Multiple Myeloma

Photo from Flickr

The US Food and Drug Administration (FDA) has granted orphan drug designation to SRF231 for the treatment of multiple myeloma (MM).

SRF231 is a fully human antibody that inhibits the activity of CD47, a protein that is overexpressed on many cancer cells and prevents them from being engulfed and eliminated by macrophages.

Surface Oncology, the company developing SRF231, is currently conducting a phase 1 trial (NCT03512340) of SRF231 in patients with solid tumors and hematologic malignancies.

Preclinical research on SRF231 was presented at the 2016 ASH Annual Meeting.

SRF231 demonstrated “potent” activity against hematologic malignancies, according to researchers.

The team said SRF231 promoted macrophage-mediated phagocytic clearance of several hematologic primary tumor samples and cell lines in vitro.

SRF231 also demonstrated activity in murine xenograft models of hematologic malignancies. Specifically, the researchers observed “profound tumor growth inhibition” in models of MM, diffuse large B-cell lymphoma, and Burkitt lymphoma.

The team said SRF231 demonstrated activity when given alone or in combination with opsonizing antibodies.

Results also showed that SRF231 did not induce hemagglutination or phagocytosis of red blood cells in vitro.

About orphan designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

Orphan designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

Photo from Flickr

The US Food and Drug Administration (FDA) has granted orphan drug designation to SRF231 for the treatment of multiple myeloma (MM).

SRF231 is a fully human antibody that inhibits the activity of CD47, a protein that is overexpressed on many cancer cells and prevents them from being engulfed and eliminated by macrophages.

Surface Oncology, the company developing SRF231, is currently conducting a phase 1 trial (NCT03512340) of SRF231 in patients with solid tumors and hematologic malignancies.

Preclinical research on SRF231 was presented at the 2016 ASH Annual Meeting.

SRF231 demonstrated “potent” activity against hematologic malignancies, according to researchers.

The team said SRF231 promoted macrophage-mediated phagocytic clearance of several hematologic primary tumor samples and cell lines in vitro.

SRF231 also demonstrated activity in murine xenograft models of hematologic malignancies. Specifically, the researchers observed “profound tumor growth inhibition” in models of MM, diffuse large B-cell lymphoma, and Burkitt lymphoma.

The team said SRF231 demonstrated activity when given alone or in combination with opsonizing antibodies.

Results also showed that SRF231 did not induce hemagglutination or phagocytosis of red blood cells in vitro.

About orphan designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

Orphan designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

Photo from Flickr

The US Food and Drug Administration (FDA) has granted orphan drug designation to SRF231 for the treatment of multiple myeloma (MM).

SRF231 is a fully human antibody that inhibits the activity of CD47, a protein that is overexpressed on many cancer cells and prevents them from being engulfed and eliminated by macrophages.

Surface Oncology, the company developing SRF231, is currently conducting a phase 1 trial (NCT03512340) of SRF231 in patients with solid tumors and hematologic malignancies.

Preclinical research on SRF231 was presented at the 2016 ASH Annual Meeting.

SRF231 demonstrated “potent” activity against hematologic malignancies, according to researchers.

The team said SRF231 promoted macrophage-mediated phagocytic clearance of several hematologic primary tumor samples and cell lines in vitro.

SRF231 also demonstrated activity in murine xenograft models of hematologic malignancies. Specifically, the researchers observed “profound tumor growth inhibition” in models of MM, diffuse large B-cell lymphoma, and Burkitt lymphoma.

The team said SRF231 demonstrated activity when given alone or in combination with opsonizing antibodies.

Results also showed that SRF231 did not induce hemagglutination or phagocytosis of red blood cells in vitro.

About orphan designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

Orphan designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

Photo courtesy of Celgene

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval for Lenalidomide Accord as a treatment for multiple myeloma (MM).

Lenalidomide Accord is a generic version of the immunomodulatory agent Revlimid, which has been authorized in the European Union since June 2007.

The CHMP said studies have demonstrated the satisfactory quality of Lenalidomide Accord and its bioequivalence to Revlimid.

The CHMP’s recommendation for Lenalidomide Accord will be reviewed by the European Commission, which has the authority to approve medicines for use in the European Union, Norway, Iceland, and Liechtenstein.

The European Commission usually makes a decision within 67 days of the CHMP’s recommendation.

If approved, Lenalidomide Accord will be available as capsules (2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg, 20 mg, and 25 mg) and authorized for the following uses:

• As monotherapy for the maintenance treatment of adults with newly diagnosed MM who have undergone autologous stem cell transplant
• In combination with melphalan and prednisone followed by lenalidomide maintenance in adults with previously untreated MM who are not eligible for transplant
• In combination with dexamethasone to treat MM in adults who have received at least 1 prior therapy.

The applicant for Lenalidomide Accord is Accord Healthcare Limited.

Photo courtesy of Celgene

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval for Lenalidomide Accord as a treatment for multiple myeloma (MM).

Lenalidomide Accord is a generic version of the immunomodulatory agent Revlimid, which has been authorized in the European Union since June 2007.

The CHMP said studies have demonstrated the satisfactory quality of Lenalidomide Accord and its bioequivalence to Revlimid.

The CHMP’s recommendation for Lenalidomide Accord will be reviewed by the European Commission, which has the authority to approve medicines for use in the European Union, Norway, Iceland, and Liechtenstein.

The European Commission usually makes a decision within 67 days of the CHMP’s recommendation.

