VF after 6 years.

Thirty-nine percent of children with VF were asymptomatic.

“The osteotoxicity of leukemia and its treatment are underscored by the observation that the non-VF incidence was more than 2.5 times higher than the general pediatric population,” the study authors wrote, “whereas the VF incidence was increased more than 2000 times.”

The STOPP investigators—the Steroid-Associated Osteoporosis in the Pediatric Population Consortium—published their findings in the Journal of Bone and Mineral Research.

To document the incidence and predictors of fractures and profile who is at greatest risk, the STOPP investigators enrolled 186 children who were diagnosed and treated at 10 children’s hospitals across Canada between 2005 and 2007.

Median age at diagnosis was 5.3 years, median duration of follow-up was 6 years, and 38.1% were boys.

Approximately 4 out of 5 children were treated with Children’s Oncology Group protocols and 1 out of 5 was treated with the Dana-Farber protocols.

In girls, glucocorticoid exposure was 7.0 g/m² and in boys it was 8.9 g/m².

The entire cohort received 54.3% of the total cumulative glucocorticoid dose in the first year and 83.1% in the second year.

For VF, incidence at baseline was 15.1%. Skeletal fractures at any site were reported in 36% of the children over the 6-year period, 71% occurring during the first 2 years. No VF was reported in the sixth year.

Of 38 children with VF, 32 sustained at least 1 VF in the first 2 years and 77% occurred while on therapy or within 6 months of the last glucocorticoid dose. None of the children had disease relapse.

Non-VF were reported in 1.6% of children at baseline; incidence peaked at years 2 (5.4%) and 5 (4.8%) and none occurred in the sixth year.

Thirty-one non-VFs were reported in 26 children; 18 occurred in the first 2 years and 23 occurred on therapy or within 6 months of the last glucocorticoid dose.

The STOPP investigators showed that glucocorticoid exposure, VF, and low spine bone mineral density Z-scores at baseline were significant predictors for risk of VF.

“[This] observation suggests the importance of baseline spine phenotype (both VF and low lumbar spine bone mineral density) in signaling the potential for future bone morbidity,” the STOPP investigators note.

“In revealing that vertebral fractures are frequent in children with ALL on chemotherapy, and that older children and those with more severe collapse are at risk for residual vertebral deformities, strategies to prevent vertebral fractures in those at greatest risk for permanent sequelae now merit further study,” said lead author Leanne Ward, MD, of the University of Ottawa, Canada, in a statement.

The study was primarily supported by an operating grant from the Canadian Institutes for Health Research (CIHR) with additional funding from a CIHR New Investigator Award, a Canadian Child Health Clinician Scientist Career Enhancement Award, a University of Ottawa Research Chair Award, a Children’s Hospital of Eastern Ontario (CHEO) Research Institute Capacity Building Award, and the CHEO Departments of Pediatrics and Surgery. This work was also supported by the University of Alberta Women and Children’s Health Research Institute. 

Credit: Anatomography

A 6-year prospective study from the Canadian STOPP investigators revealed that following treatment for acute lymphoblastic leukemia (ALL), approximately 1 out of 3 children experiences vertebral fractures (VF) and 1 out of 5 children shows non-VF.

Glucocorticoid use and vertebral fractures at diagnosis emerged as significant predictive factors.

Investigators reported a cumulative incidence of 32.5% for vertebral fractures (VF) following treatment and 23.0% for non-VF after 6 years.

Thirty-nine percent of children with VF were asymptomatic.

“The osteotoxicity of leukemia and its treatment are underscored by the observation that the non-VF incidence was more than 2.5 times higher than the general pediatric population,” the study authors wrote, “whereas the VF incidence was increased more than 2000 times.”

The STOPP investigators—the Steroid-Associated Osteoporosis in the Pediatric Population Consortium—published their findings in the Journal of Bone and Mineral Research.

To document the incidence and predictors of fractures and profile who is at greatest risk, the STOPP investigators enrolled 186 children who were diagnosed and treated at 10 children’s hospitals across Canada between 2005 and 2007.

Median age at diagnosis was 5.3 years, median duration of follow-up was 6 years, and 38.1% were boys.

