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Drug receives orphan designation for treatment of MDS
The European Commission has granted orphan designation to asunercept (APG101) for the treatment of myelodysplastic syndromes (MDS).
Asunercept is a fully human fusion protein that consists of the extracellular domain of the CD95 receptor and the Fc domain of an IgG1 antibody.
Asunercept binds to the CD95 ligand and blocks activation of the CD95 receptor.
Excessive stimulation of the CD95 receptor on hematopoietic precursors inhibits erythropoiesis in MDS patients.
As a result, the patients develop transfusion-dependent anemia that is refractory to erythropoiesis-stimulating agents (ESAs).
Treatment with asunercept, by inhibiting the CD95 system, stimulates the production of red blood cells and decreases transfusion dependency.
Asunercept has been evaluated in a phase 1 trial, the results of which were presented at the 2016 ASH Annual Meeting.
The trial enrolled 20 patients with low- to intermediate-risk MDS. All patients had anemia resulting in a high transfusion burden, had hemoglobin levels of less than 10 g/dL, and were refractory to ESAs.
Patients received once-weekly asunercept infusions for 12 weeks. Eight of the 20 patients (40%) experienced a reduction in transfusion frequency for 6 months.
Asunercept was considered generally well tolerated, with no grade 3 or higher treatment-related adverse events reported. The most common treatment-emergent adverse events were peripheral edema (n=6), urinary tract infection (n=4), and oral herpes (n=3).
One patient developed acute myeloid leukemia, and 1 patient died from sepsis due to pre-existing neutropenia.
“We are highly encouraged by the data from our clinical phase 1 trial with asunercept in these patients and are currently preparing to initiate a clinical phase 2 proof-of-concept trial to further evaluate the efficacy of asunercept in MDS,” said Harald Fricke, chief medical officer of Apogenix AG, the company developing asunercept.
About orphan designation
Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.
Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval.
The designation also provides incentives for companies seeking protocol assistance from the European Medicines Agency during the product development phase and direct access to the centralized authorization procedure. 
The European Commission has granted orphan designation to asunercept (APG101) for the treatment of myelodysplastic syndromes (MDS).
Asunercept is a fully human fusion protein that consists of the extracellular domain of the CD95 receptor and the Fc domain of an IgG1 antibody.
Asunercept binds to the CD95 ligand and blocks activation of the CD95 receptor.
Excessive stimulation of the CD95 receptor on hematopoietic precursors inhibits erythropoiesis in MDS patients.
As a result, the patients develop transfusion-dependent anemia that is refractory to erythropoiesis-stimulating agents (ESAs).
Treatment with asunercept, by inhibiting the CD95 system, stimulates the production of red blood cells and decreases transfusion dependency.
Asunercept has been evaluated in a phase 1 trial, the results of which were presented at the 2016 ASH Annual Meeting.
The trial enrolled 20 patients with low- to intermediate-risk MDS. All patients had anemia resulting in a high transfusion burden, had hemoglobin levels of less than 10 g/dL, and were refractory to ESAs.
Patients received once-weekly asunercept infusions for 12 weeks. Eight of the 20 patients (40%) experienced a reduction in transfusion frequency for 6 months.
Asunercept was considered generally well tolerated, with no grade 3 or higher treatment-related adverse events reported. The most common treatment-emergent adverse events were peripheral edema (n=6), urinary tract infection (n=4), and oral herpes (n=3).
One patient developed acute myeloid leukemia, and 1 patient died from sepsis due to pre-existing neutropenia.
“We are highly encouraged by the data from our clinical phase 1 trial with asunercept in these patients and are currently preparing to initiate a clinical phase 2 proof-of-concept trial to further evaluate the efficacy of asunercept in MDS,” said Harald Fricke, chief medical officer of Apogenix AG, the company developing asunercept.
About orphan designation
Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.
Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval.
The designation also provides incentives for companies seeking protocol assistance from the European Medicines Agency during the product development phase and direct access to the centralized authorization procedure.
The European Commission has granted orphan designation to asunercept (APG101) for the treatment of myelodysplastic syndromes (MDS).
Asunercept is a fully human fusion protein that consists of the extracellular domain of the CD95 receptor and the Fc domain of an IgG1 antibody.
Asunercept binds to the CD95 ligand and blocks activation of the CD95 receptor.
Excessive stimulation of the CD95 receptor on hematopoietic precursors inhibits erythropoiesis in MDS patients.
As a result, the patients develop transfusion-dependent anemia that is refractory to erythropoiesis-stimulating agents (ESAs).
Treatment with asunercept, by inhibiting the CD95 system, stimulates the production of red blood cells and decreases transfusion dependency.
Asunercept has been evaluated in a phase 1 trial, the results of which were presented at the 2016 ASH Annual Meeting.
The trial enrolled 20 patients with low- to intermediate-risk MDS. All patients had anemia resulting in a high transfusion burden, had hemoglobin levels of less than 10 g/dL, and were refractory to ESAs.
Patients received once-weekly asunercept infusions for 12 weeks. Eight of the 20 patients (40%) experienced a reduction in transfusion frequency for 6 months.
Asunercept was considered generally well tolerated, with no grade 3 or higher treatment-related adverse events reported. The most common treatment-emergent adverse events were peripheral edema (n=6), urinary tract infection (n=4), and oral herpes (n=3).
One patient developed acute myeloid leukemia, and 1 patient died from sepsis due to pre-existing neutropenia.
“We are highly encouraged by the data from our clinical phase 1 trial with asunercept in these patients and are currently preparing to initiate a clinical phase 2 proof-of-concept trial to further evaluate the efficacy of asunercept in MDS,” said Harald Fricke, chief medical officer of Apogenix AG, the company developing asunercept.
About orphan designation
Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.
Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval.
The designation also provides incentives for companies seeking protocol assistance from the European Medicines Agency during the product development phase and direct access to the centralized authorization procedure.
Mutations impact outcomes in AML, MDS
Researchers say they have identified genetic mutations that can significantly affect treatment outcomes in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS).
The findings come from a clinical trial in which the team examined whether combining vorinostat with azacitidine could improve survival in patients with AML and MDS.
The results showed no additional benefit with the combination, when compared to azacitidine alone.
However, researchers did find that patients had significantly shorter survival times if they had mutations in CDKN2A, IDH1, or TP53.
“This important trial . . . has rapidly answered the important question of whether combining azacitidine with vorinostat improves outcomes for people with AML and MDS and emphasizes the need for further studies with new drug partners for azacitidine,” said Charles Craddock, DPhil, of the Queen Elizabeth Hospital in Birmingham, UK.
“Importantly, the linked molecular studies have shed new light on which people will benefit most from azacitidine. Furthermore, discovering that the CDKN2A gene mutation affects treatment response may be hugely valuable in helping doctors to design new treatment combinations in the future.”
Dr Craddock and his colleagues reported their discoveries in Clinical Cancer Research.
Previous, smaller trials had suggested that adding vorinostat to treatment with azacitidine could improve outcomes for patients with AML and MDS.
To test this idea, Dr Craddock and his colleagues enrolled 259 patients in the current trial. Most of these patients (n=217) had AML—111 were newly diagnosed, 73 had relapsed AML, and 33 had refractory disease.
The remaining 42 patients had MDS—36 were newly diagnosed, 5 had relapsed MDS, and 1 had refractory disease.
Half of patients (n=130) received azacitidine and vorinostat, and the other half received azacitidine alone (n=129).
In both arms, azacitidine was given at 75 mg/m2 on a 5-2-2 schedule, beginning on day 1 of a 28-day cycle for up to 6 cycles. In the combination arm, patients also received vorinostat at 300 mg twice daily for 7 consecutive days, beginning on day 3 of each cycle.
Results
The combination did not significantly improve response rates or survival times.
The overall response rate was 41% in the azacitidine arm and 42% in the combination arm (odds ratio [OR]=1.05, P=0.84).
The rate of compete response (CR)/CR with incomplete count recovery/marrow CR was 22% in the azacitidine arm and 26% in the combination arm (OR=0.82, P=0.49).
The median overall survival (OS) was 9.6 months in the azacitidine arm and 11.0 months in the combination arm (hazard ratio[HR]=1.15, P=0.32).
Impact of mutations
In a multivariable analysis adjusted for all clinical variables, mutations in NPM1 were associated with reduced overall response (OR=8.6, P=0.012).
In another multivariate analysis, mutations in CDKN2A, IDH1, and TP53 were associated with decreased OS. The HRs were 10.0 (P<0.001), 3.6 (P=0.001), and 4.7 (P<0.001), respectively.
The median OS was 4.5 months in patients with CDKN2A mutations and 11.0 months in patients without them.
The median OS was 7.6 months in patients with TP53 mutations and 11.3 months in patients without them.
And the median OS was 5.6 months in patients with IDH1 mutations and 11.1 months in patients without them.
The researchers believe that testing patients newly diagnosed with AML and MDS for CDKN2A, IDH1, and TP53 mutations could help doctors tailor treatment for patients who are less likely to do well.
The team also said the information gleaned from this trial will guide the choice of new drug partners with the potential to increase azacitidine’s clinical activity.
Researchers say they have identified genetic mutations that can significantly affect treatment outcomes in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS).
The findings come from a clinical trial in which the team examined whether combining vorinostat with azacitidine could improve survival in patients with AML and MDS.
The results showed no additional benefit with the combination, when compared to azacitidine alone.
However, researchers did find that patients had significantly shorter survival times if they had mutations in CDKN2A, IDH1, or TP53.