If approved, Lenalidomide Accord will be available as capsules (2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg, 20 mg, and 25 mg) and authorized for the following uses:

• As monotherapy for the maintenance treatment of adults with newly diagnosed MM who have undergone autologous stem cell transplant
• In combination with melphalan and prednisone followed by lenalidomide maintenance in adults with previously untreated MM who are not eligible for transplant
• In combination with dexamethasone to treat MM in adults who have received at least 1 prior therapy.

The applicant for Lenalidomide Accord is Accord Healthcare Limited.

Photo courtesy of Celgene

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval for Lenalidomide Accord as a treatment for multiple myeloma (MM).

Lenalidomide Accord is a generic version of the immunomodulatory agent Revlimid, which has been authorized in the European Union since June 2007.

The CHMP said studies have demonstrated the satisfactory quality of Lenalidomide Accord and its bioequivalence to Revlimid.

The CHMP’s recommendation for Lenalidomide Accord will be reviewed by the European Commission, which has the authority to approve medicines for use in the European Union, Norway, Iceland, and Liechtenstein.

The European Commission usually makes a decision within 67 days of the CHMP’s recommendation.

If approved, Lenalidomide Accord will be available as capsules (2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg, 20 mg, and 25 mg) and authorized for the following uses:

• As monotherapy for the maintenance treatment of adults with newly diagnosed MM who have undergone autologous stem cell transplant
• In combination with melphalan and prednisone followed by lenalidomide maintenance in adults with previously untreated MM who are not eligible for transplant
• In combination with dexamethasone to treat MM in adults who have received at least 1 prior therapy.

The applicant for Lenalidomide Accord is Accord Healthcare Limited.

With the help of gene expression signatures, a simulated treatment learning model identified which patients with multiple myeloma would benefit most from treatment with bortezomib or lenalidomide, researchers reported in Nature Communications.

The study included 910 participants across three phase 3 trials. In all, 20% would have a 100% greater-than-average progression-free survival (PFS) benefit from bortezomib, while 31% would have a 200% greater-than-average PFS benefit from lenalidomide, wrote Joske Ubels of University Center Utrecht, the Netherlands, and her colleagues.

The genetic heterogeneity of cancer and risk of treatment necessitate tools that “predict – at the moment of diagnosis – which patients will benefit most from a certain treatment,” the researchers wrote. While gene expression signatures can predict a favorable or adverse prognosis, they do not account for the effect of treatment on survival.

“The key idea of simulated treatment learning is that a patient’s treatment benefit can be estimated by comparing [his or her] survival to a set of genetically similar patients [who] received the comparator treatment,” they noted.

To do so, the researchers applied an algorithm called GESTURE to combined data from the TT2 (Total Therapy 2 for Multiple Myeloma), TT3, and HOVON-65/GMMG-HD4 trials. These trials compared bortezomib or lenalidomide with conventional therapies for multiple myeloma. The model identified 180 patients (20%) for whom bortezomib would produce a 100% greater PFS benefit than in the study population as a whole. Conversely, lenalidomide would produce a 200% greater PFS benefit in 31% of patients.

The simulated treatment learning model “can derive clinically actionable gene expression signatures that enable a more personalized approach to treatment,” the researchers concluded. The method requires a large dataset but could be useful for trials that have missed their primary endpoint, such as the CheckMate-026 trial of nivolumab. The next step is to see if the model makes useful treatment predictions for other cancers. The code needed to train and validate the model is available at github.com/jubels/GESTURE.

The Van Herk Fellowship provided support. The lenalidomide dataset was created as part of the Multiple Myeloma Research Foundation Personalized Medicine Initiative. Dr. Ubels and one coinvestigator are employees of SkylineDx; another coinvestigator served on its advisory board. The others reported having no relevant conflicts of interest.

SOURCE: Ubels J et al. Nat Commun. 2018 Jul 27. doi: 10.1038/s41467-018-05348-5.

With the help of gene expression signatures, a simulated treatment learning model identified which patients with multiple myeloma would benefit most from treatment with bortezomib or lenalidomide, researchers reported in Nature Communications.

The study included 910 participants across three phase 3 trials. In all, 20% would have a 100% greater-than-average progression-free survival (PFS) benefit from bortezomib, while 31% would have a 200% greater-than-average PFS benefit from lenalidomide, wrote Joske Ubels of University Center Utrecht, the Netherlands, and her colleagues.

The genetic heterogeneity of cancer and risk of treatment necessitate tools that “predict – at the moment of diagnosis – which patients will benefit most from a certain treatment,” the researchers wrote. While gene expression signatures can predict a favorable or adverse prognosis, they do not account for the effect of treatment on survival.

“The key idea of simulated treatment learning is that a patient’s treatment benefit can be estimated by comparing [his or her] survival to a set of genetically similar patients [who] received the comparator treatment,” they noted.

To do so, the researchers applied an algorithm called GESTURE to combined data from the TT2 (Total Therapy 2 for Multiple Myeloma), TT3, and HOVON-65/GMMG-HD4 trials. These trials compared bortezomib or lenalidomide with conventional therapies for multiple myeloma. The model identified 180 patients (20%) for whom bortezomib would produce a 100% greater PFS benefit than in the study population as a whole. Conversely, lenalidomide would produce a 200% greater PFS benefit in 31% of patients.

The simulated treatment learning model “can derive clinically actionable gene expression signatures that enable a more personalized approach to treatment,” the researchers concluded. The method requires a large dataset but could be useful for trials that have missed their primary endpoint, such as the CheckMate-026 trial of nivolumab. The next step is to see if the model makes useful treatment predictions for other cancers. The code needed to train and validate the model is available at github.com/jubels/GESTURE.

