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Two agents could take AML therapy in new directions
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—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—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.
Emicizumab granted priority review for hemophilia A without inhibitors
The US Food and Drug Administration (FDA) has granted priority review for emicizumab (Hemlibra®) for adults and children with hemophilia A without factor VIII inhibitors.
Earlier this year, the agency awarded emicizumab breakthrough therapy designation for the same population.
Emicizumab is a bispecific factor IXa- and factor X-directed antibody approved by the FDA for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and children who have hemophilia A with factor VIII inhibitors.
The FDA based its decision to grant emicizumab priority review on the phase 3 HAVEN 3 study, results of which were presented recently at the World Federation of Hemophilia congress.
In HAVEN 3, emicizumab demonstrated a 68% reduction (P<0.0001) in treated bleeds based on an intra-patient comparison in patients who were previously enrolled in a prospective non-interventional study.
According to Genentech, co-developer of the drug, this makes emicizumab the first medicine to show superior efficacy to prior treatment with factor VIII prophylaxis, the current standard of care for people with hemophilia A without factor VIII inhibitors.
About HAVEN 3
The randomized, multicenter, open-label trial evaluated prophylaxis versus no prophylaxis in patients without factor VIII inhibitors.
The study included 152 patients 12 years or older who were previously treated with factor VIII therapy on-demand or as prophylaxis.
Patients previously treated with on-demand factor VIII were randomized in a 2:2:1 fashion to 1 of 3 treatment groups:
- Arm A received emicizumab prophylaxis at 3 mg/kg/wk for 4 weeks, followed by 1.5 mg/kg/wk until the end of study.
- Arm B received emicizumab prophylaxis at 3 mg/kg/wk for 4 weeks, followed by 3 mg/kg/2wks for at least 24 weeks.
- Arm C received no prophylaxis
Patients previously treated prophylactically with factor VIII were enrolled in Arm D and received emicizumab prophylaxis at 3 mg/kg/wk for 4 weeks, followed by 1.5 mg/kg/wk until the end of study.
The protocol permitted episodic treatment of breakthrough bleeds with factor VIII therapy.
Patients in the prophylaxis groups achieved a 96% (P<0.0001) and 97% (P<0.0001) reduction in treated bleeds, respectively, compared to those who received no prophylaxis.
Additionally, 55.6% of patients treated weekly and 60% treated every 2 weeks had no treated bleeds. In contrast, 0% in the prophylaxis group achieved zero treated bleeds.
Investigators observed no unexpected or serious adverse events (AEs), no thrombotic events, and no cases of thrombotic microangiopathy.
The most common AEs occurring in 5% or more of patients were injection site reactions, arthralgia, nasopharyngitis, headache, upper respiratory tract infection, and influenza.
The FDA is expected to make a decision regarding approval by October 4.
The US Food and Drug Administration (FDA) has granted priority review for emicizumab (Hemlibra®) for adults and children with hemophilia A without factor VIII inhibitors.
Earlier this year, the agency awarded emicizumab breakthrough therapy designation for the same population.
Emicizumab is a bispecific factor IXa- and factor X-directed antibody approved by the FDA for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and children who have hemophilia A with factor VIII inhibitors.
The FDA based its decision to grant emicizumab priority review on the phase 3 HAVEN 3 study, results of which were presented recently at the World Federation of Hemophilia congress.
In HAVEN 3, emicizumab demonstrated a 68% reduction (P<0.0001) in treated bleeds based on an intra-patient comparison in patients who were previously enrolled in a prospective non-interventional study.
According to Genentech, co-developer of the drug, this makes emicizumab the first medicine to show superior efficacy to prior treatment with factor VIII prophylaxis, the current standard of care for people with hemophilia A without factor VIII inhibitors.
About HAVEN 3
The randomized, multicenter, open-label trial evaluated prophylaxis versus no prophylaxis in patients without factor VIII inhibitors.
The study included 152 patients 12 years or older who were previously treated with factor VIII therapy on-demand or as prophylaxis.
Patients previously treated with on-demand factor VIII were randomized in a 2:2:1 fashion to 1 of 3 treatment groups:
- Arm A received emicizumab prophylaxis at 3 mg/kg/wk for 4 weeks, followed by 1.5 mg/kg/wk until the end of study.
- Arm B received emicizumab prophylaxis at 3 mg/kg/wk for 4 weeks, followed by 3 mg/kg/2wks for at least 24 weeks.
- Arm C received no prophylaxis
Patients previously treated prophylactically with factor VIII were enrolled in Arm D and received emicizumab prophylaxis at 3 mg/kg/wk for 4 weeks, followed by 1.5 mg/kg/wk until the end of study.
The protocol permitted episodic treatment of breakthrough bleeds with factor VIII therapy.
Patients in the prophylaxis groups achieved a 96% (P<0.0001) and 97% (P<0.0001) reduction in treated bleeds, respectively, compared to those who received no prophylaxis.
Additionally, 55.6% of patients treated weekly and 60% treated every 2 weeks had no treated bleeds. In contrast, 0% in the prophylaxis group achieved zero treated bleeds.
Investigators observed no unexpected or serious adverse events (AEs), no thrombotic events, and no cases of thrombotic microangiopathy.
The most common AEs occurring in 5% or more of patients were injection site reactions, arthralgia, nasopharyngitis, headache, upper respiratory tract infection, and influenza.
The FDA is expected to make a decision regarding approval by October 4.
The US Food and Drug Administration (FDA) has granted priority review for emicizumab (Hemlibra®) for adults and children with hemophilia A without factor VIII inhibitors.
Earlier this year, the agency awarded emicizumab breakthrough therapy designation for the same population.
Emicizumab is a bispecific factor IXa- and factor X-directed antibody approved by the FDA for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and children who have hemophilia A with factor VIII inhibitors.
The FDA based its decision to grant emicizumab priority review on the phase 3 HAVEN 3 study, results of which were presented recently at the World Federation of Hemophilia congress.
In HAVEN 3, emicizumab demonstrated a 68% reduction (P<0.0001) in treated bleeds based on an intra-patient comparison in patients who were previously enrolled in a prospective non-interventional study.
According to Genentech, co-developer of the drug, this makes emicizumab the first medicine to show superior efficacy to prior treatment with factor VIII prophylaxis, the current standard of care for people with hemophilia A without factor VIII inhibitors.
About HAVEN 3
The randomized, multicenter, open-label trial evaluated prophylaxis versus no prophylaxis in patients without factor VIII inhibitors.
The study included 152 patients 12 years or older who were previously treated with factor VIII therapy on-demand or as prophylaxis.
Patients previously treated with on-demand factor VIII were randomized in a 2:2:1 fashion to 1 of 3 treatment groups:
- Arm A received emicizumab prophylaxis at 3 mg/kg/wk for 4 weeks, followed by 1.5 mg/kg/wk until the end of study.
- Arm B received emicizumab prophylaxis at 3 mg/kg/wk for 4 weeks, followed by 3 mg/kg/2wks for at least 24 weeks.
- Arm C received no prophylaxis
Patients previously treated prophylactically with factor VIII were enrolled in Arm D and received emicizumab prophylaxis at 3 mg/kg/wk for 4 weeks, followed by 1.5 mg/kg/wk until the end of study.
The protocol permitted episodic treatment of breakthrough bleeds with factor VIII therapy.
Patients in the prophylaxis groups achieved a 96% (P<0.0001) and 97% (P<0.0001) reduction in treated bleeds, respectively, compared to those who received no prophylaxis.
Additionally, 55.6% of patients treated weekly and 60% treated every 2 weeks had no treated bleeds. In contrast, 0% in the prophylaxis group achieved zero treated bleeds.
Investigators observed no unexpected or serious adverse events (AEs), no thrombotic events, and no cases of thrombotic microangiopathy.