Approximately 4 out of 5 children were treated with Children’s Oncology Group protocols and 1 out of 5 was treated with the Dana-Farber protocols.

In girls, glucocorticoid exposure was 7.0 g/m² and in boys it was 8.9 g/m².

The entire cohort received 54.3% of the total cumulative glucocorticoid dose in the first year and 83.1% in the second year.

For VF, incidence at baseline was 15.1%. Skeletal fractures at any site were reported in 36% of the children over the 6-year period, 71% occurring during the first 2 years. No VF was reported in the sixth year.

Of 38 children with VF, 32 sustained at least 1 VF in the first 2 years and 77% occurred while on therapy or within 6 months of the last glucocorticoid dose. None of the children had disease relapse.

Non-VF were reported in 1.6% of children at baseline; incidence peaked at years 2 (5.4%) and 5 (4.8%) and none occurred in the sixth year.

Thirty-one non-VFs were reported in 26 children; 18 occurred in the first 2 years and 23 occurred on therapy or within 6 months of the last glucocorticoid dose.

The STOPP investigators showed that glucocorticoid exposure, VF, and low spine bone mineral density Z-scores at baseline were significant predictors for risk of VF.

“[This] observation suggests the importance of baseline spine phenotype (both VF and low lumbar spine bone mineral density) in signaling the potential for future bone morbidity,” the STOPP investigators note.

“In revealing that vertebral fractures are frequent in children with ALL on chemotherapy, and that older children and those with more severe collapse are at risk for residual vertebral deformities, strategies to prevent vertebral fractures in those at greatest risk for permanent sequelae now merit further study,” said lead author Leanne Ward, MD, of the University of Ottawa, Canada, in a statement.

The study was primarily supported by an operating grant from the Canadian Institutes for Health Research (CIHR) with additional funding from a CIHR New Investigator Award, a Canadian Child Health Clinician Scientist Career Enhancement Award, a University of Ottawa Research Chair Award, a Children’s Hospital of Eastern Ontario (CHEO) Research Institute Capacity Building Award, and the CHEO Departments of Pediatrics and Surgery. This work was also supported by the University of Alberta Women and Children’s Health Research Institute. 

Credit: Anatomography

A 6-year prospective study from the Canadian STOPP investigators revealed that following treatment for acute lymphoblastic leukemia (ALL), approximately 1 out of 3 children experiences vertebral fractures (VF) and 1 out of 5 children shows non-VF.

Glucocorticoid use and vertebral fractures at diagnosis emerged as significant predictive factors.

Investigators reported a cumulative incidence of 32.5% for vertebral fractures (VF) following treatment and 23.0% for non-VF after 6 years.

Thirty-nine percent of children with VF were asymptomatic.

“The osteotoxicity of leukemia and its treatment are underscored by the observation that the non-VF incidence was more than 2.5 times higher than the general pediatric population,” the study authors wrote, “whereas the VF incidence was increased more than 2000 times.”

The STOPP investigators—the Steroid-Associated Osteoporosis in the Pediatric Population Consortium—published their findings in the Journal of Bone and Mineral Research.

To document the incidence and predictors of fractures and profile who is at greatest risk, the STOPP investigators enrolled 186 children who were diagnosed and treated at 10 children’s hospitals across Canada between 2005 and 2007.

Median age at diagnosis was 5.3 years, median duration of follow-up was 6 years, and 38.1% were boys.

Approximately 4 out of 5 children were treated with Children’s Oncology Group protocols and 1 out of 5 was treated with the Dana-Farber protocols.

In girls, glucocorticoid exposure was 7.0 g/m² and in boys it was 8.9 g/m².

The entire cohort received 54.3% of the total cumulative glucocorticoid dose in the first year and 83.1% in the second year.

For VF, incidence at baseline was 15.1%. Skeletal fractures at any site were reported in 36% of the children over the 6-year period, 71% occurring during the first 2 years. No VF was reported in the sixth year.

Of 38 children with VF, 32 sustained at least 1 VF in the first 2 years and 77% occurred while on therapy or within 6 months of the last glucocorticoid dose. None of the children had disease relapse.

Non-VF were reported in 1.6% of children at baseline; incidence peaked at years 2 (5.4%) and 5 (4.8%) and none occurred in the sixth year.