The Van Herk Fellowship provided support. The lenalidomide dataset was created as part of the Multiple Myeloma Research Foundation Personalized Medicine Initiative. Dr. Ubels and one coinvestigator are employees of SkylineDx; another coinvestigator served on its advisory board. The others reported having no relevant conflicts of interest.

SOURCE: Ubels J et al. Nat Commun. 2018 Jul 27. doi: 10.1038/s41467-018-05348-5.

With the help of gene expression signatures, a simulated treatment learning model identified which patients with multiple myeloma would benefit most from treatment with bortezomib or lenalidomide, researchers reported in Nature Communications.

The study included 910 participants across three phase 3 trials. In all, 20% would have a 100% greater-than-average progression-free survival (PFS) benefit from bortezomib, while 31% would have a 200% greater-than-average PFS benefit from lenalidomide, wrote Joske Ubels of University Center Utrecht, the Netherlands, and her colleagues.

The genetic heterogeneity of cancer and risk of treatment necessitate tools that “predict – at the moment of diagnosis – which patients will benefit most from a certain treatment,” the researchers wrote. While gene expression signatures can predict a favorable or adverse prognosis, they do not account for the effect of treatment on survival.

“The key idea of simulated treatment learning is that a patient’s treatment benefit can be estimated by comparing [his or her] survival to a set of genetically similar patients [who] received the comparator treatment,” they noted.

To do so, the researchers applied an algorithm called GESTURE to combined data from the TT2 (Total Therapy 2 for Multiple Myeloma), TT3, and HOVON-65/GMMG-HD4 trials. These trials compared bortezomib or lenalidomide with conventional therapies for multiple myeloma. The model identified 180 patients (20%) for whom bortezomib would produce a 100% greater PFS benefit than in the study population as a whole. Conversely, lenalidomide would produce a 200% greater PFS benefit in 31% of patients.

The simulated treatment learning model “can derive clinically actionable gene expression signatures that enable a more personalized approach to treatment,” the researchers concluded. The method requires a large dataset but could be useful for trials that have missed their primary endpoint, such as the CheckMate-026 trial of nivolumab. The next step is to see if the model makes useful treatment predictions for other cancers. The code needed to train and validate the model is available at github.com/jubels/GESTURE.

The Van Herk Fellowship provided support. The lenalidomide dataset was created as part of the Multiple Myeloma Research Foundation Personalized Medicine Initiative. Dr. Ubels and one coinvestigator are employees of SkylineDx; another coinvestigator served on its advisory board. The others reported having no relevant conflicts of interest.

SOURCE: Ubels J et al. Nat Commun. 2018 Jul 27. doi: 10.1038/s41467-018-05348-5.

Photo courtesy of Janssen

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended broadening the existing marketing authorization for daratumumab (Darzalex).

The CHMP is recommending approval for daratumumab in combination with bortezomib, melphalan, and prednisone (VMP) for the treatment of adults with newly diagnosed multiple myeloma (MM) who are ineligible for autologous stem cell transplant.

The CHMP’s recommendation will be reviewed by the European Commission (EC), which has the authority to approve medicines for use in the European Union, Norway, Iceland, and Liechtenstein.

The EC usually makes a decision within 67 days of the CHMP’s recommendation.

Daratumumab already has EC approval for the following indications:

• For use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, to treat adults with MM who have received at least 1 prior therapy
• As monotherapy for adults with relapsed and refractory MM whose prior therapy included a proteasome inhibitor and an immunomodulatory agent and who have demonstrated disease progression on their last therapy.

The CHMP’s recommendation to expand the existing marketing authorization for daratumumab is based on results from the phase 3 ALCYONE (MMY3007) study.

Results from this study were presented at the 2017 ASH Annual Meeting and simultaneously published in NEJM.

ALCYONE enrolled 706 patients with newly diagnosed MM who were not eligible for high-dose chemotherapy with autologous stem cell transplant. Patients were randomized to receive VMP or daratumumab plus VMP (D-VMP).

The overall response rates were 91% in the D-VMP arm and 74% in the VMP arm (P<0.0001). Rates of complete response were 43% and 24%, respectively. Rates of minimal residual disease negativity were 22% and 6%, respectively.

The median progression-free survival (PFS) was not reached in the D-VMP arm and was 18.1 months in the VMP arm. The 12-month PFS was 87% and 76%, respectively. The 18-month PFS was 72% and 50%, respectively.

The most common treatment-emergent adverse events (in the D-VMP and VMP arms, respectively) were neutropenia (50% and 53%), thrombocytopenia (49% and 54%), anemia (28% and 38%), peripheral sensory neuropathy (28% and 34%), upper respiratory tract infection (26% and 14%), diarrhea (24% and 25%), pyrexia (23% and 21%), and nausea (21% and 22%).

Infusion-related reactions occurred in 28% of patients in the D-VMP arm and 0% of those in the VMP arm.

The rate of grade 3/4 infections was higher in the D-VMP arm than the VMP arm—23% and 15%, respectively. In both arms, most infections resolved.

The most common grade 3/4 treatment-emergent adverse events (in the D-VMP and VMP arms, respectively) were neutropenia (40% and 39%), thrombocytopenia (34% and 38%), and anemia (16% and 20%).

The rate of discontinuation due to adverse events was 5% in the D-VMP arm and 9% in the VMP arm.