The most common AEs occurring in 5% or more of patients were injection site reactions, arthralgia, nasopharyngitis, headache, upper respiratory tract infection, and influenza.
The FDA is expected to make a decision regarding approval by October 4.
Single-agent acalabrutinib ‘impressive’ in patients with WM
CHICAGO—Acalabrutinib monotherapy was highly effective in Waldenström’s macroglobulinemia (WM) in a phase 2 study, investigator Roger Owen, MD, reported at the 2018 ASCO Annual Meeting.
The BTK inhibitor was effective in both treatment-naïve and relapsed/refractory patients, with overall response rates for both groups in excess of 90%, and “amazing” major response rates—partial response or better—of approximately 80%, Dr Owen said.
Dr Owen, of the St James's Institute of Oncology, Leeds Teaching Hospitals NHS Trust in Leeds, UK, reported the findings as abstract 7501.*
Durations of response were excellent, according to Dr Owen, who also reported 2-year progression-free survival of 90% in treatment-naïve patients and 82% in relapsed/refractory patients.
The safety profile was favorable, with most adverse events of low grade, and a very limited number of dropouts due to adverse events, according to the investigator.
“I think this study clearly demonstrates the highly effective nature of acalabrutinib in Waldenström’s macroglobulinemia,” Dr Owen stated.
Acalabrutinib is a selective BTK inhibitor with minimal off-target activity, he said. The BTK inhibitor ibrutinib also has demonstrated activity in Waldenström’s, but has been associated with toxicities such as atrial fibrillation and bleeding, he noted.
In this phase 2 acalabrutinib study (NCT02180724), which included 14 treatment-naïve and 92 relapsed/refractory patients, atrial fibrillation occurred in 5 patients. However, 4 of those cases were grade 1-2, and only one was grade 3, according to Dr Owen.
Investigators observed grade 3 hypertension in 3 relapsed/refractory patients.
Bleeding events occurred in more than half of patients, though only 3 of those events were grade 3, and no patient discontinued treatment due to a bleeding episode.
These efficacy results are “impressive,” and the fact that very few cardiac events were seen is important, said Bruce D. Cheson, MD, of Georgetown University Medical Center in Washington, DC.
Dr Cheson commented on the acalabrutinib results in his presentation during ASCO on non-chemotherapy treatments for lymphoid malignancies.
“One can construct a non-chemo algorithm now for Waldenström’s, for patients who are MYD88 mutated, which is more than 90% of patients,” he said. “Right now ibrutinib, and perhaps in the future acalabrutinib, can be the initial therapy with or without rituximab based on the results of ongoing trials.”
However, single non-chemotherapy agents will not be sufficient to achieve cure of lymphoid malignancies, Dr Cheson added.
“We need to carefully develop rational combinations, identifying biomarkers for response, for resistance, for toxicity,” he said.
The study was sponsored by Acerta Pharma BV.
*Data presented at the meeting differ from the abstract.
CHICAGO—Acalabrutinib monotherapy was highly effective in Waldenström’s macroglobulinemia (WM) in a phase 2 study, investigator Roger Owen, MD, reported at the 2018 ASCO Annual Meeting.
The BTK inhibitor was effective in both treatment-naïve and relapsed/refractory patients, with overall response rates for both groups in excess of 90%, and “amazing” major response rates—partial response or better—of approximately 80%, Dr Owen said.
Dr Owen, of the St James's Institute of Oncology, Leeds Teaching Hospitals NHS Trust in Leeds, UK, reported the findings as abstract 7501.*
Durations of response were excellent, according to Dr Owen, who also reported 2-year progression-free survival of 90% in treatment-naïve patients and 82% in relapsed/refractory patients.
The safety profile was favorable, with most adverse events of low grade, and a very limited number of dropouts due to adverse events, according to the investigator.
“I think this study clearly demonstrates the highly effective nature of acalabrutinib in Waldenström’s macroglobulinemia,” Dr Owen stated.
Acalabrutinib is a selective BTK inhibitor with minimal off-target activity, he said. The BTK inhibitor ibrutinib also has demonstrated activity in Waldenström’s, but has been associated with toxicities such as atrial fibrillation and bleeding, he noted.
In this phase 2 acalabrutinib study (NCT02180724), which included 14 treatment-naïve and 92 relapsed/refractory patients, atrial fibrillation occurred in 5 patients. However, 4 of those cases were grade 1-2, and only one was grade 3, according to Dr Owen.
Investigators observed grade 3 hypertension in 3 relapsed/refractory patients.
Bleeding events occurred in more than half of patients, though only 3 of those events were grade 3, and no patient discontinued treatment due to a bleeding episode.
These efficacy results are “impressive,” and the fact that very few cardiac events were seen is important, said Bruce D. Cheson, MD, of Georgetown University Medical Center in Washington, DC.
Dr Cheson commented on the acalabrutinib results in his presentation during ASCO on non-chemotherapy treatments for lymphoid malignancies.
“One can construct a non-chemo algorithm now for Waldenström’s, for patients who are MYD88 mutated, which is more than 90% of patients,” he said. “Right now ibrutinib, and perhaps in the future acalabrutinib, can be the initial therapy with or without rituximab based on the results of ongoing trials.”
However, single non-chemotherapy agents will not be sufficient to achieve cure of lymphoid malignancies, Dr Cheson added.
“We need to carefully develop rational combinations, identifying biomarkers for response, for resistance, for toxicity,” he said.
The study was sponsored by Acerta Pharma BV.
*Data presented at the meeting differ from the abstract.
CHICAGO—Acalabrutinib monotherapy was highly effective in Waldenström’s macroglobulinemia (WM) in a phase 2 study, investigator Roger Owen, MD, reported at the 2018 ASCO Annual Meeting.
The BTK inhibitor was effective in both treatment-naïve and relapsed/refractory patients, with overall response rates for both groups in excess of 90%, and “amazing” major response rates—partial response or better—of approximately 80%, Dr Owen said.
Dr Owen, of the St James's Institute of Oncology, Leeds Teaching Hospitals NHS Trust in Leeds, UK, reported the findings as abstract 7501.*
Durations of response were excellent, according to Dr Owen, who also reported 2-year progression-free survival of 90% in treatment-naïve patients and 82% in relapsed/refractory patients.
The safety profile was favorable, with most adverse events of low grade, and a very limited number of dropouts due to adverse events, according to the investigator.
“I think this study clearly demonstrates the highly effective nature of acalabrutinib in Waldenström’s macroglobulinemia,” Dr Owen stated.
Acalabrutinib is a selective BTK inhibitor with minimal off-target activity, he said. The BTK inhibitor ibrutinib also has demonstrated activity in Waldenström’s, but has been associated with toxicities such as atrial fibrillation and bleeding, he noted.
In this phase 2 acalabrutinib study (NCT02180724), which included 14 treatment-naïve and 92 relapsed/refractory patients, atrial fibrillation occurred in 5 patients. However, 4 of those cases were grade 1-2, and only one was grade 3, according to Dr Owen.
Investigators observed grade 3 hypertension in 3 relapsed/refractory patients.
Bleeding events occurred in more than half of patients, though only 3 of those events were grade 3, and no patient discontinued treatment due to a bleeding episode.
These efficacy results are “impressive,” and the fact that very few cardiac events were seen is important, said Bruce D. Cheson, MD, of Georgetown University Medical Center in Washington, DC.
Dr Cheson commented on the acalabrutinib results in his presentation during ASCO on non-chemotherapy treatments for lymphoid malignancies.
“One can construct a non-chemo algorithm now for Waldenström’s, for patients who are MYD88 mutated, which is more than 90% of patients,” he said. “Right now ibrutinib, and perhaps in the future acalabrutinib, can be the initial therapy with or without rituximab based on the results of ongoing trials.”