“This important trial . . . has rapidly answered the important question of whether combining azacitidine with vorinostat improves outcomes for people with AML and MDS and emphasizes the need for further studies with new drug partners for azacitidine,” said Charles Craddock, DPhil, of the Queen Elizabeth Hospital in Birmingham, UK.
“Importantly, the linked molecular studies have shed new light on which people will benefit most from azacitidine. Furthermore, discovering that the CDKN2A gene mutation affects treatment response may be hugely valuable in helping doctors to design new treatment combinations in the future.”
Dr Craddock and his colleagues reported their discoveries in Clinical Cancer Research.
Previous, smaller trials had suggested that adding vorinostat to treatment with azacitidine could improve outcomes for patients with AML and MDS.
To test this idea, Dr Craddock and his colleagues enrolled 259 patients in the current trial. Most of these patients (n=217) had AML—111 were newly diagnosed, 73 had relapsed AML, and 33 had refractory disease.
The remaining 42 patients had MDS—36 were newly diagnosed, 5 had relapsed MDS, and 1 had refractory disease.
Half of patients (n=130) received azacitidine and vorinostat, and the other half received azacitidine alone (n=129).
In both arms, azacitidine was given at 75 mg/m2 on a 5-2-2 schedule, beginning on day 1 of a 28-day cycle for up to 6 cycles. In the combination arm, patients also received vorinostat at 300 mg twice daily for 7 consecutive days, beginning on day 3 of each cycle.
Results
The combination did not significantly improve response rates or survival times.
The overall response rate was 41% in the azacitidine arm and 42% in the combination arm (odds ratio [OR]=1.05, P=0.84).
The rate of compete response (CR)/CR with incomplete count recovery/marrow CR was 22% in the azacitidine arm and 26% in the combination arm (OR=0.82, P=0.49).
The median overall survival (OS) was 9.6 months in the azacitidine arm and 11.0 months in the combination arm (hazard ratio[HR]=1.15, P=0.32).
Impact of mutations
In a multivariable analysis adjusted for all clinical variables, mutations in NPM1 were associated with reduced overall response (OR=8.6, P=0.012).
In another multivariate analysis, mutations in CDKN2A, IDH1, and TP53 were associated with decreased OS. The HRs were 10.0 (P<0.001), 3.6 (P=0.001), and 4.7 (P<0.001), respectively.
The median OS was 4.5 months in patients with CDKN2A mutations and 11.0 months in patients without them.
The median OS was 7.6 months in patients with TP53 mutations and 11.3 months in patients without them.
And the median OS was 5.6 months in patients with IDH1 mutations and 11.1 months in patients without them.
The researchers believe that testing patients newly diagnosed with AML and MDS for CDKN2A, IDH1, and TP53 mutations could help doctors tailor treatment for patients who are less likely to do well.
The team also said the information gleaned from this trial will guide the choice of new drug partners with the potential to increase azacitidine’s clinical activity.
Researchers say they have identified genetic mutations that can significantly affect treatment outcomes in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS).
The findings come from a clinical trial in which the team examined whether combining vorinostat with azacitidine could improve survival in patients with AML and MDS.
The results showed no additional benefit with the combination, when compared to azacitidine alone.
However, researchers did find that patients had significantly shorter survival times if they had mutations in CDKN2A, IDH1, or TP53.
“This important trial . . . has rapidly answered the important question of whether combining azacitidine with vorinostat improves outcomes for people with AML and MDS and emphasizes the need for further studies with new drug partners for azacitidine,” said Charles Craddock, DPhil, of the Queen Elizabeth Hospital in Birmingham, UK.
“Importantly, the linked molecular studies have shed new light on which people will benefit most from azacitidine. Furthermore, discovering that the CDKN2A gene mutation affects treatment response may be hugely valuable in helping doctors to design new treatment combinations in the future.”
Dr Craddock and his colleagues reported their discoveries in Clinical Cancer Research.
Previous, smaller trials had suggested that adding vorinostat to treatment with azacitidine could improve outcomes for patients with AML and MDS.
To test this idea, Dr Craddock and his colleagues enrolled 259 patients in the current trial. Most of these patients (n=217) had AML—111 were newly diagnosed, 73 had relapsed AML, and 33 had refractory disease.
The remaining 42 patients had MDS—36 were newly diagnosed, 5 had relapsed MDS, and 1 had refractory disease.
Half of patients (n=130) received azacitidine and vorinostat, and the other half received azacitidine alone (n=129).
In both arms, azacitidine was given at 75 mg/m2 on a 5-2-2 schedule, beginning on day 1 of a 28-day cycle for up to 6 cycles. In the combination arm, patients also received vorinostat at 300 mg twice daily for 7 consecutive days, beginning on day 3 of each cycle.
Results
The combination did not significantly improve response rates or survival times.
The overall response rate was 41% in the azacitidine arm and 42% in the combination arm (odds ratio [OR]=1.05, P=0.84).
The rate of compete response (CR)/CR with incomplete count recovery/marrow CR was 22% in the azacitidine arm and 26% in the combination arm (OR=0.82, P=0.49).
The median overall survival (OS) was 9.6 months in the azacitidine arm and 11.0 months in the combination arm (hazard ratio[HR]=1.15, P=0.32).
Impact of mutations
In a multivariable analysis adjusted for all clinical variables, mutations in NPM1 were associated with reduced overall response (OR=8.6, P=0.012).
In another multivariate analysis, mutations in CDKN2A, IDH1, and TP53 were associated with decreased OS. The HRs were 10.0 (P<0.001), 3.6 (P=0.001), and 4.7 (P<0.001), respectively.
The median OS was 4.5 months in patients with CDKN2A mutations and 11.0 months in patients without them.
The median OS was 7.6 months in patients with TP53 mutations and 11.3 months in patients without them.
And the median OS was 5.6 months in patients with IDH1 mutations and 11.1 months in patients without them.
The researchers believe that testing patients newly diagnosed with AML and MDS for CDKN2A, IDH1, and TP53 mutations could help doctors tailor treatment for patients who are less likely to do well.
The team also said the information gleaned from this trial will guide the choice of new drug partners with the potential to increase azacitidine’s clinical activity.
FDA grants RMAT designation to HSCT adjunct
The US Food and Drug Administration (FDA) has granted Regenerative Medicine Advanced Therapy (RMAT) designation to ATIR101™, which is intended to be used as an adjunct to haploidentical hematopoietic stem cell transplant (HSCT).
ATIR101 is a personalized T-cell immunotherapy—a donor lymphocyte preparation selectively depleted of host-alloreactive T cells through the use of photo-dynamic therapy.
Recipient-reactive T cells from the donor are activated in a unidirectional mixed-lymphocyte reaction. The cells are then treated with TH9402 (a rhodamide-like dye), which is selectively retained in activated T cells.
Subsequent light exposure eliminates the activated recipient-reactive T cells but preserves the other T cells.
The final product is infused after CD34-selected haploidentical HSCT with the goal of preventing infectious complications, graft-versus-host disease (GVHD), and relapse.
About RMAT designation
The RMAT pathway is analogous to the breakthrough therapy designation designed for traditional drug candidates and medical devices. RMAT designation was specifically created by the US Congress in 2016 in the hopes of getting new cell therapies and advanced medicinal products to patients earlier.
Just like breakthrough designation, RMAT designation allows companies developing regenerative medicine therapies to interact with the FDA more frequently in the clinical testing process. In addition, RMAT-designated products may be eligible for priority review and accelerated approval.
A regenerative medicine is eligible for RMAT designation if it is intended to treat, modify, reverse, or cure a serious or life-threatening disease or condition, and if preliminary clinical evidence indicates the treatment has the potential to address unmet medical needs for such a disease or condition.
“To receive the RMAT designation from the FDA is an important milestone for Kiadis Pharma and a recognition by the FDA of the significant potential for ATIR101 to help patients receive safer and more effective bone marrow transplantations,” said Arthur Lahr, CEO of Kiadis Pharma, the company developing ATIR101.
“We are now going to work even closer with the FDA to agree a path to make this cell therapy treatment available for patients in the US as soon as possible. In Europe, ATIR101 was filed for registration in April 2017, and we continue to prepare the company for the potential European launch in 2019.”
ATIR101 trials
Results of a phase 2 trial of ATIR101 were presented at the 42nd Annual Meeting of the European Society of Blood and Marrow Transplantation in 2016.
Patients who received ATIR101 after haploidentical HSCT had significant improvements in transplant-related mortality and overall survival when compared to historical controls who received a T-cell-depleted haploidentical HSCT without ATIR101.
None of the patients who received ATIR101 developed grade 3-4 GVHD, but a few patients did develop grade 2 GVHD.
A phase 3 trial of ATIR101 is now underway. The trial is expected to enroll 200 patients with acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndrome.
The patients will receive a haploidentical HSCT with either a T-cell-depleted graft and adjunctive treatment with ATIR101 or a T-cell-replete graft and post-transplant cyclophosphamide.
The US Food and Drug Administration (FDA) has granted Regenerative Medicine Advanced Therapy (RMAT) designation to ATIR101™, which is intended to be used as an adjunct to haploidentical hematopoietic stem cell transplant (HSCT).
ATIR101 is a personalized T-cell immunotherapy—a donor lymphocyte preparation selectively depleted of host-alloreactive T cells through the use of photo-dynamic therapy.
Recipient-reactive T cells from the donor are activated in a unidirectional mixed-lymphocyte reaction. The cells are then treated with TH9402 (a rhodamide-like dye), which is selectively retained in activated T cells.
Subsequent light exposure eliminates the activated recipient-reactive T cells but preserves the other T cells.