Photo courtesy of Janssen

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended broadening the existing marketing authorization for daratumumab (Darzalex).

The CHMP is recommending approval for daratumumab in combination with bortezomib, melphalan, and prednisone (VMP) for the treatment of adults with newly diagnosed multiple myeloma (MM) who are ineligible for autologous stem cell transplant.

The CHMP’s recommendation will be reviewed by the European Commission (EC), which has the authority to approve medicines for use in the European Union, Norway, Iceland, and Liechtenstein.

The EC usually makes a decision within 67 days of the CHMP’s recommendation.

Daratumumab already has EC approval for the following indications:

• For use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, to treat adults with MM who have received at least 1 prior therapy
• As monotherapy for adults with relapsed and refractory MM whose prior therapy included a proteasome inhibitor and an immunomodulatory agent and who have demonstrated disease progression on their last therapy.

The CHMP’s recommendation to expand the existing marketing authorization for daratumumab is based on results from the phase 3 ALCYONE (MMY3007) study.

Results from this study were presented at the 2017 ASH Annual Meeting and simultaneously published in NEJM.

ALCYONE enrolled 706 patients with newly diagnosed MM who were not eligible for high-dose chemotherapy with autologous stem cell transplant. Patients were randomized to receive VMP or daratumumab plus VMP (D-VMP).

The overall response rates were 91% in the D-VMP arm and 74% in the VMP arm (P<0.0001). Rates of complete response were 43% and 24%, respectively. Rates of minimal residual disease negativity were 22% and 6%, respectively.

The median progression-free survival (PFS) was not reached in the D-VMP arm and was 18.1 months in the VMP arm. The 12-month PFS was 87% and 76%, respectively. The 18-month PFS was 72% and 50%, respectively.

The most common treatment-emergent adverse events (in the D-VMP and VMP arms, respectively) were neutropenia (50% and 53%), thrombocytopenia (49% and 54%), anemia (28% and 38%), peripheral sensory neuropathy (28% and 34%), upper respiratory tract infection (26% and 14%), diarrhea (24% and 25%), pyrexia (23% and 21%), and nausea (21% and 22%).

Infusion-related reactions occurred in 28% of patients in the D-VMP arm and 0% of those in the VMP arm.

The rate of grade 3/4 infections was higher in the D-VMP arm than the VMP arm—23% and 15%, respectively. In both arms, most infections resolved.

The most common grade 3/4 treatment-emergent adverse events (in the D-VMP and VMP arms, respectively) were neutropenia (40% and 39%), thrombocytopenia (34% and 38%), and anemia (16% and 20%).

The rate of discontinuation due to adverse events was 5% in the D-VMP arm and 9% in the VMP arm.

Photo courtesy of Janssen

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended broadening the existing marketing authorization for daratumumab (Darzalex).

The CHMP is recommending approval for daratumumab in combination with bortezomib, melphalan, and prednisone (VMP) for the treatment of adults with newly diagnosed multiple myeloma (MM) who are ineligible for autologous stem cell transplant.

The CHMP’s recommendation will be reviewed by the European Commission (EC), which has the authority to approve medicines for use in the European Union, Norway, Iceland, and Liechtenstein.

The EC usually makes a decision within 67 days of the CHMP’s recommendation.

Daratumumab already has EC approval for the following indications:

• For use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, to treat adults with MM who have received at least 1 prior therapy
• As monotherapy for adults with relapsed and refractory MM whose prior therapy included a proteasome inhibitor and an immunomodulatory agent and who have demonstrated disease progression on their last therapy.

The CHMP’s recommendation to expand the existing marketing authorization for daratumumab is based on results from the phase 3 ALCYONE (MMY3007) study.

Results from this study were presented at the 2017 ASH Annual Meeting and simultaneously published in NEJM.

ALCYONE enrolled 706 patients with newly diagnosed MM who were not eligible for high-dose chemotherapy with autologous stem cell transplant. Patients were randomized to receive VMP or daratumumab plus VMP (D-VMP).

The overall response rates were 91% in the D-VMP arm and 74% in the VMP arm (P<0.0001). Rates of complete response were 43% and 24%, respectively. Rates of minimal residual disease negativity were 22% and 6%, respectively.

The median progression-free survival (PFS) was not reached in the D-VMP arm and was 18.1 months in the VMP arm. The 12-month PFS was 87% and 76%, respectively. The 18-month PFS was 72% and 50%, respectively.

The most common treatment-emergent adverse events (in the D-VMP and VMP arms, respectively) were neutropenia (50% and 53%), thrombocytopenia (49% and 54%), anemia (28% and 38%), peripheral sensory neuropathy (28% and 34%), upper respiratory tract infection (26% and 14%), diarrhea (24% and 25%), pyrexia (23% and 21%), and nausea (21% and 22%).

Infusion-related reactions occurred in 28% of patients in the D-VMP arm and 0% of those in the VMP arm.

The rate of grade 3/4 infections was higher in the D-VMP arm than the VMP arm—23% and 15%, respectively. In both arms, most infections resolved.

The most common grade 3/4 treatment-emergent adverse events (in the D-VMP and VMP arms, respectively) were neutropenia (40% and 39%), thrombocytopenia (34% and 38%), and anemia (16% and 20%).

The rate of discontinuation due to adverse events was 5% in the D-VMP arm and 9% in the VMP arm.

Photo from Amgen

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval for 2 pegfilgrastim biosimilar candidates—Udenyca and Pelgraz.