However, single non-chemotherapy agents will not be sufficient to achieve cure of lymphoid malignancies, Dr Cheson added.
“We need to carefully develop rational combinations, identifying biomarkers for response, for resistance, for toxicity,” he said.
The study was sponsored by Acerta Pharma BV.
*Data presented at the meeting differ from the abstract.
Once-weekly carfilzomib combo improves PFS in R/R MM
CHICAGO—A once-weekly regimen of carfilzomib plus dexamethasone shows a favorable benefit-risk profile for patients with relapsed or refractory (R/R) multiple myeloma (MM), according to a new study.
“The more convenient dosing schedule can improve access to an efficacious therapy for patients unable to make twice-weekly visits to the clinic,” said investigator Maria-Victoria Mateos, MD, of the Hospital Clinico Universitario de Salamanca-IBSAL in Salamanca, Spain.
Dr Mateos presented results of the randomized, phase 3 study (abstract 8000) at the 2018 ASCO Annual Meeting. The results were also published in The Lancet.
Twice-weekly carfilzomib at 27 mg/m2 is approved as a single agent and in combination with lenalidomide or dexamethasone for the treatment of relapsed/refractory MM.
To develop a more convenient carfilzomib regimen, once-weekly carfilzomib plus dexamethasone was assessed in the phase 1/2 CHAMPION-1 study, showing good response rates (77%) and a median PFS of 12.6 months.
At ASCO, Dr Mateos presented the results from the pre-planned interim analysis of the phase 3 ARROW study (NCT02412878), comparing the two-drug regimen once-weekly vs twice-weekly.
Study design
The 478 patients, median age 66 years, had 2 to 3 prior therapies and prior exposure to a proteasome inhibitor and an immunomodulatory agent. Baseline characteristics were generally balanced, she said.
Investigators randomized patients to receive either once- or twice-weekly carfilzomib plus dexamethasone.
The once-weekly group received carfilzomib 20 mg/m2 intravenously on day 1 of cycle 1 and 70 mg/m2 on days 1, 8, and 15 of all subsequent cycles.
The twice-weekly group received the same carfilzomib dose on day 1, cycle 1 and 27 mg/m2 on days 8, 9, 15, and 16 thereafter. All patients received dexamethasone at 40 mg on days 1, 8, 15 (all cycles), and day 22 (cycles 1–9 only).
The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall response rate, overall survival, safety, and pharmacokinetics.
Results
The study met the primary endpoint of PFS, with a median PFS for the once-weekly dose of 11.2 months and 7.6 months for the twice-weekly dose.
In addition, “patients who received once-weekly carfilzomib plus dexamethasone achieved a statistically significant higher overall response rate (62.9%) than patients who received the twice-weekly dose (40.8%),” Dr Mateos said.
Similarly, more patients achieved a complete response or better (7.1%) with the once-weekly dose than the twice-weekly dose (1.7%).
Safety
The overall safety profile was comparable between the 2 treatment groups and no new safety risks were identified.
Grade 3 or higher adverse events occurred in 67.6% (once-weekly) and 61.7% (twice-weekly) of patients.
Treatment-related grade 5 adverse events occurred in 5 patients (2.1%) in the once-weekly group and in 2 patients (0.9%) in the twice-weekly group.
The incidence of grade 3 or higher hypertension and cardiac failure was similar in both groups.
“Exposure-adjusted incidence of grade 3 or higher adverse events was slightly higher in the once-weekly vs the twice-weekly group,” Dr Mateos explained, “but the exposure-adjusted incidence for severe adverse events and adverse events leading to discontinuation of carfilzomib or death were similar between the treatment groups,” she said.
The ARROW study was supported by Amgen Inc.
CHICAGO—A once-weekly regimen of carfilzomib plus dexamethasone shows a favorable benefit-risk profile for patients with relapsed or refractory (R/R) multiple myeloma (MM), according to a new study.
“The more convenient dosing schedule can improve access to an efficacious therapy for patients unable to make twice-weekly visits to the clinic,” said investigator Maria-Victoria Mateos, MD, of the Hospital Clinico Universitario de Salamanca-IBSAL in Salamanca, Spain.
Dr Mateos presented results of the randomized, phase 3 study (abstract 8000) at the 2018 ASCO Annual Meeting. The results were also published in The Lancet.
Twice-weekly carfilzomib at 27 mg/m2 is approved as a single agent and in combination with lenalidomide or dexamethasone for the treatment of relapsed/refractory MM.
To develop a more convenient carfilzomib regimen, once-weekly carfilzomib plus dexamethasone was assessed in the phase 1/2 CHAMPION-1 study, showing good response rates (77%) and a median PFS of 12.6 months.
At ASCO, Dr Mateos presented the results from the pre-planned interim analysis of the phase 3 ARROW study (NCT02412878), comparing the two-drug regimen once-weekly vs twice-weekly.
Study design
The 478 patients, median age 66 years, had 2 to 3 prior therapies and prior exposure to a proteasome inhibitor and an immunomodulatory agent. Baseline characteristics were generally balanced, she said.
Investigators randomized patients to receive either once- or twice-weekly carfilzomib plus dexamethasone.
The once-weekly group received carfilzomib 20 mg/m2 intravenously on day 1 of cycle 1 and 70 mg/m2 on days 1, 8, and 15 of all subsequent cycles.
The twice-weekly group received the same carfilzomib dose on day 1, cycle 1 and 27 mg/m2 on days 8, 9, 15, and 16 thereafter. All patients received dexamethasone at 40 mg on days 1, 8, 15 (all cycles), and day 22 (cycles 1–9 only).
The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall response rate, overall survival, safety, and pharmacokinetics.
Results
The study met the primary endpoint of PFS, with a median PFS for the once-weekly dose of 11.2 months and 7.6 months for the twice-weekly dose.
In addition, “patients who received once-weekly carfilzomib plus dexamethasone achieved a statistically significant higher overall response rate (62.9%) than patients who received the twice-weekly dose (40.8%),” Dr Mateos said.
Similarly, more patients achieved a complete response or better (7.1%) with the once-weekly dose than the twice-weekly dose (1.7%).
Safety
The overall safety profile was comparable between the 2 treatment groups and no new safety risks were identified.
Grade 3 or higher adverse events occurred in 67.6% (once-weekly) and 61.7% (twice-weekly) of patients.
Treatment-related grade 5 adverse events occurred in 5 patients (2.1%) in the once-weekly group and in 2 patients (0.9%) in the twice-weekly group.
The incidence of grade 3 or higher hypertension and cardiac failure was similar in both groups.
“Exposure-adjusted incidence of grade 3 or higher adverse events was slightly higher in the once-weekly vs the twice-weekly group,” Dr Mateos explained, “but the exposure-adjusted incidence for severe adverse events and adverse events leading to discontinuation of carfilzomib or death were similar between the treatment groups,” she said.
The ARROW study was supported by Amgen Inc.
CHICAGO—A once-weekly regimen of carfilzomib plus dexamethasone shows a favorable benefit-risk profile for patients with relapsed or refractory (R/R) multiple myeloma (MM), according to a new study.
“The more convenient dosing schedule can improve access to an efficacious therapy for patients unable to make twice-weekly visits to the clinic,” said investigator Maria-Victoria Mateos, MD, of the Hospital Clinico Universitario de Salamanca-IBSAL in Salamanca, Spain.
Dr Mateos presented results of the randomized, phase 3 study (abstract 8000) at the 2018 ASCO Annual Meeting. The results were also published in The Lancet.
Twice-weekly carfilzomib at 27 mg/m2 is approved as a single agent and in combination with lenalidomide or dexamethasone for the treatment of relapsed/refractory MM.
To develop a more convenient carfilzomib regimen, once-weekly carfilzomib plus dexamethasone was assessed in the phase 1/2 CHAMPION-1 study, showing good response rates (77%) and a median PFS of 12.6 months.