The final product is infused after CD34-selected haploidentical HSCT with the goal of preventing infectious complications, graft-versus-host disease (GVHD), and relapse.
About RMAT designation
The RMAT pathway is analogous to the breakthrough therapy designation designed for traditional drug candidates and medical devices. RMAT designation was specifically created by the US Congress in 2016 in the hopes of getting new cell therapies and advanced medicinal products to patients earlier.
Just like breakthrough designation, RMAT designation allows companies developing regenerative medicine therapies to interact with the FDA more frequently in the clinical testing process. In addition, RMAT-designated products may be eligible for priority review and accelerated approval.
A regenerative medicine is eligible for RMAT designation if it is intended to treat, modify, reverse, or cure a serious or life-threatening disease or condition, and if preliminary clinical evidence indicates the treatment has the potential to address unmet medical needs for such a disease or condition.
“To receive the RMAT designation from the FDA is an important milestone for Kiadis Pharma and a recognition by the FDA of the significant potential for ATIR101 to help patients receive safer and more effective bone marrow transplantations,” said Arthur Lahr, CEO of Kiadis Pharma, the company developing ATIR101.
“We are now going to work even closer with the FDA to agree a path to make this cell therapy treatment available for patients in the US as soon as possible. In Europe, ATIR101 was filed for registration in April 2017, and we continue to prepare the company for the potential European launch in 2019.”
ATIR101 trials
Results of a phase 2 trial of ATIR101 were presented at the 42nd Annual Meeting of the European Society of Blood and Marrow Transplantation in 2016.
Patients who received ATIR101 after haploidentical HSCT had significant improvements in transplant-related mortality and overall survival when compared to historical controls who received a T-cell-depleted haploidentical HSCT without ATIR101.
None of the patients who received ATIR101 developed grade 3-4 GVHD, but a few patients did develop grade 2 GVHD.
A phase 3 trial of ATIR101 is now underway. The trial is expected to enroll 200 patients with acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndrome.
The patients will receive a haploidentical HSCT with either a T-cell-depleted graft and adjunctive treatment with ATIR101 or a T-cell-replete graft and post-transplant cyclophosphamide.
The US Food and Drug Administration (FDA) has granted Regenerative Medicine Advanced Therapy (RMAT) designation to ATIR101™, which is intended to be used as an adjunct to haploidentical hematopoietic stem cell transplant (HSCT).
ATIR101 is a personalized T-cell immunotherapy—a donor lymphocyte preparation selectively depleted of host-alloreactive T cells through the use of photo-dynamic therapy.
Recipient-reactive T cells from the donor are activated in a unidirectional mixed-lymphocyte reaction. The cells are then treated with TH9402 (a rhodamide-like dye), which is selectively retained in activated T cells.
Subsequent light exposure eliminates the activated recipient-reactive T cells but preserves the other T cells.
The final product is infused after CD34-selected haploidentical HSCT with the goal of preventing infectious complications, graft-versus-host disease (GVHD), and relapse.
About RMAT designation
The RMAT pathway is analogous to the breakthrough therapy designation designed for traditional drug candidates and medical devices. RMAT designation was specifically created by the US Congress in 2016 in the hopes of getting new cell therapies and advanced medicinal products to patients earlier.
Just like breakthrough designation, RMAT designation allows companies developing regenerative medicine therapies to interact with the FDA more frequently in the clinical testing process. In addition, RMAT-designated products may be eligible for priority review and accelerated approval.
A regenerative medicine is eligible for RMAT designation if it is intended to treat, modify, reverse, or cure a serious or life-threatening disease or condition, and if preliminary clinical evidence indicates the treatment has the potential to address unmet medical needs for such a disease or condition.
“To receive the RMAT designation from the FDA is an important milestone for Kiadis Pharma and a recognition by the FDA of the significant potential for ATIR101 to help patients receive safer and more effective bone marrow transplantations,” said Arthur Lahr, CEO of Kiadis Pharma, the company developing ATIR101.
“We are now going to work even closer with the FDA to agree a path to make this cell therapy treatment available for patients in the US as soon as possible. In Europe, ATIR101 was filed for registration in April 2017, and we continue to prepare the company for the potential European launch in 2019.”
ATIR101 trials
Results of a phase 2 trial of ATIR101 were presented at the 42nd Annual Meeting of the European Society of Blood and Marrow Transplantation in 2016.
Patients who received ATIR101 after haploidentical HSCT had significant improvements in transplant-related mortality and overall survival when compared to historical controls who received a T-cell-depleted haploidentical HSCT without ATIR101.
None of the patients who received ATIR101 developed grade 3-4 GVHD, but a few patients did develop grade 2 GVHD.
A phase 3 trial of ATIR101 is now underway. The trial is expected to enroll 200 patients with acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndrome.
The patients will receive a haploidentical HSCT with either a T-cell-depleted graft and adjunctive treatment with ATIR101 or a T-cell-replete graft and post-transplant cyclophosphamide.
Antibody shows early promise in AML/MDS trial
MADRID—Interim results of a phase 1 study suggest flotetuzumab, a CD123 and CD3 bispecific antibody, may be a feasible treatment option for relapsed or refractory acute myeloid leukemia (AML) or intermediate/high-risk myelodysplastic syndromes (MDS).
Researchers said flotetuzumab demonstrated acceptable tolerability in the dose-escalation portion of the study, with infusion-related reactions (IRRs) and cytokine release syndrome (CRS) being the most common adverse events (AEs).
In addition, flotetuzumab exhibited anti-leukemic activity in 8 of 14 response-evaluable patients, with 6 patients achieving a response.
Norbert Vey, MD, of Institut Paoli-Calmettes in Marseille, France, presented these results at the ESMO 2017 Congress (abstract 995O*). The study is sponsored by MacroGenics, Inc., the company developing flotetuzumab.
Flotetuzumab (MGD006) recognizes CD123 and CD3. The primary mechanism of flotetuzumab is thought to be its ability to redirect T cells to kill CD123-expressing cells. To achieve this, the molecule combines a portion of an antibody recognizing CD3 (an activating molecule expressed by T cells) with an arm that recognizes CD123 on the target cancer cells.
In this ongoing phase 1 study of flotetuzumab, researchers have enrolled 47 patients with a median age of 64 (range, 29-84). About 89% of these patients had AML (n=42), and the rest (n=5) had MDS.
Twenty-four percent had relapsed AML (n=10), 55% had refractory AML (n=23), and 21% had failed treatment with hypomethylating agents (n=9). One patient had intermediate-1-risk MDS, 2 had intermediate-2-risk, and 2 had high-risk MDS.
Treatment
The study began with single patients receiving flotetuzumab at escalating doses—3 ng/kg/day, 10 ng/kg/day, 30 ng/kg/day, and 100 ng/kg/day.
Then, patients received a range of doses on 2 different schedules for cycle 1. One group received treatment 7 days a week. The other had a 4-days-on/3-days-off schedule.
All patients received a lead-in dose during the first week of cycle 1. They received 30 ng/kg/day for 3 days, then 100 ng/kg/day for 4 days.
For the rest of cycle 1, patients in the 4 days/3 days group received doses of 500 ng/kg, 700 ng/kg, 900 ng/kg, or 1000 ng/kg. Patients in the daily dosing group received doses of 300 ng/kg, 500 ng/kg, 700 ng/kg, 900 ng/kg, or 1000 ng/kg.
For cycle 2 and beyond, all patients were on the 4-days-on/3-days-off schedule.
Safety
The maximum tolerated dose and schedule was 500 ng/kg/day for 7 days.
Dose-limiting toxicities occurring at the 700 ng/kg/day dose included grade 2 IRRs/CRS in 2 patients and grade 3 myalgia in 1 patient. There was 1 drug-related central nervous system AE that led to treatment discontinuation.
IRRs/CRS occurred in 77% of patients, with 13% of patients having grade 3 events and 8.5% of patients discontinuing treatment due to IRRs/CRS.
The researchers said they found ways to decrease the incidence and severity of CRS. One is early intervention with tocilizumab. The other is a 2-step lead-in dose during week 1. So patients first receive 30 ng/kg, then 100 ng/kg, and then their target dose.
Other grade 3 AEs occurring in this trial include febrile neutropenia (11%), anemia (11%), and decreases in platelets (13%), white blood cells (11%), and lymphocytes (13%).
Efficacy
The researchers said they observed encouraging anti-leukemic activity in patients treated at 500 ng/kg/day or greater.
As of the data cut-off, 14 patients treated at this dose were evaluable for response. Eight (57%) patients had anti-leukemic activity, with 6 (43%) of these patients experiencing an objective response.
One patient achieved a complete response (CR), 2 had a CR with incomplete count recovery, and 1 had a molecular CR.
In most responders, anti-leukemic activity was observed after a single cycle of therapy.
MacroGenics is currently enrolling patients in dose-expansion cohorts. The company plans to present updated results from this trial at another scientific conference later this year.
*Slides from this presentation are available on the MacroGenics website at http://ir.macrogenics.com/events.cfm.
MADRID—Interim results of a phase 1 study suggest flotetuzumab, a CD123 and CD3 bispecific antibody, may be a feasible treatment option for relapsed or refractory acute myeloid leukemia (AML) or intermediate/high-risk myelodysplastic syndromes (MDS).
Researchers said flotetuzumab demonstrated acceptable tolerability in the dose-escalation portion of the study, with infusion-related reactions (IRRs) and cytokine release syndrome (CRS) being the most common adverse events (AEs).