Both products have been deemed highly similar to the reference product, Neulasta, a growth-colony-stimulating factor intended to reduce the duration of neutropenia and the incidence of febrile neutropenia due to chemotherapy.

The CHMP’s recommendations for Pelgraz and Udenyca will be reviewed by the European Commission, which has the authority to approve medicines for use in the European Union, Norway, Iceland, and Liechtenstein.

The European Commission usually makes a decision within 67 days of the CHMP’s recommendation.

If approved, Udenyca and Pelgraz will be available as 6 mg solutions for injection.

The full indication for both products will be to reduce the duration of neutropenia and the incidence of febrile neutropenia in adults receiving cytotoxic chemotherapy for malignancies, except chronic myeloid leukemia and myelodysplastic syndromes.

The CHMP said data have shown that Pelgraz and Udenyca both have comparable quality, safety, and efficacy to Neulasta.

Pelgraz’s marketing authorization application is supported by data from a phase 1 pharmacokinetic (PK) and pharmacodynamic (PD) study in healthy volunteers and a phase 3 study of breast cancer patients receiving docetaxel, doxorubicin, and cyclophosphamide.

Results from the phase 1 study were published in Clinical Pharmacology in Drug Development in 2016.

Udenyca’s marketing authorization application is supported by data from an immunogenicity study as well as a PK/PD study comparing Udenyca (formerly CHS-1701) and Neulasta in healthy subjects.

Results from the PK/PD trial were presented at the 2017 ASCO Annual Meeting.

The applicant for Udenyca is ERA Consulting GmbH. The applicant for Pelgraz is Accord Healthcare Limited (the international arm of Intas Pharmaceuticals Ltd).

Photo from Amgen

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval for 2 pegfilgrastim biosimilar candidates—Udenyca and Pelgraz.

Both products have been deemed highly similar to the reference product, Neulasta, a growth-colony-stimulating factor intended to reduce the duration of neutropenia and the incidence of febrile neutropenia due to chemotherapy.

The CHMP’s recommendations for Pelgraz and Udenyca will be reviewed by the European Commission, which has the authority to approve medicines for use in the European Union, Norway, Iceland, and Liechtenstein.

The European Commission usually makes a decision within 67 days of the CHMP’s recommendation.

If approved, Udenyca and Pelgraz will be available as 6 mg solutions for injection.

The full indication for both products will be to reduce the duration of neutropenia and the incidence of febrile neutropenia in adults receiving cytotoxic chemotherapy for malignancies, except chronic myeloid leukemia and myelodysplastic syndromes.

The CHMP said data have shown that Pelgraz and Udenyca both have comparable quality, safety, and efficacy to Neulasta.

Pelgraz’s marketing authorization application is supported by data from a phase 1 pharmacokinetic (PK) and pharmacodynamic (PD) study in healthy volunteers and a phase 3 study of breast cancer patients receiving docetaxel, doxorubicin, and cyclophosphamide.

Results from the phase 1 study were published in Clinical Pharmacology in Drug Development in 2016.

Udenyca’s marketing authorization application is supported by data from an immunogenicity study as well as a PK/PD study comparing Udenyca (formerly CHS-1701) and Neulasta in healthy subjects.

Results from the PK/PD trial were presented at the 2017 ASCO Annual Meeting.

The applicant for Udenyca is ERA Consulting GmbH. The applicant for Pelgraz is Accord Healthcare Limited (the international arm of Intas Pharmaceuticals Ltd).

Photo from Amgen

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval for 2 pegfilgrastim biosimilar candidates—Udenyca and Pelgraz.

Both products have been deemed highly similar to the reference product, Neulasta, a growth-colony-stimulating factor intended to reduce the duration of neutropenia and the incidence of febrile neutropenia due to chemotherapy.

The CHMP’s recommendations for Pelgraz and Udenyca will be reviewed by the European Commission, which has the authority to approve medicines for use in the European Union, Norway, Iceland, and Liechtenstein.

The European Commission usually makes a decision within 67 days of the CHMP’s recommendation.

If approved, Udenyca and Pelgraz will be available as 6 mg solutions for injection.

The full indication for both products will be to reduce the duration of neutropenia and the incidence of febrile neutropenia in adults receiving cytotoxic chemotherapy for malignancies, except chronic myeloid leukemia and myelodysplastic syndromes.

The CHMP said data have shown that Pelgraz and Udenyca both have comparable quality, safety, and efficacy to Neulasta.

Pelgraz’s marketing authorization application is supported by data from a phase 1 pharmacokinetic (PK) and pharmacodynamic (PD) study in healthy volunteers and a phase 3 study of breast cancer patients receiving docetaxel, doxorubicin, and cyclophosphamide.

Results from the phase 1 study were published in Clinical Pharmacology in Drug Development in 2016.

Udenyca’s marketing authorization application is supported by data from an immunogenicity study as well as a PK/PD study comparing Udenyca (formerly CHS-1701) and Neulasta in healthy subjects.

Results from the PK/PD trial were presented at the 2017 ASCO Annual Meeting.

The applicant for Udenyca is ERA Consulting GmbH. The applicant for Pelgraz is Accord Healthcare Limited (the international arm of Intas Pharmaceuticals Ltd).

Photo by Rhoda Baer

Research has shown an increase in the global incidence of leukemia and non-Hodgkin lymphoma (NHL) in recent years.

The Global Burden of Disease (GBD) study showed that, from 2006 to 2016, the incidence of NHL increased 45%, and the incidence of leukemia increased 26%.

These increases were largely due to population growth and aging.