At ASCO, Dr Mateos presented the results from the pre-planned interim analysis of the phase 3 ARROW study (NCT02412878), comparing the two-drug regimen once-weekly vs twice-weekly.
Study design
The 478 patients, median age 66 years, had 2 to 3 prior therapies and prior exposure to a proteasome inhibitor and an immunomodulatory agent. Baseline characteristics were generally balanced, she said.
Investigators randomized patients to receive either once- or twice-weekly carfilzomib plus dexamethasone.
The once-weekly group received carfilzomib 20 mg/m2 intravenously on day 1 of cycle 1 and 70 mg/m2 on days 1, 8, and 15 of all subsequent cycles.
The twice-weekly group received the same carfilzomib dose on day 1, cycle 1 and 27 mg/m2 on days 8, 9, 15, and 16 thereafter. All patients received dexamethasone at 40 mg on days 1, 8, 15 (all cycles), and day 22 (cycles 1–9 only).
The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall response rate, overall survival, safety, and pharmacokinetics.
Results
The study met the primary endpoint of PFS, with a median PFS for the once-weekly dose of 11.2 months and 7.6 months for the twice-weekly dose.
In addition, “patients who received once-weekly carfilzomib plus dexamethasone achieved a statistically significant higher overall response rate (62.9%) than patients who received the twice-weekly dose (40.8%),” Dr Mateos said.
Similarly, more patients achieved a complete response or better (7.1%) with the once-weekly dose than the twice-weekly dose (1.7%).
Safety
The overall safety profile was comparable between the 2 treatment groups and no new safety risks were identified.
Grade 3 or higher adverse events occurred in 67.6% (once-weekly) and 61.7% (twice-weekly) of patients.
Treatment-related grade 5 adverse events occurred in 5 patients (2.1%) in the once-weekly group and in 2 patients (0.9%) in the twice-weekly group.
The incidence of grade 3 or higher hypertension and cardiac failure was similar in both groups.
“Exposure-adjusted incidence of grade 3 or higher adverse events was slightly higher in the once-weekly vs the twice-weekly group,” Dr Mateos explained, “but the exposure-adjusted incidence for severe adverse events and adverse events leading to discontinuation of carfilzomib or death were similar between the treatment groups,” she said.
The ARROW study was supported by Amgen Inc.
Encouraging early results for CB-derived NK cells in MM
CHICAGO—Cord blood (CB) is a viable source of natural killer (NK) cells for adoptive cellular therapy for multiple myeloma (MM), according to a speaker at the 2018 ASCO Annual Meeting.
Ex-vivo expanded cord blood NK cells were well tolerated without significant graft-versus-host disease (GVHD) or cytokine release syndrome (CRS) in a phase 2 study.
Nina Shah, MD, of the University of California San Francisco, reported these results as abstract 8006.*
The phase 2 study (NCT01729091) included 33 patients with symptomatic MM who were appropriate candidates for autologous stem cell transplant (ASCT).
For each patient, investigators chose cord blood units with at least a 4/6 match at HLA-A, -B and –DR.
Prior to the autologous graft, patients received lenalidomide and melphalan. Lenalidomide was given based on preclinical data suggesting synergy between that immunomodulatory agent and NK cells, Dr Shah said.
Patients were a median age of 59 (range, 25 – 72), 36% had a history of progressive disease or relapse, and 73% had adverse cytogenetics/FISH, were ISS III, or had a history of progressive disease or relapse.
Results
Dr Shah observed that in a generally high-risk population, responses to treatment with cord blood NK cells in the setting of ASCT were “encouraging,” with 79% of patients achieving very good partial response (VGPR) or better.
Twenty-one patients (64%) achieved a complete response (CR) or near CR. And 61% achieved minimal residual disease (MRD) negativity by day 100.
Patients had an estimated 3-year progression-free survival of 52%.
Three patients died, all from disease progression, and 13 patients have progressed.
The investigators observed no infusional toxicities, no GVHD, no CRS, and no neurotoxicity.
One patient experienced graft failure and was rescued with an autologous back-up graft.
"We are able to detect the donor-derived NK cells up to 13 days after infusion,” Dr Shah said, “but I think a more sensitive analysis with flow chimerism will not only allow us to detect more patients, but also better interrogate them to truly understand the in vivo phenotype and activation status of these cells."
Dr Shah indicated she and her colleagues became interested in studying cord blood for NK cell therapy because it is a known source of hematopoietic cells that is immediately available, does not require donor manipulation, and has more flexibility in genetic matching.
Previously, Dr Shah and colleagues conducted a phase 1 study, in which 12 patients received cord blood NK cells up to a dose of 1 x 108 NK cells/kg. “This was determined to be adequate and safe to move on to the phase 2,” she said.
Despite encouraging results, more research needs to be done, according to Dr Shah. “I don't think this is the end-all, be-all for NK cell therapy.”
Some future directions include combination with antibody therapy, improving NK persistence in vivo using cytokine manipulation, and possibly engineering chimeric antigen receptor (CAR)-modified NK cells, Dr Shah observed.
It’s also possible that HLA match may not be needed: “If that is the case, we will truly have an off-the-shelf source of NK cells that we can apply more readily to various patients,” she said.
The study was supported by Celgene Corporation, Stading-Younger Cancer Research Foundation, and the MD Anderson High-Risk Multiple Myeloma Moonshot Project.
*Data in the presentation differ from the abstract.
CHICAGO—Cord blood (CB) is a viable source of natural killer (NK) cells for adoptive cellular therapy for multiple myeloma (MM), according to a speaker at the 2018 ASCO Annual Meeting.
Ex-vivo expanded cord blood NK cells were well tolerated without significant graft-versus-host disease (GVHD) or cytokine release syndrome (CRS) in a phase 2 study.
Nina Shah, MD, of the University of California San Francisco, reported these results as abstract 8006.*
The phase 2 study (NCT01729091) included 33 patients with symptomatic MM who were appropriate candidates for autologous stem cell transplant (ASCT).
For each patient, investigators chose cord blood units with at least a 4/6 match at HLA-A, -B and –DR.
Prior to the autologous graft, patients received lenalidomide and melphalan. Lenalidomide was given based on preclinical data suggesting synergy between that immunomodulatory agent and NK cells, Dr Shah said.
Patients were a median age of 59 (range, 25 – 72), 36% had a history of progressive disease or relapse, and 73% had adverse cytogenetics/FISH, were ISS III, or had a history of progressive disease or relapse.
Results
Dr Shah observed that in a generally high-risk population, responses to treatment with cord blood NK cells in the setting of ASCT were “encouraging,” with 79% of patients achieving very good partial response (VGPR) or better.
Twenty-one patients (64%) achieved a complete response (CR) or near CR. And 61% achieved minimal residual disease (MRD) negativity by day 100.
Patients had an estimated 3-year progression-free survival of 52%.
Three patients died, all from disease progression, and 13 patients have progressed.
The investigators observed no infusional toxicities, no GVHD, no CRS, and no neurotoxicity.
One patient experienced graft failure and was rescued with an autologous back-up graft.
"We are able to detect the donor-derived NK cells up to 13 days after infusion,” Dr Shah said, “but I think a more sensitive analysis with flow chimerism will not only allow us to detect more patients, but also better interrogate them to truly understand the in vivo phenotype and activation status of these cells."
Dr Shah indicated she and her colleagues became interested in studying cord blood for NK cell therapy because it is a known source of hematopoietic cells that is immediately available, does not require donor manipulation, and has more flexibility in genetic matching.
Previously, Dr Shah and colleagues conducted a phase 1 study, in which 12 patients received cord blood NK cells up to a dose of 1 x 108 NK cells/kg. “This was determined to be adequate and safe to move on to the phase 2,” she said.