Thirty-one non-VFs were reported in 26 children; 18 occurred in the first 2 years and 23 occurred on therapy or within 6 months of the last glucocorticoid dose.

The STOPP investigators showed that glucocorticoid exposure, VF, and low spine bone mineral density Z-scores at baseline were significant predictors for risk of VF.

“[This] observation suggests the importance of baseline spine phenotype (both VF and low lumbar spine bone mineral density) in signaling the potential for future bone morbidity,” the STOPP investigators note.

“In revealing that vertebral fractures are frequent in children with ALL on chemotherapy, and that older children and those with more severe collapse are at risk for residual vertebral deformities, strategies to prevent vertebral fractures in those at greatest risk for permanent sequelae now merit further study,” said lead author Leanne Ward, MD, of the University of Ottawa, Canada, in a statement.

The study was primarily supported by an operating grant from the Canadian Institutes for Health Research (CIHR) with additional funding from a CIHR New Investigator Award, a Canadian Child Health Clinician Scientist Career Enhancement Award, a University of Ottawa Research Chair Award, a Children’s Hospital of Eastern Ontario (CHEO) Research Institute Capacity Building Award, and the CHEO Departments of Pediatrics and Surgery. This work was also supported by the University of Alberta Women and Children’s Health Research Institute. 

AML cells

The US Food and Drug Administration (FDA) has granted priority review to gilteritinib for the treatment of adult patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) who have a FLT3 mutation.

At present, no FLT3-targeting agents are approved for the treatment of R/R FLT3-mutation-positive AML, according to Astellas, the developer of the drug.

The FDA previously granted gilteritinib orphan drug designation and fast track designation.

The European Commission (EC) also granted gilteritinib orphan designation and the Japan Ministry of Health, Labor and Welfare (MHLW) did likewise.

Gilteritinib has demonstrated inhibitory activity against FLT3 internal tandem duplication (ITD) and FLT tyrosine kinase domain (TKD) mutation. These 2 FLT3 mutations are present in approximately 1/3 of AML patients.

The priority review for the new drug application is based on the ongoing phase 3 ADMIRAL trial.

The FDA aims to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

The agency grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

The goal date for a decision by the FDA is the end of November.

ADMIRAL trial (NCT02421939)

This open-label multicenter randomized study compares gilteritinib with salvage chemotherapy in adult patients with FLT3 mutations who are refractory to or have relapsed after first-line AML therapy.

The study has enrolled 371 patients with FLT3 mutations present in bone marrow or whole blood, as determined by a central lab.

Patients were randomized in a 2:1 ratio to receive gilteritinib (120 mg) or salvage chemotherapy.

Salvage chemotherapy could consist of low-dose cytarabine, azacitidine, MEC (mitoxantrone, etoposide, cytarabine) induction chemotherapy, or FLAG-IDA (fludarabine, cytarabine, and granulocyte colony-stimulating factor [G-CSF] with idarubicin) induction chemotherapy.

The primary endpoints of the study are overall survival and complete remission or complete remission with partial hematologic recovery.

Secondary endpoints include event-free survival, complete remission rate, leukemia-free survival, duration of remission, transplantation rate, fatigue inventory, among other outcomes.

The study is estimated to be completed in October for its primary endpoint and February 2020 for the entire study.  

AML cells

The US Food and Drug Administration (FDA) has granted priority review to gilteritinib for the treatment of adult patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) who have a FLT3 mutation.

At present, no FLT3-targeting agents are approved for the treatment of R/R FLT3-mutation-positive AML, according to Astellas, the developer of the drug.

The FDA previously granted gilteritinib orphan drug designation and fast track designation.

The European Commission (EC) also granted gilteritinib orphan designation and the Japan Ministry of Health, Labor and Welfare (MHLW) did likewise.

Gilteritinib has demonstrated inhibitory activity against FLT3 internal tandem duplication (ITD) and FLT tyrosine kinase domain (TKD) mutation. These 2 FLT3 mutations are present in approximately 1/3 of AML patients.

The priority review for the new drug application is based on the ongoing phase 3 ADMIRAL trial.

The FDA aims to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

The agency grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

The goal date for a decision by the FDA is the end of November.