In addition, flotetuzumab exhibited anti-leukemic activity in 8 of 14 response-evaluable patients, with 6 patients achieving a response.
Norbert Vey, MD, of Institut Paoli-Calmettes in Marseille, France, presented these results at the ESMO 2017 Congress (abstract 995O*). The study is sponsored by MacroGenics, Inc., the company developing flotetuzumab.
Flotetuzumab (MGD006) recognizes CD123 and CD3. The primary mechanism of flotetuzumab is thought to be its ability to redirect T cells to kill CD123-expressing cells. To achieve this, the molecule combines a portion of an antibody recognizing CD3 (an activating molecule expressed by T cells) with an arm that recognizes CD123 on the target cancer cells.
In this ongoing phase 1 study of flotetuzumab, researchers have enrolled 47 patients with a median age of 64 (range, 29-84). About 89% of these patients had AML (n=42), and the rest (n=5) had MDS.
Twenty-four percent had relapsed AML (n=10), 55% had refractory AML (n=23), and 21% had failed treatment with hypomethylating agents (n=9). One patient had intermediate-1-risk MDS, 2 had intermediate-2-risk, and 2 had high-risk MDS.
Treatment
The study began with single patients receiving flotetuzumab at escalating doses—3 ng/kg/day, 10 ng/kg/day, 30 ng/kg/day, and 100 ng/kg/day.
Then, patients received a range of doses on 2 different schedules for cycle 1. One group received treatment 7 days a week. The other had a 4-days-on/3-days-off schedule.
All patients received a lead-in dose during the first week of cycle 1. They received 30 ng/kg/day for 3 days, then 100 ng/kg/day for 4 days.
For the rest of cycle 1, patients in the 4 days/3 days group received doses of 500 ng/kg, 700 ng/kg, 900 ng/kg, or 1000 ng/kg. Patients in the daily dosing group received doses of 300 ng/kg, 500 ng/kg, 700 ng/kg, 900 ng/kg, or 1000 ng/kg.
For cycle 2 and beyond, all patients were on the 4-days-on/3-days-off schedule.
Safety
The maximum tolerated dose and schedule was 500 ng/kg/day for 7 days.
Dose-limiting toxicities occurring at the 700 ng/kg/day dose included grade 2 IRRs/CRS in 2 patients and grade 3 myalgia in 1 patient. There was 1 drug-related central nervous system AE that led to treatment discontinuation.
IRRs/CRS occurred in 77% of patients, with 13% of patients having grade 3 events and 8.5% of patients discontinuing treatment due to IRRs/CRS.
The researchers said they found ways to decrease the incidence and severity of CRS. One is early intervention with tocilizumab. The other is a 2-step lead-in dose during week 1. So patients first receive 30 ng/kg, then 100 ng/kg, and then their target dose.
Other grade 3 AEs occurring in this trial include febrile neutropenia (11%), anemia (11%), and decreases in platelets (13%), white blood cells (11%), and lymphocytes (13%).
Efficacy
The researchers said they observed encouraging anti-leukemic activity in patients treated at 500 ng/kg/day or greater.
As of the data cut-off, 14 patients treated at this dose were evaluable for response. Eight (57%) patients had anti-leukemic activity, with 6 (43%) of these patients experiencing an objective response.
One patient achieved a complete response (CR), 2 had a CR with incomplete count recovery, and 1 had a molecular CR.
In most responders, anti-leukemic activity was observed after a single cycle of therapy.
MacroGenics is currently enrolling patients in dose-expansion cohorts. The company plans to present updated results from this trial at another scientific conference later this year.
*Slides from this presentation are available on the MacroGenics website at http://ir.macrogenics.com/events.cfm.
MADRID—Interim results of a phase 1 study suggest flotetuzumab, a CD123 and CD3 bispecific antibody, may be a feasible treatment option for relapsed or refractory acute myeloid leukemia (AML) or intermediate/high-risk myelodysplastic syndromes (MDS).
Researchers said flotetuzumab demonstrated acceptable tolerability in the dose-escalation portion of the study, with infusion-related reactions (IRRs) and cytokine release syndrome (CRS) being the most common adverse events (AEs).
In addition, flotetuzumab exhibited anti-leukemic activity in 8 of 14 response-evaluable patients, with 6 patients achieving a response.
Norbert Vey, MD, of Institut Paoli-Calmettes in Marseille, France, presented these results at the ESMO 2017 Congress (abstract 995O*). The study is sponsored by MacroGenics, Inc., the company developing flotetuzumab.
Flotetuzumab (MGD006) recognizes CD123 and CD3. The primary mechanism of flotetuzumab is thought to be its ability to redirect T cells to kill CD123-expressing cells. To achieve this, the molecule combines a portion of an antibody recognizing CD3 (an activating molecule expressed by T cells) with an arm that recognizes CD123 on the target cancer cells.
In this ongoing phase 1 study of flotetuzumab, researchers have enrolled 47 patients with a median age of 64 (range, 29-84). About 89% of these patients had AML (n=42), and the rest (n=5) had MDS.
Twenty-four percent had relapsed AML (n=10), 55% had refractory AML (n=23), and 21% had failed treatment with hypomethylating agents (n=9). One patient had intermediate-1-risk MDS, 2 had intermediate-2-risk, and 2 had high-risk MDS.
Treatment
The study began with single patients receiving flotetuzumab at escalating doses—3 ng/kg/day, 10 ng/kg/day, 30 ng/kg/day, and 100 ng/kg/day.
Then, patients received a range of doses on 2 different schedules for cycle 1. One group received treatment 7 days a week. The other had a 4-days-on/3-days-off schedule.
All patients received a lead-in dose during the first week of cycle 1. They received 30 ng/kg/day for 3 days, then 100 ng/kg/day for 4 days.
For the rest of cycle 1, patients in the 4 days/3 days group received doses of 500 ng/kg, 700 ng/kg, 900 ng/kg, or 1000 ng/kg. Patients in the daily dosing group received doses of 300 ng/kg, 500 ng/kg, 700 ng/kg, 900 ng/kg, or 1000 ng/kg.
For cycle 2 and beyond, all patients were on the 4-days-on/3-days-off schedule.
Safety
The maximum tolerated dose and schedule was 500 ng/kg/day for 7 days.
Dose-limiting toxicities occurring at the 700 ng/kg/day dose included grade 2 IRRs/CRS in 2 patients and grade 3 myalgia in 1 patient. There was 1 drug-related central nervous system AE that led to treatment discontinuation.
IRRs/CRS occurred in 77% of patients, with 13% of patients having grade 3 events and 8.5% of patients discontinuing treatment due to IRRs/CRS.
The researchers said they found ways to decrease the incidence and severity of CRS. One is early intervention with tocilizumab. The other is a 2-step lead-in dose during week 1. So patients first receive 30 ng/kg, then 100 ng/kg, and then their target dose.
Other grade 3 AEs occurring in this trial include febrile neutropenia (11%), anemia (11%), and decreases in platelets (13%), white blood cells (11%), and lymphocytes (13%).
Efficacy
The researchers said they observed encouraging anti-leukemic activity in patients treated at 500 ng/kg/day or greater.
As of the data cut-off, 14 patients treated at this dose were evaluable for response. Eight (57%) patients had anti-leukemic activity, with 6 (43%) of these patients experiencing an objective response.
One patient achieved a complete response (CR), 2 had a CR with incomplete count recovery, and 1 had a molecular CR.
In most responders, anti-leukemic activity was observed after a single cycle of therapy.
MacroGenics is currently enrolling patients in dose-expansion cohorts. The company plans to present updated results from this trial at another scientific conference later this year.
*Slides from this presentation are available on the MacroGenics website at http://ir.macrogenics.com/events.cfm.
CHMP recommends approval of generic imatinib
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended granting marketing authorization for Imatinib Teva B.V., a generic of Glivec.
The recommendation is that Imatinib Teva B.V. be approved to treat chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), hypereosinophilic syndrome (HES), chronic eosinophilic leukemia (CEL), myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPNs), gastrointestinal stromal tumors (GIST), and dermatofibrosarcoma protuberans (DFSP).
The European Commission typically adheres to the CHMP’s recommendations and delivers its final decision within 67 days of the CHMP’s recommendation.
The European Commission’s decision will be applicable to the entire European Economic Area—all member states of the European Union plus Iceland, Liechtenstein, and Norway.
If approved, Imatinib Teva B.V. will be available as capsules and film-coated tablets (100 mg and 400 mg). And it will be authorized:
- As monotherapy for pediatric patients with newly diagnosed, Philadelphia-chromosome-positive (Ph+) CML for whom bone marrow transplant is not considered the first line of treatment.
- As monotherapy for pediatric patients with Ph+ CML in chronic phase after failure of interferon-alpha therapy or in accelerated phase or blast crisis.
- As monotherapy for adults with Ph+ CML in blast crisis.
- Integrated with chemotherapy to treat adult and pediatric patients with newly diagnosed, Ph+ ALL.
- As monotherapy for adults with relapsed or refractory Ph+ ALL.
- As monotherapy for adults with MDS/MPNs associated with platelet-derived growth factor receptor gene re-arrangements.
- As monotherapy for adults with advanced HES and/or CEL with FIP1L1-PDGFRα rearrangement.
- As monotherapy for adults with Kit- (CD117-) positive, unresectable and/or metastatic malignant GISTs.
- For the adjuvant treatment of adults who are at significant risk of relapse following resection of Kit-positive GIST. Patients who have a low or very low risk of recurrence should not receive adjuvant treatment.