Despite encouraging results, more research needs to be done, according to Dr Shah. “I don't think this is the end-all, be-all for NK cell therapy.”
Some future directions include combination with antibody therapy, improving NK persistence in vivo using cytokine manipulation, and possibly engineering chimeric antigen receptor (CAR)-modified NK cells, Dr Shah observed.
It’s also possible that HLA match may not be needed: “If that is the case, we will truly have an off-the-shelf source of NK cells that we can apply more readily to various patients,” she said.
The study was supported by Celgene Corporation, Stading-Younger Cancer Research Foundation, and the MD Anderson High-Risk Multiple Myeloma Moonshot Project.
*Data in the presentation differ from the abstract.
CHICAGO—Cord blood (CB) is a viable source of natural killer (NK) cells for adoptive cellular therapy for multiple myeloma (MM), according to a speaker at the 2018 ASCO Annual Meeting.
Ex-vivo expanded cord blood NK cells were well tolerated without significant graft-versus-host disease (GVHD) or cytokine release syndrome (CRS) in a phase 2 study.
Nina Shah, MD, of the University of California San Francisco, reported these results as abstract 8006.*
The phase 2 study (NCT01729091) included 33 patients with symptomatic MM who were appropriate candidates for autologous stem cell transplant (ASCT).
For each patient, investigators chose cord blood units with at least a 4/6 match at HLA-A, -B and –DR.
Prior to the autologous graft, patients received lenalidomide and melphalan. Lenalidomide was given based on preclinical data suggesting synergy between that immunomodulatory agent and NK cells, Dr Shah said.
Patients were a median age of 59 (range, 25 – 72), 36% had a history of progressive disease or relapse, and 73% had adverse cytogenetics/FISH, were ISS III, or had a history of progressive disease or relapse.
Results
Dr Shah observed that in a generally high-risk population, responses to treatment with cord blood NK cells in the setting of ASCT were “encouraging,” with 79% of patients achieving very good partial response (VGPR) or better.
Twenty-one patients (64%) achieved a complete response (CR) or near CR. And 61% achieved minimal residual disease (MRD) negativity by day 100.
Patients had an estimated 3-year progression-free survival of 52%.
Three patients died, all from disease progression, and 13 patients have progressed.
The investigators observed no infusional toxicities, no GVHD, no CRS, and no neurotoxicity.
One patient experienced graft failure and was rescued with an autologous back-up graft.
"We are able to detect the donor-derived NK cells up to 13 days after infusion,” Dr Shah said, “but I think a more sensitive analysis with flow chimerism will not only allow us to detect more patients, but also better interrogate them to truly understand the in vivo phenotype and activation status of these cells."
Dr Shah indicated she and her colleagues became interested in studying cord blood for NK cell therapy because it is a known source of hematopoietic cells that is immediately available, does not require donor manipulation, and has more flexibility in genetic matching.
Previously, Dr Shah and colleagues conducted a phase 1 study, in which 12 patients received cord blood NK cells up to a dose of 1 x 108 NK cells/kg. “This was determined to be adequate and safe to move on to the phase 2,” she said.
Despite encouraging results, more research needs to be done, according to Dr Shah. “I don't think this is the end-all, be-all for NK cell therapy.”
Some future directions include combination with antibody therapy, improving NK persistence in vivo using cytokine manipulation, and possibly engineering chimeric antigen receptor (CAR)-modified NK cells, Dr Shah observed.
It’s also possible that HLA match may not be needed: “If that is the case, we will truly have an off-the-shelf source of NK cells that we can apply more readily to various patients,” she said.
The study was supported by Celgene Corporation, Stading-Younger Cancer Research Foundation, and the MD Anderson High-Risk Multiple Myeloma Moonshot Project.
*Data in the presentation differ from the abstract.
CAR T-cell technology making headway in MM
Chimeric antigen receptor (CAR) T-cell technology has been successfully used in the treatment of hematologic malignancies such as leukemias and lymphomas. Now, this technology has come to the forefront in multiple myeloma (MM).
Researchers at the National Cancer Institute, led by James N. Kochenderfer, MD, generated CAR T cells expressing the B-cell maturation antigen (BCMA), which is uniquely found on MM cells.
In the first in humans study, 24 patients received CAR-BCMA T cells at doses ranging between 0.3 and 3 x 106 CAR+ T cells/kg. Sixteen patients were treated at the highest dose. These patients had a median of 9.5 lines of prior therapy and 63% were refractory to their last treatment.
Thirteen patients had responses that were either partial or better and the overall response rate was 81%. Median event-free survival was 31 weeks. At the time of the report, 6 patients still have ongoing responses.
Patient cases
The report highlights a case study of a patient who had a large abdominal mass that resolved on computed tomography imaging, with λ light chains decreasing dramatically and becoming undetectable after CAR T-cell infusion. Recovery of normal plasma cells was noticeable with λ chain increases, but the ratio of κ to λ ratio remained normal 6 months after CAR T-cell infusion.
Using immunohistochemistry staining of CS138 before and 2 months after CAR-BMCA infusion, the researchers found effective depletion in bone marrow plasma cells in patients who were evaluated.
In patients who responded to treatment, decline in serum BCMA was also observed. However, in a patient who later progressed, BCMA increases were seen, leading the researchers to suggest that BCMA may be a tumor marker for MM.
The researchers noted that peak levels of CAR T cells occurred between 7 and 14 days after infusion and highest levels were seen in patients who showed antimyeloma responses.
Toxicity
CAR T-cell technology is also associated with accompanying toxicities.
At the highest dose, cytokine release syndrome (CRS) was a substantial toxicity especially in 2 patients who had a significant MM burden: in one case 80% of bone marrow cells were MM plasma cells and in the other the MM burden was 90%.
Six of the 16 patients required vasopressor support for hypotension and 1 patient required mechanical ventilation. The researchers noted that CRS of grade 3/4 was seen in patients who had a higher MM plasma cell burden.
The researchers indicated there is room for improvement. “The importance of persistence of CAR T cells in treating MM requires additional study,” they stated.
The sometimes low or absence of BCMA expression on MM cells may prompt the search for other antigens. “Treatment outcomes varied substantially between patients, and much room for improvement remains in improving the durability of antimyeloma responses and in reducing toxicity,” they concluded.
The researchers reported their findings in the Journal of Clinical Oncology.
Chimeric antigen receptor (CAR) T-cell technology has been successfully used in the treatment of hematologic malignancies such as leukemias and lymphomas. Now, this technology has come to the forefront in multiple myeloma (MM).
Researchers at the National Cancer Institute, led by James N. Kochenderfer, MD, generated CAR T cells expressing the B-cell maturation antigen (BCMA), which is uniquely found on MM cells.
In the first in humans study, 24 patients received CAR-BCMA T cells at doses ranging between 0.3 and 3 x 106 CAR+ T cells/kg. Sixteen patients were treated at the highest dose. These patients had a median of 9.5 lines of prior therapy and 63% were refractory to their last treatment.
Thirteen patients had responses that were either partial or better and the overall response rate was 81%. Median event-free survival was 31 weeks. At the time of the report, 6 patients still have ongoing responses.
Patient cases
The report highlights a case study of a patient who had a large abdominal mass that resolved on computed tomography imaging, with λ light chains decreasing dramatically and becoming undetectable after CAR T-cell infusion. Recovery of normal plasma cells was noticeable with λ chain increases, but the ratio of κ to λ ratio remained normal 6 months after CAR T-cell infusion.
Using immunohistochemistry staining of CS138 before and 2 months after CAR-BMCA infusion, the researchers found effective depletion in bone marrow plasma cells in patients who were evaluated.
In patients who responded to treatment, decline in serum BCMA was also observed. However, in a patient who later progressed, BCMA increases were seen, leading the researchers to suggest that BCMA may be a tumor marker for MM.