ADMIRAL trial (NCT02421939)

This open-label multicenter randomized study compares gilteritinib with salvage chemotherapy in adult patients with FLT3 mutations who are refractory to or have relapsed after first-line AML therapy.

The study has enrolled 371 patients with FLT3 mutations present in bone marrow or whole blood, as determined by a central lab.

Patients were randomized in a 2:1 ratio to receive gilteritinib (120 mg) or salvage chemotherapy.

Salvage chemotherapy could consist of low-dose cytarabine, azacitidine, MEC (mitoxantrone, etoposide, cytarabine) induction chemotherapy, or FLAG-IDA (fludarabine, cytarabine, and granulocyte colony-stimulating factor [G-CSF] with idarubicin) induction chemotherapy.

The primary endpoints of the study are overall survival and complete remission or complete remission with partial hematologic recovery.

Secondary endpoints include event-free survival, complete remission rate, leukemia-free survival, duration of remission, transplantation rate, fatigue inventory, among other outcomes.

The study is estimated to be completed in October for its primary endpoint and February 2020 for the entire study.  

AML cells

The US Food and Drug Administration (FDA) has granted priority review to gilteritinib for the treatment of adult patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) who have a FLT3 mutation.

At present, no FLT3-targeting agents are approved for the treatment of R/R FLT3-mutation-positive AML, according to Astellas, the developer of the drug.

The FDA previously granted gilteritinib orphan drug designation and fast track designation.

The European Commission (EC) also granted gilteritinib orphan designation and the Japan Ministry of Health, Labor and Welfare (MHLW) did likewise.

Gilteritinib has demonstrated inhibitory activity against FLT3 internal tandem duplication (ITD) and FLT tyrosine kinase domain (TKD) mutation. These 2 FLT3 mutations are present in approximately 1/3 of AML patients.

The priority review for the new drug application is based on the ongoing phase 3 ADMIRAL trial.

The FDA aims to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

The agency grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

The goal date for a decision by the FDA is the end of November.

ADMIRAL trial (NCT02421939)

This open-label multicenter randomized study compares gilteritinib with salvage chemotherapy in adult patients with FLT3 mutations who are refractory to or have relapsed after first-line AML therapy.

The study has enrolled 371 patients with FLT3 mutations present in bone marrow or whole blood, as determined by a central lab.

Patients were randomized in a 2:1 ratio to receive gilteritinib (120 mg) or salvage chemotherapy.

Salvage chemotherapy could consist of low-dose cytarabine, azacitidine, MEC (mitoxantrone, etoposide, cytarabine) induction chemotherapy, or FLAG-IDA (fludarabine, cytarabine, and granulocyte colony-stimulating factor [G-CSF] with idarubicin) induction chemotherapy.

The primary endpoints of the study are overall survival and complete remission or complete remission with partial hematologic recovery.

Secondary endpoints include event-free survival, complete remission rate, leukemia-free survival, duration of remission, transplantation rate, fatigue inventory, among other outcomes.

The study is estimated to be completed in October for its primary endpoint and February 2020 for the entire study.  

The Food and Drug Administration has granted priority review to an FMS-like tyrosine kinase 3 (FLT3)–targeting agent for the treatment of adults with relapsed or refractory acute myeloid leukemia (AML).

Astellas Pharma is seeking approval for gilteritinib (ASP2215) for adults with FLT3 mutation–positive AML. If approved, it would be the first FLT3 inhibitor available for this indication.

The application is based on the ongoing ADMIRAL trial, a phase 3, open-label, randomized study of gilteritinib versus salvage chemotherapy. The trial is designed to enroll 369 patients with FLT3 mutations present in bone marrow or whole blood who are refractory or have relapsed on first-line therapy. The primary endpoints are overall survival and rates of complete remission and complete remission with partial hematologic recovery.

The FDA has set Nov. 29 as a target date for reaching a decision on approval of the drug.

[email protected]

The Food and Drug Administration has granted priority review to an FMS-like tyrosine kinase 3 (FLT3)–targeting agent for the treatment of adults with relapsed or refractory acute myeloid leukemia (AML).