- As monotherapy for adults with unresectable DFSP and adults with recurrent and/or metastatic DFSP who are not eligible for surgery.
The CHMP said studies have demonstrated the satisfactory quality of Imatinib Teva B.V. and its bioequivalence to the reference product, Glivec.
In adult and pediatric patients, the effectiveness of imatinib is based on:
- Overall hematologic and cytogenetic response rates and progression-free survival in CML
- Hematologic and cytogenetic response rates in Ph+ ALL and MDS/MPNs
- Hematologic response rates in HES/CEL
- Objective response rates in adults with unresectable and/or metastatic GIST and DFSP
- Recurrence-free survival in adjuvant GIST.
The experience with imatinib in patients with MDS/MPNs associated with PDGFR gene re-arrangements is very limited. There are no controlled trials demonstrating a clinical benefit or increased survival for these diseases.
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended granting marketing authorization for Imatinib Teva B.V., a generic of Glivec.
The recommendation is that Imatinib Teva B.V. be approved to treat chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), hypereosinophilic syndrome (HES), chronic eosinophilic leukemia (CEL), myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPNs), gastrointestinal stromal tumors (GIST), and dermatofibrosarcoma protuberans (DFSP).
The European Commission typically adheres to the CHMP’s recommendations and delivers its final decision within 67 days of the CHMP’s recommendation.
The European Commission’s decision will be applicable to the entire European Economic Area—all member states of the European Union plus Iceland, Liechtenstein, and Norway.
If approved, Imatinib Teva B.V. will be available as capsules and film-coated tablets (100 mg and 400 mg). And it will be authorized:
- As monotherapy for pediatric patients with newly diagnosed, Philadelphia-chromosome-positive (Ph+) CML for whom bone marrow transplant is not considered the first line of treatment.
- As monotherapy for pediatric patients with Ph+ CML in chronic phase after failure of interferon-alpha therapy or in accelerated phase or blast crisis.
- As monotherapy for adults with Ph+ CML in blast crisis.
- Integrated with chemotherapy to treat adult and pediatric patients with newly diagnosed, Ph+ ALL.
- As monotherapy for adults with relapsed or refractory Ph+ ALL.
- As monotherapy for adults with MDS/MPNs associated with platelet-derived growth factor receptor gene re-arrangements.
- As monotherapy for adults with advanced HES and/or CEL with FIP1L1-PDGFRα rearrangement.
- As monotherapy for adults with Kit- (CD117-) positive, unresectable and/or metastatic malignant GISTs.
- For the adjuvant treatment of adults who are at significant risk of relapse following resection of Kit-positive GIST. Patients who have a low or very low risk of recurrence should not receive adjuvant treatment.
- As monotherapy for adults with unresectable DFSP and adults with recurrent and/or metastatic DFSP who are not eligible for surgery.
The CHMP said studies have demonstrated the satisfactory quality of Imatinib Teva B.V. and its bioequivalence to the reference product, Glivec.
In adult and pediatric patients, the effectiveness of imatinib is based on:
- Overall hematologic and cytogenetic response rates and progression-free survival in CML
- Hematologic and cytogenetic response rates in Ph+ ALL and MDS/MPNs
- Hematologic response rates in HES/CEL
- Objective response rates in adults with unresectable and/or metastatic GIST and DFSP
- Recurrence-free survival in adjuvant GIST.
The experience with imatinib in patients with MDS/MPNs associated with PDGFR gene re-arrangements is very limited. There are no controlled trials demonstrating a clinical benefit or increased survival for these diseases.
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended granting marketing authorization for Imatinib Teva B.V., a generic of Glivec.
The recommendation is that Imatinib Teva B.V. be approved to treat chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), hypereosinophilic syndrome (HES), chronic eosinophilic leukemia (CEL), myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPNs), gastrointestinal stromal tumors (GIST), and dermatofibrosarcoma protuberans (DFSP).
The European Commission typically adheres to the CHMP’s recommendations and delivers its final decision within 67 days of the CHMP’s recommendation.
The European Commission’s decision will be applicable to the entire European Economic Area—all member states of the European Union plus Iceland, Liechtenstein, and Norway.
If approved, Imatinib Teva B.V. will be available as capsules and film-coated tablets (100 mg and 400 mg). And it will be authorized:
- As monotherapy for pediatric patients with newly diagnosed, Philadelphia-chromosome-positive (Ph+) CML for whom bone marrow transplant is not considered the first line of treatment.
- As monotherapy for pediatric patients with Ph+ CML in chronic phase after failure of interferon-alpha therapy or in accelerated phase or blast crisis.
- As monotherapy for adults with Ph+ CML in blast crisis.
- Integrated with chemotherapy to treat adult and pediatric patients with newly diagnosed, Ph+ ALL.
- As monotherapy for adults with relapsed or refractory Ph+ ALL.
- As monotherapy for adults with MDS/MPNs associated with platelet-derived growth factor receptor gene re-arrangements.
- As monotherapy for adults with advanced HES and/or CEL with FIP1L1-PDGFRα rearrangement.
- As monotherapy for adults with Kit- (CD117-) positive, unresectable and/or metastatic malignant GISTs.
- For the adjuvant treatment of adults who are at significant risk of relapse following resection of Kit-positive GIST. Patients who have a low or very low risk of recurrence should not receive adjuvant treatment.
- As monotherapy for adults with unresectable DFSP and adults with recurrent and/or metastatic DFSP who are not eligible for surgery.
The CHMP said studies have demonstrated the satisfactory quality of Imatinib Teva B.V. and its bioequivalence to the reference product, Glivec.
In adult and pediatric patients, the effectiveness of imatinib is based on:
- Overall hematologic and cytogenetic response rates and progression-free survival in CML
- Hematologic and cytogenetic response rates in Ph+ ALL and MDS/MPNs
- Hematologic response rates in HES/CEL
- Objective response rates in adults with unresectable and/or metastatic GIST and DFSP
- Recurrence-free survival in adjuvant GIST.
The experience with imatinib in patients with MDS/MPNs associated with PDGFR gene re-arrangements is very limited. There are no controlled trials demonstrating a clinical benefit or increased survival for these diseases.
VSTs can treat 5 different viral infections after HSCT
New research suggests virus-specific T cells (VSTs) can protect patients from severe viral infections that sometimes occur after hematopoietic stem cell transplant (HSCT).
The VSTs proved effective against 5 different viruses—Epstein-Barr virus (EBV), adenovirus (AdV), cytomegalovirus (CMV), BK virus (BKV), and human herpesvirus 6 (HHV-6).
Ifigeneia Tzannou, MD, of Baylor College of Medicine in Houston, Texas, and her colleagues reported these findings in the Journal of Clinical Oncology.
“In this study, we continued our previous work . . . in which we showed that patients who had developed an Epstein-Barr virus infection after a transplant . . . could be helped by receiving immune cells specialized in eliminating that particular virus,” Dr Tzannou said. “Then, we and others successfully targeted other viruses—namely, adenoviruses and cytomegalovirus.”
“The novel contribution of this study is that we have targeted additional viruses, the BK virus and the HHV-6 virus, which had not been targeted this way before,” added study author Bilal Omer, MD, of Baylor College of Medicine.
“This is important because the BK virus does not have an effective treatment, and the complications are significant, including severe pain and bleeding. These patients are in the hospital for weeks, months sometimes, and, now, we have a treatment option.”
The researchers tested their VSTs in a phase 2 trial of 38 HSCT recipients with at least 1 of the aforementioned viruses.
“[To prepare the VSTs,] we take blood from healthy donors who have already been exposed to these viruses and who we have confirmed have immune cells that can fight the infections,” Dr Tzannou said.
“We isolate the cells and let them multiply in culture. The final product is a mixture of cells that, together, can target all 5 viruses. We prepared 59 sets of virus-specific cells from different donors following this procedure.”
“Our strategy is to prepare a number of sets of virus-specific cells ahead of time and store them in a freezer, ready to use when a patient needs them,” Dr Omer noted. “To match patient and donor, we use elaborate matching algorithms.”
Patients
The trial included 38 patients who had undergone HSCT to treat acute myeloid leukemia/myelodysplastic syndromes (n=20), acute lymphoblastic leukemia (n=9), lymphoma/myeloma (n=3), or nonmalignant disorders (n=6).
These 38 patients had a total of 45 infections—CMV (n=17), EBV (n=2), AdV (n=7), BKV (n=16), and HHV-6 (n=3).
Response
The researchers monitored virus levels and other clinical responses in the 37 evaluable patients.
Six weeks after the first VST infusion, the overall response rate was 91.9%.
Seventeen patients received VSTs for persistent CMV. Sixteen of these patients (94.1%) responded, 6 with complete responses (CRs) and 10 with partial responses (PRs).
Two patients received VSTs for EBV, and both achieved a virologic CR.
Seven patients received VSTs for persistent AdV. The response rate was 71.4%. Four patients achieved a CR, 1 had a PR, and 2 patients did not respond.
Three patients received VSTs to treat HHV-6 reactivations. The response rate was 67%. Two patients had a PR, and 1 was not evaluable.
Sixteen patients received VSTs for BKV-associated hemorrhagic cystitis (n= 14) or BKV-associated nephritis (n=2).
All 16 patients responded. One had a clinical and virologic CR. Six had a clinical CR but a virologic PR. Seven had a virologic and clinical PR. And 2 patients had only a virologic PR.
A total of 15 patients received a second VST infusion—1 due to lack of response, 7 who had a PR, and 7 due to recurrence. Ten of these patients responded to the second infusion—1 with a CR and 9 with a PR.