The researchers noted that peak levels of CAR T cells occurred between 7 and 14 days after infusion and highest levels were seen in patients who showed antimyeloma responses.
Toxicity
CAR T-cell technology is also associated with accompanying toxicities.
At the highest dose, cytokine release syndrome (CRS) was a substantial toxicity especially in 2 patients who had a significant MM burden: in one case 80% of bone marrow cells were MM plasma cells and in the other the MM burden was 90%.
Six of the 16 patients required vasopressor support for hypotension and 1 patient required mechanical ventilation. The researchers noted that CRS of grade 3/4 was seen in patients who had a higher MM plasma cell burden.
The researchers indicated there is room for improvement. “The importance of persistence of CAR T cells in treating MM requires additional study,” they stated.
The sometimes low or absence of BCMA expression on MM cells may prompt the search for other antigens. “Treatment outcomes varied substantially between patients, and much room for improvement remains in improving the durability of antimyeloma responses and in reducing toxicity,” they concluded.
The researchers reported their findings in the Journal of Clinical Oncology.
Chimeric antigen receptor (CAR) T-cell technology has been successfully used in the treatment of hematologic malignancies such as leukemias and lymphomas. Now, this technology has come to the forefront in multiple myeloma (MM).
Researchers at the National Cancer Institute, led by James N. Kochenderfer, MD, generated CAR T cells expressing the B-cell maturation antigen (BCMA), which is uniquely found on MM cells.
In the first in humans study, 24 patients received CAR-BCMA T cells at doses ranging between 0.3 and 3 x 106 CAR+ T cells/kg. Sixteen patients were treated at the highest dose. These patients had a median of 9.5 lines of prior therapy and 63% were refractory to their last treatment.
Thirteen patients had responses that were either partial or better and the overall response rate was 81%. Median event-free survival was 31 weeks. At the time of the report, 6 patients still have ongoing responses.
Patient cases
The report highlights a case study of a patient who had a large abdominal mass that resolved on computed tomography imaging, with λ light chains decreasing dramatically and becoming undetectable after CAR T-cell infusion. Recovery of normal plasma cells was noticeable with λ chain increases, but the ratio of κ to λ ratio remained normal 6 months after CAR T-cell infusion.
Using immunohistochemistry staining of CS138 before and 2 months after CAR-BMCA infusion, the researchers found effective depletion in bone marrow plasma cells in patients who were evaluated.
In patients who responded to treatment, decline in serum BCMA was also observed. However, in a patient who later progressed, BCMA increases were seen, leading the researchers to suggest that BCMA may be a tumor marker for MM.
The researchers noted that peak levels of CAR T cells occurred between 7 and 14 days after infusion and highest levels were seen in patients who showed antimyeloma responses.
Toxicity
CAR T-cell technology is also associated with accompanying toxicities.
At the highest dose, cytokine release syndrome (CRS) was a substantial toxicity especially in 2 patients who had a significant MM burden: in one case 80% of bone marrow cells were MM plasma cells and in the other the MM burden was 90%.
Six of the 16 patients required vasopressor support for hypotension and 1 patient required mechanical ventilation. The researchers noted that CRS of grade 3/4 was seen in patients who had a higher MM plasma cell burden.
The researchers indicated there is room for improvement. “The importance of persistence of CAR T cells in treating MM requires additional study,” they stated.
The sometimes low or absence of BCMA expression on MM cells may prompt the search for other antigens. “Treatment outcomes varied substantially between patients, and much room for improvement remains in improving the durability of antimyeloma responses and in reducing toxicity,” they concluded.
The researchers reported their findings in the Journal of Clinical Oncology.
FDA approves first biosimilar pegfilgrastim
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.
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.
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.
Over 1100 new meds, vaccines being developed to treat cancer
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.”
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.”
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.”
Eltrombopag receives priority review designation for SAA
Eltrombopag (Promacta®) in combination with standard immunosuppressive therapy (IST) has received priority review designation from the US Food and Drug Administration (FDA) for first-line treatment of severe aplastic anemia (SAA).
The drug is already approved for SAA in the refractory setting for patients who have had an insufficient response to IST.
And it is approved for adults and children with chronic immune thrombocytopenia (ITP) who are refractory to other treatments and for patients with chronic hepatitis C virus infection who are thrombocytopenic.
Eltrombopag, an oral thrombopoietin receptor agonist, had received breakthrough therapy designation from the FDA earlier this year for use in combination with IST as first-line treatment of SAA.
The priority review designation for the agent as a first-line treatment for SAA is supported by data from a phase 1/2 trial published in NEJM in April 2017 and subsequent data on file with Novartis.
The FDA intends 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.
Trial data
Ninety-two patients with previously untreated SAA were enrolled on the trial and received IST and eltrombopag in 3 different cohorts.
Cohorts varied by start day of eltrombopag and duration of eltrombopag therapy. Patients in cohort 1 received eltrombopag from day 14 to 6 months. Patients in cohort 2 received the drug from day 14 to 3 months. And patients in cohort 3 received eltrombopag from day 1 to 6 months.
The overall response rate (ORR) at 6 months was 80% (cohort 1), 87% (cohort 2), and 94% (cohort 3).
The complete response rate at 6 months was 33%, 26%, and 58% in the 3 cohorts, respectively.
At a median follow-up of 2 years, the overall survival rate was 97%.
In the corporate announcement of the priority review designation, Novartis reported an ORR of 85% at 6 months.
Adverse events included transient elevations in liver enzyme levels (7 patients) and 2 severe adverse events—grades 2 and 3 cutaneous eruption—related to eltrombopag that resulted in patients stopping the drug.
Eltrombopag is marketed as Revolade in countries outside the US.
Eltrombopag (Promacta®) in combination with standard immunosuppressive therapy (IST) has received priority review designation from the US Food and Drug Administration (FDA) for first-line treatment of severe aplastic anemia (SAA).
The drug is already approved for SAA in the refractory setting for patients who have had an insufficient response to IST.
And it is approved for adults and children with chronic immune thrombocytopenia (ITP) who are refractory to other treatments and for patients with chronic hepatitis C virus infection who are thrombocytopenic.
Eltrombopag, an oral thrombopoietin receptor agonist, had received breakthrough therapy designation from the FDA earlier this year for use in combination with IST as first-line treatment of SAA.
The priority review designation for the agent as a first-line treatment for SAA is supported by data from a phase 1/2 trial published in NEJM in April 2017 and subsequent data on file with Novartis.
The FDA intends 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.
Trial data
Ninety-two patients with previously untreated SAA were enrolled on the trial and received IST and eltrombopag in 3 different cohorts.
Cohorts varied by start day of eltrombopag and duration of eltrombopag therapy. Patients in cohort 1 received eltrombopag from day 14 to 6 months. Patients in cohort 2 received the drug from day 14 to 3 months. And patients in cohort 3 received eltrombopag from day 1 to 6 months.
The overall response rate (ORR) at 6 months was 80% (cohort 1), 87% (cohort 2), and 94% (cohort 3).
The complete response rate at 6 months was 33%, 26%, and 58% in the 3 cohorts, respectively.
At a median follow-up of 2 years, the overall survival rate was 97%.
In the corporate announcement of the priority review designation, Novartis reported an ORR of 85% at 6 months.
Adverse events included transient elevations in liver enzyme levels (7 patients) and 2 severe adverse events—grades 2 and 3 cutaneous eruption—related to eltrombopag that resulted in patients stopping the drug.
Eltrombopag is marketed as Revolade in countries outside the US.
Eltrombopag (Promacta®) in combination with standard immunosuppressive therapy (IST) has received priority review designation from the US Food and Drug Administration (FDA) for first-line treatment of severe aplastic anemia (SAA).