Astellas Pharma is seeking approval for gilteritinib (ASP2215) for adults with FLT3 mutation–positive AML. If approved, it would be the first FLT3 inhibitor available for this indication.

The application is based on the ongoing ADMIRAL trial, a phase 3, open-label, randomized study of gilteritinib versus salvage chemotherapy. The trial is designed to enroll 369 patients with FLT3 mutations present in bone marrow or whole blood who are refractory or have relapsed on first-line therapy. The primary endpoints are overall survival and rates of complete remission and complete remission with partial hematologic recovery.

The FDA has set Nov. 29 as a target date for reaching a decision on approval of the drug.

[email protected]

The Food and Drug Administration has granted priority review to an FMS-like tyrosine kinase 3 (FLT3)–targeting agent for the treatment of adults with relapsed or refractory acute myeloid leukemia (AML).

Astellas Pharma is seeking approval for gilteritinib (ASP2215) for adults with FLT3 mutation–positive AML. If approved, it would be the first FLT3 inhibitor available for this indication.

The application is based on the ongoing ADMIRAL trial, a phase 3, open-label, randomized study of gilteritinib versus salvage chemotherapy. The trial is designed to enroll 369 patients with FLT3 mutations present in bone marrow or whole blood who are refractory or have relapsed on first-line therapy. The primary endpoints are overall survival and rates of complete remission and complete remission with partial hematologic recovery.

The FDA has set Nov. 29 as a target date for reaching a decision on approval of the drug.

[email protected]

Photo by Petr Kratochvil

Childhood acute lymphoblastic leukemia (ALL) may be preventable, according to a researcher.

Mel Greaves, PhD, of The Institute of Cancer Research in London, UK, reviewed more than 30 years of research and concluded that ALL develops in 2 steps—genetic mutation before birth and further genetic change after birth triggered by infection.

The evidence suggests that infection early in life is beneficial to prime the immune system, but later infection without earlier priming can trigger ALL.

So priming the immune system in the first year of life could potentially prevent childhood ALL, according to Dr Greaves.

He outlined this theory in Nature Reviews Cancer.

Dr Greaves compiled more than 30 years of research into genetics, cell biology, immunology, epidemiology, and animal modelling of ALL.

The evidence led him to conclude that ALL begins with a genetic mutation that occurs before birth and predisposes a child to leukemia.

The disease is triggered later, in childhood, by exposure to one or more common infections. This primarily occurs in children who experienced “clean” childhoods in their first year of life, without much interaction with other infants or older children.

Dr Greaves challenged previous reports of possible environmental causes for ALL, such as ionizing radiation, electromagnetic waves, or man-made chemicals. He argued that none of these reports are supported by robust evidence.

Instead, he believes there is strong evidence suggesting that infection later in childhood, in the absence of earlier priming, can trigger ALL.

Dr Greaves’ studies of identical twins with ALL showed that 2 mutations were required for ALL development. The first arises in one twin in the womb but produces a population of pre-malignant cells that spread to the other twin via their shared blood supply. The second mutation arises after birth and is different in the twins.

Population studies and animal experiments suggest this second genetic hit can be triggered by infection, probably by a range of common viruses and bacteria. In one unique cluster of cases investigated by Dr Greaves and his colleagues, all cases were infected with flu virus.

In other work, researchers engineered mice with an active leukemia-initiating gene. When the team moved the mice from an ultra-clean, germ-free environment to one that had common microbes, the mice developed ALL.

Population studies have indicated that early exposure to infection in infancy, such as via day care attendance and breast feeding, can protect against ALL, probably by priming the immune system. This suggests childhood ALL may be preventable.

Dr Greaves is now investigating whether earlier exposure to harmless microbes could prevent leukemia in mice.

“I have spent more than 40 years researching childhood leukemia, and, over that time, there has been huge progress in our understanding of its biology and its treatment . . . ,” Dr Greaves said. “But it has always struck me that something big was missing, a gap in our knowledge [that failed to explain] why or how otherwise healthy children develop leukemia and whether this cancer is preventable.”