Four patients received a third infusion of VSTs. Two achieved a CR, 1 had a PR, and 1 did not respond.
Toxicity
One patient developed an isolated fever within 24 hours of VST infusion, but the researchers did not observe any other immediate toxicities.
One of the patients with BKV-associated hemorrhagic cystitis experienced transient hydronephrosis and a decrease in renal function associated with a concomitant bacterial urinary tract infection.
Nineteen patients had prior grade 2 to 4 graft-versus-host disease (GVHD)—15 with grade 2 and 4 with grade 3. All GVHD was quiescent at the time of VST infusion.
One patient developed recurrent grade 3 gastrointestinal GVHD after VST infusion and rapid corticosteroid taper. Five patients developed recurrent (n=3) or de novo (n=2) grade 1 to 2 skin GVHD, which resolved with topical treatment (n=4) and reinitiation of corticosteroid treatment (n=1).
Two patients had a flare of upper-gastrointestinal GVHD, which resolved after a brief corticosteroid course.
“We didn’t have any significant toxicities,” Dr Tzannou said. “Taken together, the results of this trial suggest that it is reasonable to consider this treatment as an early option for these patients. We hope that the results of a future multicenter, phase 3 clinical trial will help raise awareness in both physicians and patients that this treatment, which is safe and effective, is available.”
New research suggests virus-specific T cells (VSTs) can protect patients from severe viral infections that sometimes occur after hematopoietic stem cell transplant (HSCT).
The VSTs proved effective against 5 different viruses—Epstein-Barr virus (EBV), adenovirus (AdV), cytomegalovirus (CMV), BK virus (BKV), and human herpesvirus 6 (HHV-6).
Ifigeneia Tzannou, MD, of Baylor College of Medicine in Houston, Texas, and her colleagues reported these findings in the Journal of Clinical Oncology.
“In this study, we continued our previous work . . . in which we showed that patients who had developed an Epstein-Barr virus infection after a transplant . . . could be helped by receiving immune cells specialized in eliminating that particular virus,” Dr Tzannou said. “Then, we and others successfully targeted other viruses—namely, adenoviruses and cytomegalovirus.”
“The novel contribution of this study is that we have targeted additional viruses, the BK virus and the HHV-6 virus, which had not been targeted this way before,” added study author Bilal Omer, MD, of Baylor College of Medicine.
“This is important because the BK virus does not have an effective treatment, and the complications are significant, including severe pain and bleeding. These patients are in the hospital for weeks, months sometimes, and, now, we have a treatment option.”
The researchers tested their VSTs in a phase 2 trial of 38 HSCT recipients with at least 1 of the aforementioned viruses.
“[To prepare the VSTs,] we take blood from healthy donors who have already been exposed to these viruses and who we have confirmed have immune cells that can fight the infections,” Dr Tzannou said.
“We isolate the cells and let them multiply in culture. The final product is a mixture of cells that, together, can target all 5 viruses. We prepared 59 sets of virus-specific cells from different donors following this procedure.”
“Our strategy is to prepare a number of sets of virus-specific cells ahead of time and store them in a freezer, ready to use when a patient needs them,” Dr Omer noted. “To match patient and donor, we use elaborate matching algorithms.”
Patients
The trial included 38 patients who had undergone HSCT to treat acute myeloid leukemia/myelodysplastic syndromes (n=20), acute lymphoblastic leukemia (n=9), lymphoma/myeloma (n=3), or nonmalignant disorders (n=6).
These 38 patients had a total of 45 infections—CMV (n=17), EBV (n=2), AdV (n=7), BKV (n=16), and HHV-6 (n=3).
Response
The researchers monitored virus levels and other clinical responses in the 37 evaluable patients.
Six weeks after the first VST infusion, the overall response rate was 91.9%.
Seventeen patients received VSTs for persistent CMV. Sixteen of these patients (94.1%) responded, 6 with complete responses (CRs) and 10 with partial responses (PRs).
Two patients received VSTs for EBV, and both achieved a virologic CR.
Seven patients received VSTs for persistent AdV. The response rate was 71.4%. Four patients achieved a CR, 1 had a PR, and 2 patients did not respond.
Three patients received VSTs to treat HHV-6 reactivations. The response rate was 67%. Two patients had a PR, and 1 was not evaluable.
Sixteen patients received VSTs for BKV-associated hemorrhagic cystitis (n= 14) or BKV-associated nephritis (n=2).
All 16 patients responded. One had a clinical and virologic CR. Six had a clinical CR but a virologic PR. Seven had a virologic and clinical PR. And 2 patients had only a virologic PR.
A total of 15 patients received a second VST infusion—1 due to lack of response, 7 who had a PR, and 7 due to recurrence. Ten of these patients responded to the second infusion—1 with a CR and 9 with a PR.
Four patients received a third infusion of VSTs. Two achieved a CR, 1 had a PR, and 1 did not respond.
Toxicity
One patient developed an isolated fever within 24 hours of VST infusion, but the researchers did not observe any other immediate toxicities.
One of the patients with BKV-associated hemorrhagic cystitis experienced transient hydronephrosis and a decrease in renal function associated with a concomitant bacterial urinary tract infection.
Nineteen patients had prior grade 2 to 4 graft-versus-host disease (GVHD)—15 with grade 2 and 4 with grade 3. All GVHD was quiescent at the time of VST infusion.
One patient developed recurrent grade 3 gastrointestinal GVHD after VST infusion and rapid corticosteroid taper. Five patients developed recurrent (n=3) or de novo (n=2) grade 1 to 2 skin GVHD, which resolved with topical treatment (n=4) and reinitiation of corticosteroid treatment (n=1).
Two patients had a flare of upper-gastrointestinal GVHD, which resolved after a brief corticosteroid course.
“We didn’t have any significant toxicities,” Dr Tzannou said. “Taken together, the results of this trial suggest that it is reasonable to consider this treatment as an early option for these patients. We hope that the results of a future multicenter, phase 3 clinical trial will help raise awareness in both physicians and patients that this treatment, which is safe and effective, is available.”
New research suggests virus-specific T cells (VSTs) can protect patients from severe viral infections that sometimes occur after hematopoietic stem cell transplant (HSCT).
The VSTs proved effective against 5 different viruses—Epstein-Barr virus (EBV), adenovirus (AdV), cytomegalovirus (CMV), BK virus (BKV), and human herpesvirus 6 (HHV-6).
Ifigeneia Tzannou, MD, of Baylor College of Medicine in Houston, Texas, and her colleagues reported these findings in the Journal of Clinical Oncology.
“In this study, we continued our previous work . . . in which we showed that patients who had developed an Epstein-Barr virus infection after a transplant . . . could be helped by receiving immune cells specialized in eliminating that particular virus,” Dr Tzannou said. “Then, we and others successfully targeted other viruses—namely, adenoviruses and cytomegalovirus.”
“The novel contribution of this study is that we have targeted additional viruses, the BK virus and the HHV-6 virus, which had not been targeted this way before,” added study author Bilal Omer, MD, of Baylor College of Medicine.
“This is important because the BK virus does not have an effective treatment, and the complications are significant, including severe pain and bleeding. These patients are in the hospital for weeks, months sometimes, and, now, we have a treatment option.”
The researchers tested their VSTs in a phase 2 trial of 38 HSCT recipients with at least 1 of the aforementioned viruses.
“[To prepare the VSTs,] we take blood from healthy donors who have already been exposed to these viruses and who we have confirmed have immune cells that can fight the infections,” Dr Tzannou said.
“We isolate the cells and let them multiply in culture. The final product is a mixture of cells that, together, can target all 5 viruses. We prepared 59 sets of virus-specific cells from different donors following this procedure.”
“Our strategy is to prepare a number of sets of virus-specific cells ahead of time and store them in a freezer, ready to use when a patient needs them,” Dr Omer noted. “To match patient and donor, we use elaborate matching algorithms.”
Patients
The trial included 38 patients who had undergone HSCT to treat acute myeloid leukemia/myelodysplastic syndromes (n=20), acute lymphoblastic leukemia (n=9), lymphoma/myeloma (n=3), or nonmalignant disorders (n=6).
These 38 patients had a total of 45 infections—CMV (n=17), EBV (n=2), AdV (n=7), BKV (n=16), and HHV-6 (n=3).
Response
The researchers monitored virus levels and other clinical responses in the 37 evaluable patients.
Six weeks after the first VST infusion, the overall response rate was 91.9%.
Seventeen patients received VSTs for persistent CMV. Sixteen of these patients (94.1%) responded, 6 with complete responses (CRs) and 10 with partial responses (PRs).
Two patients received VSTs for EBV, and both achieved a virologic CR.
Seven patients received VSTs for persistent AdV. The response rate was 71.4%. Four patients achieved a CR, 1 had a PR, and 2 patients did not respond.
Three patients received VSTs to treat HHV-6 reactivations. The response rate was 67%. Two patients had a PR, and 1 was not evaluable.
Sixteen patients received VSTs for BKV-associated hemorrhagic cystitis (n= 14) or BKV-associated nephritis (n=2).
All 16 patients responded. One had a clinical and virologic CR. Six had a clinical CR but a virologic PR. Seven had a virologic and clinical PR. And 2 patients had only a virologic PR.
A total of 15 patients received a second VST infusion—1 due to lack of response, 7 who had a PR, and 7 due to recurrence. Ten of these patients responded to the second infusion—1 with a CR and 9 with a PR.
Four patients received a third infusion of VSTs. Two achieved a CR, 1 had a PR, and 1 did not respond.