The drug is already approved for SAA in the refractory setting for patients who have had an insufficient response to IST.
And it is approved for adults and children with chronic immune thrombocytopenia (ITP) who are refractory to other treatments and for patients with chronic hepatitis C virus infection who are thrombocytopenic.
Eltrombopag, an oral thrombopoietin receptor agonist, had received breakthrough therapy designation from the FDA earlier this year for use in combination with IST as first-line treatment of SAA.
The priority review designation for the agent as a first-line treatment for SAA is supported by data from a phase 1/2 trial published in NEJM in April 2017 and subsequent data on file with Novartis.
The FDA intends 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.
Trial data
Ninety-two patients with previously untreated SAA were enrolled on the trial and received IST and eltrombopag in 3 different cohorts.
Cohorts varied by start day of eltrombopag and duration of eltrombopag therapy. Patients in cohort 1 received eltrombopag from day 14 to 6 months. Patients in cohort 2 received the drug from day 14 to 3 months. And patients in cohort 3 received eltrombopag from day 1 to 6 months.
The overall response rate (ORR) at 6 months was 80% (cohort 1), 87% (cohort 2), and 94% (cohort 3).
The complete response rate at 6 months was 33%, 26%, and 58% in the 3 cohorts, respectively.
At a median follow-up of 2 years, the overall survival rate was 97%.
In the corporate announcement of the priority review designation, Novartis reported an ORR of 85% at 6 months.
Adverse events included transient elevations in liver enzyme levels (7 patients) and 2 severe adverse events—grades 2 and 3 cutaneous eruption—related to eltrombopag that resulted in patients stopping the drug.
Eltrombopag is marketed as Revolade in countries outside the US.
Cytotect®CP found to be safe and effective after allo-HCT
A small retrospective study of 23 transplant patients has confirmed that CMV hyperimmune globulin (Cytotect®CP) is a safe and effective salvage therapy for patients with cytomegalovirus (CMV) infection after allogeneic hematopoietic cell transplant (allo-HCT).
Cytotect®CP used as salvage therapy resulted in a 78% overall response rate and 70% of all patients cleared CMV infection, according to investigators.
They observed no clinically significant adverse events.
CMV is a major factor contributing to high mortality rates in allo-HCT patients.
And because Cytotect®CP is less toxic than commonly used treatments for CMV infection, investigators suggested that it be used prophylactically in patients known to have a predisposition to CMV infection.
They reported their findings in the journal Bone Marrow Transplantation.
Patient characteristics and methods
All 23 patients transplanted at 8 centers in France were CMV seropositive at the time of transplant, and 70% received the transplant from a CMV serostatus negative donor.
Recipient positivity and donor negativity, the investigators indicated, is a risk factor for developing recurrent CMV infection after allo-HCT.
The patients’ median age was 53, 11 were male and 12 female.
Five patients (22%) received a haploidentical transplant and 14 (61%) from an unrelated donor, which the investigators pointed out is also a known risk factor for developing recurrent CMV infection.
Thirteen (57%) were in complete remission from their underlying disease, 4 (17%) in partial remission, 1 (4%) had stable disease, and 5 (22%) were in relapse or had progressive disease.
Most (83%) had a peripheral blood transplant, 15 (65%) had a reduced intensity conditioning regimen, and 16 (70%) had antithymocyte globulin as part of their conditioning regimen.
All patients received valacyclovir as antiviral prophylaxis prior to receiving Cytotect®CP. The investigators mentioned in the paper that valacyclovir has not been proven to be effective in treating CMV.
They noted that other CMV treatments, such as ganciclovir, foscavir, and dicofovir, cause high levels of toxicity, frequently leading to treatment discontinuation.
Seventeen patients (74%) had a history of graft-versus-host disease (GVHD), and 11 (49%) had active GVHD at the time CMV hyperimmune globulin was administered.
Investigators used quantitative polymerase chain reaction (PCR) to quantify CMV viral load in the blood.
Treatment could begin when patients’ viral load was greater than 3-3.5 log UI/mL, according to the Francophone Society of Bone Marrow Transplantation and Cellular therapy.
Three patients received Cytotect®CP at a prophylaxis dose (200 U/kg/week) to prevent CMV recurrences and 20 as preemptive therapy (400 U/kg on days 1, 4, 8 then 200 U/kg on days 12and 16).
Seven patients (30%) received Cytotect®CP as monotherapy, 5 (22%) in combination with ganciclovir, 5 (22%) in combination with foscavir, 2 (9%) in combination with ganciclovir and foscavir, and 4 (17%) with some other combination.
Investigators restricted their analysis to 100-day overall survival (OS), starting at the beginning of Cytotect®CP treatment to death within 100 days, regardless of the cause of death.
Results
Eighteen patients (78%) responded to Cytotect®CP, and 16 of the responders converted to CMV-PCR negative.
Median time to achieve CMV-PCR response was 15 days (range, 3-51).
Four patients did not respond to therapy, and 1 patient had a non-evaluable response. The latter patient died 13 days after the introduction of Cytotect®CP due to another infection.
Eight patients died within 100 days after initiation of Cytotect®CP. Two deaths were related to CMV and 6 were unrelated.
Four patients who responded to Cytotect®CP experienced CMV relapse between 9 and 49 days after their best response to therapy.
Five responders died within 100 days due to the following causes: GVHD (n = 2), other infection (n = 1), underlying disease (n = 1), and CMV-related causes (n = 1).
Two of the 4 nonresponders died of other infection (n = 1) and GVHD (n = 1).
Investigators estimated the 100-day OS from the start of Cytotect®CP to be 69.6%. They observed no statistical difference (P=0.258) between those who responded (73.7%) and those who didn’t (50.0%).
The investigators believe that Cytotect®CP is an alternative option for treatment of CMV infection because it avoids renal and bone marrow impairment and should be considered as prophylaxis in select patients.
They recommend a large prospective study be conducted to confirm safety and efficacy results of CMV hyperimmune globulin.
Cytotect®CP is authorized in more than 15 countries for the prophylaxis of CMV infection in patients receiving immunosuppressive treatment, particularly transplant recipients.
In French transplant centers, according to the study authors, use of Cytotect®CP is limited to the salvage setting for recurrent or refractory CMV infections and sometimes in combination for CMV pneumonia.
Biotest, the commercializer of Cytotect®CP, provided a grant for this study.
A small retrospective study of 23 transplant patients has confirmed that CMV hyperimmune globulin (Cytotect®CP) is a safe and effective salvage therapy for patients with cytomegalovirus (CMV) infection after allogeneic hematopoietic cell transplant (allo-HCT).
Cytotect®CP used as salvage therapy resulted in a 78% overall response rate and 70% of all patients cleared CMV infection, according to investigators.
They observed no clinically significant adverse events.
CMV is a major factor contributing to high mortality rates in allo-HCT patients.
And because Cytotect®CP is less toxic than commonly used treatments for CMV infection, investigators suggested that it be used prophylactically in patients known to have a predisposition to CMV infection.
They reported their findings in the journal Bone Marrow Transplantation.
Patient characteristics and methods
All 23 patients transplanted at 8 centers in France were CMV seropositive at the time of transplant, and 70% received the transplant from a CMV serostatus negative donor.
Recipient positivity and donor negativity, the investigators indicated, is a risk factor for developing recurrent CMV infection after allo-HCT.
The patients’ median age was 53, 11 were male and 12 female.
Five patients (22%) received a haploidentical transplant and 14 (61%) from an unrelated donor, which the investigators pointed out is also a known risk factor for developing recurrent CMV infection.
Thirteen (57%) were in complete remission from their underlying disease, 4 (17%) in partial remission, 1 (4%) had stable disease, and 5 (22%) were in relapse or had progressive disease.