“This body of research is a culmination of decades of work and at last provides a credible explanation for how the major type of childhood leukemia develops. The research strongly suggests that ALL has a clear biological cause and is triggered by a variety of infections in predisposed children whose immune systems have not been properly primed. It also busts some persistent myths about the causes of leukemia, such as the damaging but unsubstantiated claims that the disease is commonly caused by exposure to electro-magnetic waves or pollution.”

“I hope this research will have a real impact on the lives of children. The most important implication is that most cases of childhood leukemia are likely to be preventable. It might be done in the same way that is currently under consideration for autoimmune disease or allergies, perhaps with simple and safe interventions to expose infants to a variety of common and harmless ‘bugs.’”

Photo by Petr Kratochvil

Childhood acute lymphoblastic leukemia (ALL) may be preventable, according to a researcher.

Mel Greaves, PhD, of The Institute of Cancer Research in London, UK, reviewed more than 30 years of research and concluded that ALL develops in 2 steps—genetic mutation before birth and further genetic change after birth triggered by infection.

The evidence suggests that infection early in life is beneficial to prime the immune system, but later infection without earlier priming can trigger ALL.

So priming the immune system in the first year of life could potentially prevent childhood ALL, according to Dr Greaves.

He outlined this theory in Nature Reviews Cancer.

Dr Greaves compiled more than 30 years of research into genetics, cell biology, immunology, epidemiology, and animal modelling of ALL.

The evidence led him to conclude that ALL begins with a genetic mutation that occurs before birth and predisposes a child to leukemia.

The disease is triggered later, in childhood, by exposure to one or more common infections. This primarily occurs in children who experienced “clean” childhoods in their first year of life, without much interaction with other infants or older children.

Dr Greaves challenged previous reports of possible environmental causes for ALL, such as ionizing radiation, electromagnetic waves, or man-made chemicals. He argued that none of these reports are supported by robust evidence.

Instead, he believes there is strong evidence suggesting that infection later in childhood, in the absence of earlier priming, can trigger ALL.

Dr Greaves’ studies of identical twins with ALL showed that 2 mutations were required for ALL development. The first arises in one twin in the womb but produces a population of pre-malignant cells that spread to the other twin via their shared blood supply. The second mutation arises after birth and is different in the twins.

Population studies and animal experiments suggest this second genetic hit can be triggered by infection, probably by a range of common viruses and bacteria. In one unique cluster of cases investigated by Dr Greaves and his colleagues, all cases were infected with flu virus.

In other work, researchers engineered mice with an active leukemia-initiating gene. When the team moved the mice from an ultra-clean, germ-free environment to one that had common microbes, the mice developed ALL.

Population studies have indicated that early exposure to infection in infancy, such as via day care attendance and breast feeding, can protect against ALL, probably by priming the immune system. This suggests childhood ALL may be preventable.

Dr Greaves is now investigating whether earlier exposure to harmless microbes could prevent leukemia in mice.

“I have spent more than 40 years researching childhood leukemia, and, over that time, there has been huge progress in our understanding of its biology and its treatment . . . ,” Dr Greaves said. “But it has always struck me that something big was missing, a gap in our knowledge [that failed to explain] why or how otherwise healthy children develop leukemia and whether this cancer is preventable.”

“This body of research is a culmination of decades of work and at last provides a credible explanation for how the major type of childhood leukemia develops. The research strongly suggests that ALL has a clear biological cause and is triggered by a variety of infections in predisposed children whose immune systems have not been properly primed. It also busts some persistent myths about the causes of leukemia, such as the damaging but unsubstantiated claims that the disease is commonly caused by exposure to electro-magnetic waves or pollution.”

“I hope this research will have a real impact on the lives of children. The most important implication is that most cases of childhood leukemia are likely to be preventable. It might be done in the same way that is currently under consideration for autoimmune disease or allergies, perhaps with simple and safe interventions to expose infants to a variety of common and harmless ‘bugs.’”

Photo by Petr Kratochvil

Childhood acute lymphoblastic leukemia (ALL) may be preventable, according to a researcher.

Mel Greaves, PhD, of The Institute of Cancer Research in London, UK, reviewed more than 30 years of research and concluded that ALL develops in 2 steps—genetic mutation before birth and further genetic change after birth triggered by infection.

The evidence suggests that infection early in life is beneficial to prime the immune system, but later infection without earlier priming can trigger ALL.