Toxicity
One patient developed an isolated fever within 24 hours of VST infusion, but the researchers did not observe any other immediate toxicities.
One of the patients with BKV-associated hemorrhagic cystitis experienced transient hydronephrosis and a decrease in renal function associated with a concomitant bacterial urinary tract infection.
Nineteen patients had prior grade 2 to 4 graft-versus-host disease (GVHD)—15 with grade 2 and 4 with grade 3. All GVHD was quiescent at the time of VST infusion.
One patient developed recurrent grade 3 gastrointestinal GVHD after VST infusion and rapid corticosteroid taper. Five patients developed recurrent (n=3) or de novo (n=2) grade 1 to 2 skin GVHD, which resolved with topical treatment (n=4) and reinitiation of corticosteroid treatment (n=1).
Two patients had a flare of upper-gastrointestinal GVHD, which resolved after a brief corticosteroid course.
“We didn’t have any significant toxicities,” Dr Tzannou said. “Taken together, the results of this trial suggest that it is reasonable to consider this treatment as an early option for these patients. We hope that the results of a future multicenter, phase 3 clinical trial will help raise awareness in both physicians and patients that this treatment, which is safe and effective, is available.”
Vemurafenib granted sNDA, priority review for Erdheim-Chester disease
Vemurafenib (Zelboraf) has been granted a supplemental new drug application and priority review by the Food and Drug Administration for the treatment of Erdheim-Chester disease with BRAF V600 mutation, according to a press release issued by Genentech.
The FDA is expected to make a decision on the indication by Dec. 7, 2017. Vemurafenib is approved for the treatment of unresectable or metastatic melanoma with BRAF V600E mutation.
The supportive data for the application came from VE-BASKET, a phase 2, nonrandomized study investigating the use of vemurafenib for people with various BRAF V600 mutation–positive cancers and other diseases. Final results for the 22 people with Erdheim-Chester disease showed a best overall response rate of 54.5% by RECIST v1.1 criteria.
The median duration of response, progression-free survival, and overall survival were not reached at a median follow-up time of 26.6 months. The most common grade 3 or higher adverse events were new skin cancers, high blood pressure, rash, and joint pain. Initial study results were published in the New England Journal of Medicine in August 2015.
Based on available published data, there are fewer than 500 cases of Erdheim-Chester disease in the United States. More than half of affected people have BRAF V600 mutation–positive disease, and there are no approved treatments, according to the release.
Vemurafenib (Zelboraf) has been granted a supplemental new drug application and priority review by the Food and Drug Administration for the treatment of Erdheim-Chester disease with BRAF V600 mutation, according to a press release issued by Genentech.
The FDA is expected to make a decision on the indication by Dec. 7, 2017. Vemurafenib is approved for the treatment of unresectable or metastatic melanoma with BRAF V600E mutation.
The supportive data for the application came from VE-BASKET, a phase 2, nonrandomized study investigating the use of vemurafenib for people with various BRAF V600 mutation–positive cancers and other diseases. Final results for the 22 people with Erdheim-Chester disease showed a best overall response rate of 54.5% by RECIST v1.1 criteria.
The median duration of response, progression-free survival, and overall survival were not reached at a median follow-up time of 26.6 months. The most common grade 3 or higher adverse events were new skin cancers, high blood pressure, rash, and joint pain. Initial study results were published in the New England Journal of Medicine in August 2015.
Based on available published data, there are fewer than 500 cases of Erdheim-Chester disease in the United States. More than half of affected people have BRAF V600 mutation–positive disease, and there are no approved treatments, according to the release.
Vemurafenib (Zelboraf) has been granted a supplemental new drug application and priority review by the Food and Drug Administration for the treatment of Erdheim-Chester disease with BRAF V600 mutation, according to a press release issued by Genentech.
The FDA is expected to make a decision on the indication by Dec. 7, 2017. Vemurafenib is approved for the treatment of unresectable or metastatic melanoma with BRAF V600E mutation.
The supportive data for the application came from VE-BASKET, a phase 2, nonrandomized study investigating the use of vemurafenib for people with various BRAF V600 mutation–positive cancers and other diseases. Final results for the 22 people with Erdheim-Chester disease showed a best overall response rate of 54.5% by RECIST v1.1 criteria.
The median duration of response, progression-free survival, and overall survival were not reached at a median follow-up time of 26.6 months. The most common grade 3 or higher adverse events were new skin cancers, high blood pressure, rash, and joint pain. Initial study results were published in the New England Journal of Medicine in August 2015.
Based on available published data, there are fewer than 500 cases of Erdheim-Chester disease in the United States. More than half of affected people have BRAF V600 mutation–positive disease, and there are no approved treatments, according to the release.
Predicting response to treatment in AML, MDS
Researchers say they have determined which patients will respond to treatment with SY-1425, a retinoic acid receptor alpha (RARα) agonist.
The team discovered a subset of patients with acute myeloid leukemia (AML) who had a super-enhancer associated with the RARA gene, which is predictive of response to SY-1425.
The researchers also identified a subset of patients with myelodysplastic syndromes (MDS) who had high expression of the RARA gene.
And experiments showed that RARA-high MDS had a similar response to SY-1425 as that seen in AML driven by the RARA super-enhancer.
Ravindra Majeti MD, PhD, of Stanford University School of Medicine in California, and colleagues reported these findings in Cancer Discovery. Employees of Syros Pharmaceuticals, the company developing SY-1425, were also involved in this research.
In collaboration with the Majeti lab, Syros used its gene control platform to analyze 66 AML patients’ tumor samples. In this way, the researchers identified 6 distinct patient subsets based on super-enhancer profiles, including 1 enriched for a super-enhancer associated with the RARA gene.
The team found that super-enhancer profiles were strongly associated with survival outcomes, often independent of known genetic mutations in AML.
The RARA super-enhancer was associated with high expression of the RARA gene, which codes for a transcription factor targeted by SY-1425.
The RARA super-enhancer was predictive of response to SY-1425. In AML cells with high RARA expression, SY-1425 reduced proliferation and promoted differentiation.
Moreover, SY-1425 decreased tumor burden and prolonged survival in patient-derived xenograft models of AML with high RARA expression. However, there was no effect on AML cells or models with low RARA expression.
The researchers said SY-1425 induced profound transcriptional changes promoting cell differentiation in AML cells with high RARA expression, but the drug produced little to no transcriptional changes in AML cells with low RARA expression.
DHRS3 was the most strongly and rapidly induced gene in response to treatment with SY-1425. This led to the identification of DHRS3 induction as an early indicator of whether SY-1425 is affecting the targeted biology in defined subsets of AML and MDS patients. It is therefore used as a pharmacodynamic marker in the ongoing phase 2 trial of SY-1425.
In this trial, researchers are assessing the safety and efficacy of SY-1425 as a single agent in 4 AML and MDS patient populations, as well as testing SY-1425 in combination with azacitidine in newly diagnosed AML patients who are not suitable candidates for standard chemotherapy.
Researchers say they have determined which patients will respond to treatment with SY-1425, a retinoic acid receptor alpha (RARα) agonist.
The team discovered a subset of patients with acute myeloid leukemia (AML) who had a super-enhancer associated with the RARA gene, which is predictive of response to SY-1425.
The researchers also identified a subset of patients with myelodysplastic syndromes (MDS) who had high expression of the RARA gene.
And experiments showed that RARA-high MDS had a similar response to SY-1425 as that seen in AML driven by the RARA super-enhancer.
Ravindra Majeti MD, PhD, of Stanford University School of Medicine in California, and colleagues reported these findings in Cancer Discovery. Employees of Syros Pharmaceuticals, the company developing SY-1425, were also involved in this research.
In collaboration with the Majeti lab, Syros used its gene control platform to analyze 66 AML patients’ tumor samples. In this way, the researchers identified 6 distinct patient subsets based on super-enhancer profiles, including 1 enriched for a super-enhancer associated with the RARA gene.
The team found that super-enhancer profiles were strongly associated with survival outcomes, often independent of known genetic mutations in AML.
The RARA super-enhancer was associated with high expression of the RARA gene, which codes for a transcription factor targeted by SY-1425.
The RARA super-enhancer was predictive of response to SY-1425. In AML cells with high RARA expression, SY-1425 reduced proliferation and promoted differentiation.
Moreover, SY-1425 decreased tumor burden and prolonged survival in patient-derived xenograft models of AML with high RARA expression. However, there was no effect on AML cells or models with low RARA expression.
The researchers said SY-1425 induced profound transcriptional changes promoting cell differentiation in AML cells with high RARA expression, but the drug produced little to no transcriptional changes in AML cells with low RARA expression.
DHRS3 was the most strongly and rapidly induced gene in response to treatment with SY-1425. This led to the identification of DHRS3 induction as an early indicator of whether SY-1425 is affecting the targeted biology in defined subsets of AML and MDS patients. It is therefore used as a pharmacodynamic marker in the ongoing phase 2 trial of SY-1425.
In this trial, researchers are assessing the safety and efficacy of SY-1425 as a single agent in 4 AML and MDS patient populations, as well as testing SY-1425 in combination with azacitidine in newly diagnosed AML patients who are not suitable candidates for standard chemotherapy.
Researchers say they have determined which patients will respond to treatment with SY-1425, a retinoic acid receptor alpha (RARα) agonist.
The team discovered a subset of patients with acute myeloid leukemia (AML) who had a super-enhancer associated with the RARA gene, which is predictive of response to SY-1425.
The researchers also identified a subset of patients with myelodysplastic syndromes (MDS) who had high expression of the RARA gene.