Most (83%) had a peripheral blood transplant, 15 (65%) had a reduced intensity conditioning regimen, and 16 (70%) had antithymocyte globulin as part of their conditioning regimen.
All patients received valacyclovir as antiviral prophylaxis prior to receiving Cytotect®CP. The investigators mentioned in the paper that valacyclovir has not been proven to be effective in treating CMV.
They noted that other CMV treatments, such as ganciclovir, foscavir, and dicofovir, cause high levels of toxicity, frequently leading to treatment discontinuation.
Seventeen patients (74%) had a history of graft-versus-host disease (GVHD), and 11 (49%) had active GVHD at the time CMV hyperimmune globulin was administered.
Investigators used quantitative polymerase chain reaction (PCR) to quantify CMV viral load in the blood.
Treatment could begin when patients’ viral load was greater than 3-3.5 log UI/mL, according to the Francophone Society of Bone Marrow Transplantation and Cellular therapy.
Three patients received Cytotect®CP at a prophylaxis dose (200 U/kg/week) to prevent CMV recurrences and 20 as preemptive therapy (400 U/kg on days 1, 4, 8 then 200 U/kg on days 12and 16).
Seven patients (30%) received Cytotect®CP as monotherapy, 5 (22%) in combination with ganciclovir, 5 (22%) in combination with foscavir, 2 (9%) in combination with ganciclovir and foscavir, and 4 (17%) with some other combination.
Investigators restricted their analysis to 100-day overall survival (OS), starting at the beginning of Cytotect®CP treatment to death within 100 days, regardless of the cause of death.
Results
Eighteen patients (78%) responded to Cytotect®CP, and 16 of the responders converted to CMV-PCR negative.
Median time to achieve CMV-PCR response was 15 days (range, 3-51).
Four patients did not respond to therapy, and 1 patient had a non-evaluable response. The latter patient died 13 days after the introduction of Cytotect®CP due to another infection.
Eight patients died within 100 days after initiation of Cytotect®CP. Two deaths were related to CMV and 6 were unrelated.
Four patients who responded to Cytotect®CP experienced CMV relapse between 9 and 49 days after their best response to therapy.
Five responders died within 100 days due to the following causes: GVHD (n = 2), other infection (n = 1), underlying disease (n = 1), and CMV-related causes (n = 1).
Two of the 4 nonresponders died of other infection (n = 1) and GVHD (n = 1).
Investigators estimated the 100-day OS from the start of Cytotect®CP to be 69.6%. They observed no statistical difference (P=0.258) between those who responded (73.7%) and those who didn’t (50.0%).
The investigators believe that Cytotect®CP is an alternative option for treatment of CMV infection because it avoids renal and bone marrow impairment and should be considered as prophylaxis in select patients.
They recommend a large prospective study be conducted to confirm safety and efficacy results of CMV hyperimmune globulin.
Cytotect®CP is authorized in more than 15 countries for the prophylaxis of CMV infection in patients receiving immunosuppressive treatment, particularly transplant recipients.
In French transplant centers, according to the study authors, use of Cytotect®CP is limited to the salvage setting for recurrent or refractory CMV infections and sometimes in combination for CMV pneumonia.
Biotest, the commercializer of Cytotect®CP, provided a grant for this study.
A small retrospective study of 23 transplant patients has confirmed that CMV hyperimmune globulin (Cytotect®CP) is a safe and effective salvage therapy for patients with cytomegalovirus (CMV) infection after allogeneic hematopoietic cell transplant (allo-HCT).
Cytotect®CP used as salvage therapy resulted in a 78% overall response rate and 70% of all patients cleared CMV infection, according to investigators.
They observed no clinically significant adverse events.
CMV is a major factor contributing to high mortality rates in allo-HCT patients.
And because Cytotect®CP is less toxic than commonly used treatments for CMV infection, investigators suggested that it be used prophylactically in patients known to have a predisposition to CMV infection.
They reported their findings in the journal Bone Marrow Transplantation.
Patient characteristics and methods
All 23 patients transplanted at 8 centers in France were CMV seropositive at the time of transplant, and 70% received the transplant from a CMV serostatus negative donor.
Recipient positivity and donor negativity, the investigators indicated, is a risk factor for developing recurrent CMV infection after allo-HCT.
The patients’ median age was 53, 11 were male and 12 female.
Five patients (22%) received a haploidentical transplant and 14 (61%) from an unrelated donor, which the investigators pointed out is also a known risk factor for developing recurrent CMV infection.
Thirteen (57%) were in complete remission from their underlying disease, 4 (17%) in partial remission, 1 (4%) had stable disease, and 5 (22%) were in relapse or had progressive disease.
Most (83%) had a peripheral blood transplant, 15 (65%) had a reduced intensity conditioning regimen, and 16 (70%) had antithymocyte globulin as part of their conditioning regimen.
All patients received valacyclovir as antiviral prophylaxis prior to receiving Cytotect®CP. The investigators mentioned in the paper that valacyclovir has not been proven to be effective in treating CMV.
They noted that other CMV treatments, such as ganciclovir, foscavir, and dicofovir, cause high levels of toxicity, frequently leading to treatment discontinuation.
Seventeen patients (74%) had a history of graft-versus-host disease (GVHD), and 11 (49%) had active GVHD at the time CMV hyperimmune globulin was administered.
Investigators used quantitative polymerase chain reaction (PCR) to quantify CMV viral load in the blood.
Treatment could begin when patients’ viral load was greater than 3-3.5 log UI/mL, according to the Francophone Society of Bone Marrow Transplantation and Cellular therapy.
Three patients received Cytotect®CP at a prophylaxis dose (200 U/kg/week) to prevent CMV recurrences and 20 as preemptive therapy (400 U/kg on days 1, 4, 8 then 200 U/kg on days 12and 16).
Seven patients (30%) received Cytotect®CP as monotherapy, 5 (22%) in combination with ganciclovir, 5 (22%) in combination with foscavir, 2 (9%) in combination with ganciclovir and foscavir, and 4 (17%) with some other combination.
Investigators restricted their analysis to 100-day overall survival (OS), starting at the beginning of Cytotect®CP treatment to death within 100 days, regardless of the cause of death.
Results
Eighteen patients (78%) responded to Cytotect®CP, and 16 of the responders converted to CMV-PCR negative.
Median time to achieve CMV-PCR response was 15 days (range, 3-51).
Four patients did not respond to therapy, and 1 patient had a non-evaluable response. The latter patient died 13 days after the introduction of Cytotect®CP due to another infection.
Eight patients died within 100 days after initiation of Cytotect®CP. Two deaths were related to CMV and 6 were unrelated.
Four patients who responded to Cytotect®CP experienced CMV relapse between 9 and 49 days after their best response to therapy.
Five responders died within 100 days due to the following causes: GVHD (n = 2), other infection (n = 1), underlying disease (n = 1), and CMV-related causes (n = 1).
Two of the 4 nonresponders died of other infection (n = 1) and GVHD (n = 1).
Investigators estimated the 100-day OS from the start of Cytotect®CP to be 69.6%. They observed no statistical difference (P=0.258) between those who responded (73.7%) and those who didn’t (50.0%).
The investigators believe that Cytotect®CP is an alternative option for treatment of CMV infection because it avoids renal and bone marrow impairment and should be considered as prophylaxis in select patients.
They recommend a large prospective study be conducted to confirm safety and efficacy results of CMV hyperimmune globulin.
Cytotect®CP is authorized in more than 15 countries for the prophylaxis of CMV infection in patients receiving immunosuppressive treatment, particularly transplant recipients.
In French transplant centers, according to the study authors, use of Cytotect®CP is limited to the salvage setting for recurrent or refractory CMV infections and sometimes in combination for CMV pneumonia.
Biotest, the commercializer of Cytotect®CP, provided a grant for this study.