So priming the immune system in the first year of life could potentially prevent childhood ALL, according to Dr Greaves.

He outlined this theory in Nature Reviews Cancer.

Dr Greaves compiled more than 30 years of research into genetics, cell biology, immunology, epidemiology, and animal modelling of ALL.

The evidence led him to conclude that ALL begins with a genetic mutation that occurs before birth and predisposes a child to leukemia.

The disease is triggered later, in childhood, by exposure to one or more common infections. This primarily occurs in children who experienced “clean” childhoods in their first year of life, without much interaction with other infants or older children.

Dr Greaves challenged previous reports of possible environmental causes for ALL, such as ionizing radiation, electromagnetic waves, or man-made chemicals. He argued that none of these reports are supported by robust evidence.

Instead, he believes there is strong evidence suggesting that infection later in childhood, in the absence of earlier priming, can trigger ALL.

Dr Greaves’ studies of identical twins with ALL showed that 2 mutations were required for ALL development. The first arises in one twin in the womb but produces a population of pre-malignant cells that spread to the other twin via their shared blood supply. The second mutation arises after birth and is different in the twins.

Population studies and animal experiments suggest this second genetic hit can be triggered by infection, probably by a range of common viruses and bacteria. In one unique cluster of cases investigated by Dr Greaves and his colleagues, all cases were infected with flu virus.

In other work, researchers engineered mice with an active leukemia-initiating gene. When the team moved the mice from an ultra-clean, germ-free environment to one that had common microbes, the mice developed ALL.

Population studies have indicated that early exposure to infection in infancy, such as via day care attendance and breast feeding, can protect against ALL, probably by priming the immune system. This suggests childhood ALL may be preventable.

Dr Greaves is now investigating whether earlier exposure to harmless microbes could prevent leukemia in mice.

“I have spent more than 40 years researching childhood leukemia, and, over that time, there has been huge progress in our understanding of its biology and its treatment . . . ,” Dr Greaves said. “But it has always struck me that something big was missing, a gap in our knowledge [that failed to explain] why or how otherwise healthy children develop leukemia and whether this cancer is preventable.”

“This body of research is a culmination of decades of work and at last provides a credible explanation for how the major type of childhood leukemia develops. The research strongly suggests that ALL has a clear biological cause and is triggered by a variety of infections in predisposed children whose immune systems have not been properly primed. It also busts some persistent myths about the causes of leukemia, such as the damaging but unsubstantiated claims that the disease is commonly caused by exposure to electro-magnetic waves or pollution.”

“I hope this research will have a real impact on the lives of children. The most important implication is that most cases of childhood leukemia are likely to be preventable. It might be done in the same way that is currently under consideration for autoimmune disease or allergies, perhaps with simple and safe interventions to expose infants to a variety of common and harmless ‘bugs.’”

Image by Lance Liotta

A signaling protein may be a “potent” therapeutic target for acute myeloid leukemia (AML), according to a paper published in the Journal of Experimental Medicine.

The protein, interleukin-1 receptor accessory protein (IL1RAP), is often highly expressed on the surface of leukemic stem cells (LSCs) but largely absent from normal hematopoietic stem cells.

Despite this, it wasn’t known whether LSCs require IL1RAP to survive and proliferate and whether inhibiting IL1RAP could be a successful way to treat AML.

Ulrich Steidl, MD, PhD, of Albert Einstein College of Medicine in Bronx, New York, and his colleagues conducted research to find out.

The team found that targeting IL1RAP via RNA interference, genetic deletion, or antibodies induced the death of AML cells, including LSCs, in vitro. These effects were seen in the absence of immune effector cells, indicating that AML cells intrinsically depend on IL1RAP.

In contrast, antibodies targeting IL1RAP had no effect on the growth and survival of normal hematopoietic cells.

In mice, IL1RAP antibody treatment inhibited the proliferation of AML cells without causing any negative side effects.

The researchers also found that IL1RAP’s role in AML is not restricted to the IL-1 receptor pathway.

The team found that IL1RAP enhances the activity of 2 other membrane receptor proteins, FLT3 and c-KIT, which are known to stimulate the proliferation of LSCs when activated by their ligands. IL1RAP antibodies inhibited the ability of these ligands to induce proliferation in AML cells.