Results from the GDB study were published in JAMA Oncology.

The study indicated that, in 2016, there were 17.2 million cases of cancer worldwide and 8.9 million cancer deaths.

One in 3 men were likely to get cancer during their lifetime, as were 1 in 5 women. Cancer was associated with 213.2 million disability-adjusted life years (DALYs).

The following table lists the 2016 global incidence and mortality figures for all cancers combined and for individual hematologic malignancies.

Leukemia

In 2016, there were 467,000 new cases of leukemia and 310,000 leukemia deaths. Leukemia was responsible for 10.2 million DALYs. Leukemia developed in 1 in 118 men and 1 in 194 women worldwide.

Between 2006 and 2016, the global leukemia incidence increased by 26%—from 370,482 to 466,802 cases.

The researchers said the factors contributing to this increase were population growth (12%), population aging (10%), and an increase in age-specific incidence rates (3%).

NHL

In 2016, there were 461,000 new cases of NHL and 240,000 NHL deaths. NHL was responsible for 6.8 million DALYs. NHL developed in 1 in 110 men and 1 in 161 women worldwide.

Between 2006 and 2016, NHL increased by 45%, from 319,078 to 461,164 cases.

The factors contributing to this increase were increasing age-specific incidence rates (17%), changing population age structure (15%), and population growth (12%).

“A large proportion of the increase in cancer incidence can be explained by improving life expectancy and population growth—a development that can at least partially be attributed to a reduced burden from other common diseases,” the study authors wrote.

The authors also pointed out that prevention efforts are less effective for hematologic malignancies than for other cancers.

Photo by Rhoda Baer

Research has shown an increase in the global incidence of leukemia and non-Hodgkin lymphoma (NHL) in recent years.

The Global Burden of Disease (GBD) study showed that, from 2006 to 2016, the incidence of NHL increased 45%, and the incidence of leukemia increased 26%.

These increases were largely due to population growth and aging.

Results from the GDB study were published in JAMA Oncology.

The study indicated that, in 2016, there were 17.2 million cases of cancer worldwide and 8.9 million cancer deaths.

One in 3 men were likely to get cancer during their lifetime, as were 1 in 5 women. Cancer was associated with 213.2 million disability-adjusted life years (DALYs).

The following table lists the 2016 global incidence and mortality figures for all cancers combined and for individual hematologic malignancies.

Leukemia

In 2016, there were 467,000 new cases of leukemia and 310,000 leukemia deaths. Leukemia was responsible for 10.2 million DALYs. Leukemia developed in 1 in 118 men and 1 in 194 women worldwide.

Between 2006 and 2016, the global leukemia incidence increased by 26%—from 370,482 to 466,802 cases.

The researchers said the factors contributing to this increase were population growth (12%), population aging (10%), and an increase in age-specific incidence rates (3%).

NHL

In 2016, there were 461,000 new cases of NHL and 240,000 NHL deaths. NHL was responsible for 6.8 million DALYs. NHL developed in 1 in 110 men and 1 in 161 women worldwide.

Between 2006 and 2016, NHL increased by 45%, from 319,078 to 461,164 cases.

The factors contributing to this increase were increasing age-specific incidence rates (17%), changing population age structure (15%), and population growth (12%).

“A large proportion of the increase in cancer incidence can be explained by improving life expectancy and population growth—a development that can at least partially be attributed to a reduced burden from other common diseases,” the study authors wrote.

The authors also pointed out that prevention efforts are less effective for hematologic malignancies than for other cancers.

Photo by Rhoda Baer

Research has shown an increase in the global incidence of leukemia and non-Hodgkin lymphoma (NHL) in recent years.

The Global Burden of Disease (GBD) study showed that, from 2006 to 2016, the incidence of NHL increased 45%, and the incidence of leukemia increased 26%.

These increases were largely due to population growth and aging.

Results from the GDB study were published in JAMA Oncology.

The study indicated that, in 2016, there were 17.2 million cases of cancer worldwide and 8.9 million cancer deaths.

One in 3 men were likely to get cancer during their lifetime, as were 1 in 5 women. Cancer was associated with 213.2 million disability-adjusted life years (DALYs).

The following table lists the 2016 global incidence and mortality figures for all cancers combined and for individual hematologic malignancies.

Leukemia

In 2016, there were 467,000 new cases of leukemia and 310,000 leukemia deaths. Leukemia was responsible for 10.2 million DALYs. Leukemia developed in 1 in 118 men and 1 in 194 women worldwide.

Between 2006 and 2016, the global leukemia incidence increased by 26%—from 370,482 to 466,802 cases.

The researchers said the factors contributing to this increase were population growth (12%), population aging (10%), and an increase in age-specific incidence rates (3%).

NHL

In 2016, there were 461,000 new cases of NHL and 240,000 NHL deaths. NHL was responsible for 6.8 million DALYs. NHL developed in 1 in 110 men and 1 in 161 women worldwide.

Between 2006 and 2016, NHL increased by 45%, from 319,078 to 461,164 cases.

The factors contributing to this increase were increasing age-specific incidence rates (17%), changing population age structure (15%), and population growth (12%).

“A large proportion of the increase in cancer incidence can be explained by improving life expectancy and population growth—a development that can at least partially be attributed to a reduced burden from other common diseases,” the study authors wrote.

The authors also pointed out that prevention efforts are less effective for hematologic malignancies than for other cancers.

Photo courtesy of NIH

Researchers say they have developed a frailty index that can predict overall survival (OS) in patients newly diagnosed with multiple myeloma (MM).