And experiments showed that RARA-high MDS had a similar response to SY-1425 as that seen in AML driven by the RARA super-enhancer.
Ravindra Majeti MD, PhD, of Stanford University School of Medicine in California, and colleagues reported these findings in Cancer Discovery. Employees of Syros Pharmaceuticals, the company developing SY-1425, were also involved in this research.
In collaboration with the Majeti lab, Syros used its gene control platform to analyze 66 AML patients’ tumor samples. In this way, the researchers identified 6 distinct patient subsets based on super-enhancer profiles, including 1 enriched for a super-enhancer associated with the RARA gene.
The team found that super-enhancer profiles were strongly associated with survival outcomes, often independent of known genetic mutations in AML.
The RARA super-enhancer was associated with high expression of the RARA gene, which codes for a transcription factor targeted by SY-1425.
The RARA super-enhancer was predictive of response to SY-1425. In AML cells with high RARA expression, SY-1425 reduced proliferation and promoted differentiation.
Moreover, SY-1425 decreased tumor burden and prolonged survival in patient-derived xenograft models of AML with high RARA expression. However, there was no effect on AML cells or models with low RARA expression.
The researchers said SY-1425 induced profound transcriptional changes promoting cell differentiation in AML cells with high RARA expression, but the drug produced little to no transcriptional changes in AML cells with low RARA expression.
DHRS3 was the most strongly and rapidly induced gene in response to treatment with SY-1425. This led to the identification of DHRS3 induction as an early indicator of whether SY-1425 is affecting the targeted biology in defined subsets of AML and MDS patients. It is therefore used as a pharmacodynamic marker in the ongoing phase 2 trial of SY-1425.
In this trial, researchers are assessing the safety and efficacy of SY-1425 as a single agent in 4 AML and MDS patient populations, as well as testing SY-1425 in combination with azacitidine in newly diagnosed AML patients who are not suitable candidates for standard chemotherapy.
Predicting response to azacitidine in MDS
Research published in Cell Reports helps explain why some patients with myelodysplastic syndrome (MDS) do not respond to treatment with azacitidine.
The study showed that patients who were resistant to the drug had relatively quiescent hematopoietic progenitor cells (HPCs).
A smaller proportion of their HPCs were undergoing active cell-cycle progression when compared to the HPCs of patients who responded to azacitidine.
This discovery could provide the first method to identify non-responders to azacitidine early, according to study author Ashwin Unnikrishnan, PhD, of the University of New South Wales in Sydney, Australia.
“These are early days, but this could avoid what has really been a ‘wait and see’ approach with patients that sometimes results in them receiving futile treatment for 6 months,” Dr Unnikrishnan said.
“By that stage, the patient’s disease has progressed, and there’s no alternative for them.”
Dr Unnikrishnan and his colleagues also found the HPC quiescence in non-responders was mediated by integrin α5 (ITGA5) signaling, and the cells’ hematopoietic potential improved when the team combined azacitidine treatment with an ITGA5 inhibitor.
This suggests a potential avenue for future combination therapies that would improve azacitidine responsiveness.
Lastly, the researchers made discoveries that could explain why some patients who initially respond to azacitidine eventually relapse.
“All of the pernicious mutations that we associate with MDS never disappear in these patients, even after years of treatment,” Dr Unnikrishnan said. “From a clinical perspective, blood cell production is restored in patients, but they are a ticking time bomb, waiting to relapse.”
“[Azacitidine] is not a cure, and we are starting to understand why it does what it does. We need to find better treatments than azacitidine if we want a more durable therapy for MDS, and that’s the basis for our future work.”
Research published in Cell Reports helps explain why some patients with myelodysplastic syndrome (MDS) do not respond to treatment with azacitidine.
The study showed that patients who were resistant to the drug had relatively quiescent hematopoietic progenitor cells (HPCs).
A smaller proportion of their HPCs were undergoing active cell-cycle progression when compared to the HPCs of patients who responded to azacitidine.
This discovery could provide the first method to identify non-responders to azacitidine early, according to study author Ashwin Unnikrishnan, PhD, of the University of New South Wales in Sydney, Australia.
“These are early days, but this could avoid what has really been a ‘wait and see’ approach with patients that sometimes results in them receiving futile treatment for 6 months,” Dr Unnikrishnan said.
“By that stage, the patient’s disease has progressed, and there’s no alternative for them.”
Dr Unnikrishnan and his colleagues also found the HPC quiescence in non-responders was mediated by integrin α5 (ITGA5) signaling, and the cells’ hematopoietic potential improved when the team combined azacitidine treatment with an ITGA5 inhibitor.
This suggests a potential avenue for future combination therapies that would improve azacitidine responsiveness.
Lastly, the researchers made discoveries that could explain why some patients who initially respond to azacitidine eventually relapse.
“All of the pernicious mutations that we associate with MDS never disappear in these patients, even after years of treatment,” Dr Unnikrishnan said. “From a clinical perspective, blood cell production is restored in patients, but they are a ticking time bomb, waiting to relapse.”
“[Azacitidine] is not a cure, and we are starting to understand why it does what it does. We need to find better treatments than azacitidine if we want a more durable therapy for MDS, and that’s the basis for our future work.”
Research published in Cell Reports helps explain why some patients with myelodysplastic syndrome (MDS) do not respond to treatment with azacitidine.
The study showed that patients who were resistant to the drug had relatively quiescent hematopoietic progenitor cells (HPCs).
A smaller proportion of their HPCs were undergoing active cell-cycle progression when compared to the HPCs of patients who responded to azacitidine.
This discovery could provide the first method to identify non-responders to azacitidine early, according to study author Ashwin Unnikrishnan, PhD, of the University of New South Wales in Sydney, Australia.
“These are early days, but this could avoid what has really been a ‘wait and see’ approach with patients that sometimes results in them receiving futile treatment for 6 months,” Dr Unnikrishnan said.
“By that stage, the patient’s disease has progressed, and there’s no alternative for them.”
Dr Unnikrishnan and his colleagues also found the HPC quiescence in non-responders was mediated by integrin α5 (ITGA5) signaling, and the cells’ hematopoietic potential improved when the team combined azacitidine treatment with an ITGA5 inhibitor.
This suggests a potential avenue for future combination therapies that would improve azacitidine responsiveness.
Lastly, the researchers made discoveries that could explain why some patients who initially respond to azacitidine eventually relapse.
“All of the pernicious mutations that we associate with MDS never disappear in these patients, even after years of treatment,” Dr Unnikrishnan said. “From a clinical perspective, blood cell production is restored in patients, but they are a ticking time bomb, waiting to relapse.”
“[Azacitidine] is not a cure, and we are starting to understand why it does what it does. We need to find better treatments than azacitidine if we want a more durable therapy for MDS, and that’s the basis for our future work.”
FDA okays ClearLLab test for hematologic cancer detection
Beckman Coulter has been authorized to market its ClearLLab Reagents (T1, T2, B1, B2, M) tests for use with flow cytometry to detect leukemias, lymphomas, and myeloproliferative disorders in blood, bone marrow, and lymph nodes, according to the U.S. Food and Drug Administration.
A study evaluating the efficacy of the test compared the test results (n = 279) with clinical evaluations at four independent clinical sites. The results matched the diagnoses 93.4% of the time and correctly detected cancer 84.2% of the time.
“This represents a major step forward for the hematology-oncology community,” Alberto Gutierrez, PhD, of the FDA’s Center for Devices and Radiological Health said in the FDA’s release. “Laboratories and health care professionals now have access to an FDA-validated test that provides consistent results to aid in the diagnoses of these serious cancers.”
The approval coincides with criteria for ongoing evaluation of the ClearLLab tests and approval of future tests. The release notes that the ClearLLab test results must be reviewed by a trained professional.
Beckman Coulter has been authorized to market its ClearLLab Reagents (T1, T2, B1, B2, M) tests for use with flow cytometry to detect leukemias, lymphomas, and myeloproliferative disorders in blood, bone marrow, and lymph nodes, according to the U.S. Food and Drug Administration.
A study evaluating the efficacy of the test compared the test results (n = 279) with clinical evaluations at four independent clinical sites. The results matched the diagnoses 93.4% of the time and correctly detected cancer 84.2% of the time.
“This represents a major step forward for the hematology-oncology community,” Alberto Gutierrez, PhD, of the FDA’s Center for Devices and Radiological Health said in the FDA’s release. “Laboratories and health care professionals now have access to an FDA-validated test that provides consistent results to aid in the diagnoses of these serious cancers.”
The approval coincides with criteria for ongoing evaluation of the ClearLLab tests and approval of future tests. The release notes that the ClearLLab test results must be reviewed by a trained professional.
Beckman Coulter has been authorized to market its ClearLLab Reagents (T1, T2, B1, B2, M) tests for use with flow cytometry to detect leukemias, lymphomas, and myeloproliferative disorders in blood, bone marrow, and lymph nodes, according to the U.S. Food and Drug Administration.
A study evaluating the efficacy of the test compared the test results (n = 279) with clinical evaluations at four independent clinical sites. The results matched the diagnoses 93.4% of the time and correctly detected cancer 84.2% of the time.
“This represents a major step forward for the hematology-oncology community,” Alberto Gutierrez, PhD, of the FDA’s Center for Devices and Radiological Health said in the FDA’s release. “Laboratories and health care professionals now have access to an FDA-validated test that provides consistent results to aid in the diagnoses of these serious cancers.”
The approval coincides with criteria for ongoing evaluation of the ClearLLab tests and approval of future tests. The release notes that the ClearLLab test results must be reviewed by a trained professional.