“Our findings show that IL1RAP can amplify multiple key pathways in AML, demonstrating a much broader role for this protein in disease pathogenesis than previously appreciated,” Dr Steidl noted.

“Importantly, as IL1RAP is also overexpressed in the stem cells of chronic myeloid leukemia and high-risk myelodysplastic syndromes, there is significant therapeutic potential in further developing IL1RAP-directed targeting strategies.”

Image by Lance Liotta

A signaling protein may be a “potent” therapeutic target for acute myeloid leukemia (AML), according to a paper published in the Journal of Experimental Medicine.

The protein, interleukin-1 receptor accessory protein (IL1RAP), is often highly expressed on the surface of leukemic stem cells (LSCs) but largely absent from normal hematopoietic stem cells.

Despite this, it wasn’t known whether LSCs require IL1RAP to survive and proliferate and whether inhibiting IL1RAP could be a successful way to treat AML.

Ulrich Steidl, MD, PhD, of Albert Einstein College of Medicine in Bronx, New York, and his colleagues conducted research to find out.

The team found that targeting IL1RAP via RNA interference, genetic deletion, or antibodies induced the death of AML cells, including LSCs, in vitro. These effects were seen in the absence of immune effector cells, indicating that AML cells intrinsically depend on IL1RAP.

In contrast, antibodies targeting IL1RAP had no effect on the growth and survival of normal hematopoietic cells.

In mice, IL1RAP antibody treatment inhibited the proliferation of AML cells without causing any negative side effects.

The researchers also found that IL1RAP’s role in AML is not restricted to the IL-1 receptor pathway.

The team found that IL1RAP enhances the activity of 2 other membrane receptor proteins, FLT3 and c-KIT, which are known to stimulate the proliferation of LSCs when activated by their ligands. IL1RAP antibodies inhibited the ability of these ligands to induce proliferation in AML cells.

“Our findings show that IL1RAP can amplify multiple key pathways in AML, demonstrating a much broader role for this protein in disease pathogenesis than previously appreciated,” Dr Steidl noted.

“Importantly, as IL1RAP is also overexpressed in the stem cells of chronic myeloid leukemia and high-risk myelodysplastic syndromes, there is significant therapeutic potential in further developing IL1RAP-directed targeting strategies.”

Image by Lance Liotta

A signaling protein may be a “potent” therapeutic target for acute myeloid leukemia (AML), according to a paper published in the Journal of Experimental Medicine.

The protein, interleukin-1 receptor accessory protein (IL1RAP), is often highly expressed on the surface of leukemic stem cells (LSCs) but largely absent from normal hematopoietic stem cells.

Despite this, it wasn’t known whether LSCs require IL1RAP to survive and proliferate and whether inhibiting IL1RAP could be a successful way to treat AML.

Ulrich Steidl, MD, PhD, of Albert Einstein College of Medicine in Bronx, New York, and his colleagues conducted research to find out.

The team found that targeting IL1RAP via RNA interference, genetic deletion, or antibodies induced the death of AML cells, including LSCs, in vitro. These effects were seen in the absence of immune effector cells, indicating that AML cells intrinsically depend on IL1RAP.

In contrast, antibodies targeting IL1RAP had no effect on the growth and survival of normal hematopoietic cells.

In mice, IL1RAP antibody treatment inhibited the proliferation of AML cells without causing any negative side effects.

The researchers also found that IL1RAP’s role in AML is not restricted to the IL-1 receptor pathway.

The team found that IL1RAP enhances the activity of 2 other membrane receptor proteins, FLT3 and c-KIT, which are known to stimulate the proliferation of LSCs when activated by their ligands. IL1RAP antibodies inhibited the ability of these ligands to induce proliferation in AML cells.

“Our findings show that IL1RAP can amplify multiple key pathways in AML, demonstrating a much broader role for this protein in disease pathogenesis than previously appreciated,” Dr Steidl noted.

“Importantly, as IL1RAP is also overexpressed in the stem cells of chronic myeloid leukemia and high-risk myelodysplastic syndromes, there is significant therapeutic potential in further developing IL1RAP-directed targeting strategies.”