An increasing frailty index score was significantly associated with an increased risk of death in these patients, and frailty retained a significant association with OS even after the researchers controlled for patients’ chronological age.

“Our goal was to create a tool that could be widely applied using data sources at hand and that helps doctors provide better informed treatment recommendations for their patients,” said Tanya S. Wildes, MD, of the Washington University School of Medicine in St Louis, Missouri.

“Our results demonstrate that, for patients with multiple myeloma, chronological age alone is not a good measure for assessing overall health.”

Dr Wildes and her colleagues reported these results in JCO Clinical Cancer Informatics.

Creating the index

The researchers began this study with data from 2,692,361 patients without cancer who were older than 66 years of age. The data were collected from the Medicare Health Outcomes Survey (MHOS), which is used to annually collect self-reported symptoms, functional status, and health-related quality of life data from Medicare beneficiaries enrolled in Medicare Advantage plans.

The researchers used the MHOS data to create a deficit accumulation frailty index made up of a 25-item scale and scoring system. The index includes criteria in 5 categories for scoring frailty:

• Activities of daily living (eg, difficulty dressing or eating)
• Chronic health conditions
• Functioning (eg, difficulty walking or climbing several sets of stairs)
• General health
• Mental health.

Patients whose scores exceed a certain threshold on the scale are classified as frail.

Applying the index

The researchers applied their frailty index to 305 patients with newly diagnosed MM. Data from these patients were obtained from the Surveillance, Epidemiology, and End Results (SEER)-MHOS linked database. In this dataset, data from MHOS are linked to demographics, tumor characteristics, and survival for individuals with a cancer diagnosis who reside in the coverage area of the 14 registries participating in the SEER-MHOS linkage.

The researchers compared findings in the MM patients to findings in the patients without cancer.

In the non-cancer patients, the median age was 74, and the mean frailty score was 0.23. In the MM patients, the median age was 76, and the mean frailty score was 0.28.

Chronological age was weakly correlated with a higher frailty score in MM patients. However, for non-cancer patients, an increase in chronological age was strongly correlated with a higher frailty score.

Among non-cancer patients, each 10% increase in frailty score was associated with a 40% increased risk for death (adjusted hazard ratio, 1.397; P<0.001).

Among MM patients, each 10% increase in frailty score was associated with a 16% increased risk of death (adjusted hazard ratio, 1.159; P<0.001).

The median OS was 33 months for the entire MM cohort, 26.8 months for frail MM patients, and 43.7 months for non-frail MM patients (P=0.015 for the frail to non-frail comparison).

“These findings underscore the need to place more consideration on biological age versus chronological age in multiple myeloma, recognizing that frailty is dynamic and encompasses many factors beyond the disease itself,” Dr Wildes said.

“Ultimately, the hope is that this tool will help us to better personalize care based on a fuller picture of our patients’ health so that we are not under-treating an older adult who can tolerate a more intense therapy or over-treating one who’s going to be vulnerable to the toxicities of therapy.”

Limitations and next steps

The researchers believe there are several options for optimizing the data in the frailty index, including turning it into a computerized program and examining patients who are not newly diagnosed and have subsequent relapses, disease burden, and treatment toxicities.

This study is limited in the fact that researchers only assessed OS and not progression-free survival, chemotherapy toxicity, or hospitalization rates.

Additionally, the MM data was derived from patients enrolled in the Medicare Advantage program, which may have contributed to selecting participants who are, overall, lower-risk due to the way the program incentivizes lower-cost enrollees.

Photo courtesy of NIH

Researchers say they have developed a frailty index that can predict overall survival (OS) in patients newly diagnosed with multiple myeloma (MM).

An increasing frailty index score was significantly associated with an increased risk of death in these patients, and frailty retained a significant association with OS even after the researchers controlled for patients’ chronological age.

“Our goal was to create a tool that could be widely applied using data sources at hand and that helps doctors provide better informed treatment recommendations for their patients,” said Tanya S. Wildes, MD, of the Washington University School of Medicine in St Louis, Missouri.

“Our results demonstrate that, for patients with multiple myeloma, chronological age alone is not a good measure for assessing overall health.”

Dr Wildes and her colleagues reported these results in JCO Clinical Cancer Informatics.

Creating the index

The researchers began this study with data from 2,692,361 patients without cancer who were older than 66 years of age. The data were collected from the Medicare Health Outcomes Survey (MHOS), which is used to annually collect self-reported symptoms, functional status, and health-related quality of life data from Medicare beneficiaries enrolled in Medicare Advantage plans.

The researchers used the MHOS data to create a deficit accumulation frailty index made up of a 25-item scale and scoring system. The index includes criteria in 5 categories for scoring frailty:

• Activities of daily living (eg, difficulty dressing or eating)
• Chronic health conditions
• Functioning (eg, difficulty walking or climbing several sets of stairs)
• General health
• Mental health.

Patients whose scores exceed a certain threshold on the scale are classified as frail.

Applying the index

The researchers applied their frailty index to 305 patients with newly diagnosed MM. Data from these patients were obtained from the Surveillance, Epidemiology, and End Results (SEER)-MHOS linked database. In this dataset, data from MHOS are linked to demographics, tumor characteristics, and survival for individuals with a cancer diagnosis who reside in the coverage area of the 14 registries participating in the SEER-MHOS linkage.

The researchers compared findings in the MM patients to findings in the patients without cancer.

In the non-cancer patients, the median age was 74, and the mean frailty score was 0.23. In the MM patients, the median age was 76, and the mean frailty score was 0.28.

Chronological age was weakly correlated with a higher frailty score in MM patients. However, for non-cancer patients, an increase in chronological age was strongly correlated with a higher frailty score.

Among non-cancer patients, each 10% increase in frailty score was associated with a 40% increased risk for death (adjusted hazard ratio, 1.397; P<0.001).

Among MM patients, each 10% increase in frailty score was associated with a 16% increased risk of death (adjusted hazard ratio, 1.159; P<0.001).

The median OS was 33 months for the entire MM cohort, 26.8 months for frail MM patients, and 43.7 months for non-frail MM patients (P=0.015 for the frail to non-frail comparison).

“These findings underscore the need to place more consideration on biological age versus chronological age in multiple myeloma, recognizing that frailty is dynamic and encompasses many factors beyond the disease itself,” Dr Wildes said.

“Ultimately, the hope is that this tool will help us to better personalize care based on a fuller picture of our patients’ health so that we are not under-treating an older adult who can tolerate a more intense therapy or over-treating one who’s going to be vulnerable to the toxicities of therapy.”

Limitations and next steps

The researchers believe there are several options for optimizing the data in the frailty index, including turning it into a computerized program and examining patients who are not newly diagnosed and have subsequent relapses, disease burden, and treatment toxicities.

This study is limited in the fact that researchers only assessed OS and not progression-free survival, chemotherapy toxicity, or hospitalization rates.

Additionally, the MM data was derived from patients enrolled in the Medicare Advantage program, which may have contributed to selecting participants who are, overall, lower-risk due to the way the program incentivizes lower-cost enrollees.

Photo courtesy of NIH

Researchers say they have developed a frailty index that can predict overall survival (OS) in patients newly diagnosed with multiple myeloma (MM).

An increasing frailty index score was significantly associated with an increased risk of death in these patients, and frailty retained a significant association with OS even after the researchers controlled for patients’ chronological age.

“Our goal was to create a tool that could be widely applied using data sources at hand and that helps doctors provide better informed treatment recommendations for their patients,” said Tanya S. Wildes, MD, of the Washington University School of Medicine in St Louis, Missouri.

“Our results demonstrate that, for patients with multiple myeloma, chronological age alone is not a good measure for assessing overall health.”

Dr Wildes and her colleagues reported these results in JCO Clinical Cancer Informatics.

Creating the index

The researchers began this study with data from 2,692,361 patients without cancer who were older than 66 years of age. The data were collected from the Medicare Health Outcomes Survey (MHOS), which is used to annually collect self-reported symptoms, functional status, and health-related quality of life data from Medicare beneficiaries enrolled in Medicare Advantage plans.

The researchers used the MHOS data to create a deficit accumulation frailty index made up of a 25-item scale and scoring system. The index includes criteria in 5 categories for scoring frailty:

• Activities of daily living (eg, difficulty dressing or eating)
• Chronic health conditions
• Functioning (eg, difficulty walking or climbing several sets of stairs)
• General health
• Mental health.

Patients whose scores exceed a certain threshold on the scale are classified as frail.

Applying the index

The researchers applied their frailty index to 305 patients with newly diagnosed MM. Data from these patients were obtained from the Surveillance, Epidemiology, and End Results (SEER)-MHOS linked database. In this dataset, data from MHOS are linked to demographics, tumor characteristics, and survival for individuals with a cancer diagnosis who reside in the coverage area of the 14 registries participating in the SEER-MHOS linkage.

The researchers compared findings in the MM patients to findings in the patients without cancer.

In the non-cancer patients, the median age was 74, and the mean frailty score was 0.23. In the MM patients, the median age was 76, and the mean frailty score was 0.28.

Chronological age was weakly correlated with a higher frailty score in MM patients. However, for non-cancer patients, an increase in chronological age was strongly correlated with a higher frailty score.

Among non-cancer patients, each 10% increase in frailty score was associated with a 40% increased risk for death (adjusted hazard ratio, 1.397; P<0.001).

Among MM patients, each 10% increase in frailty score was associated with a 16% increased risk of death (adjusted hazard ratio, 1.159; P<0.001).

The median OS was 33 months for the entire MM cohort, 26.8 months for frail MM patients, and 43.7 months for non-frail MM patients (P=0.015 for the frail to non-frail comparison).

“These findings underscore the need to place more consideration on biological age versus chronological age in multiple myeloma, recognizing that frailty is dynamic and encompasses many factors beyond the disease itself,” Dr Wildes said.

“Ultimately, the hope is that this tool will help us to better personalize care based on a fuller picture of our patients’ health so that we are not under-treating an older adult who can tolerate a more intense therapy or over-treating one who’s going to be vulnerable to the toxicities of therapy.”

Limitations and next steps

The researchers believe there are several options for optimizing the data in the frailty index, including turning it into a computerized program and examining patients who are not newly diagnosed and have subsequent relapses, disease burden, and treatment toxicities.

This study is limited in the fact that researchers only assessed OS and not progression-free survival, chemotherapy toxicity, or hospitalization rates.

Additionally, the MM data was derived from patients enrolled in the Medicare Advantage program, which may have contributed to selecting participants who are, overall, lower-risk due to the way the program incentivizes lower-cost enrollees.

A new index of frailty predicts survival in older patients with multiple myeloma based on accumulation of aging-associated deficits, rather than chronological age alone, investigators report. A 16% increased risk of death was seen for each 10% increase in the deficit-accumulation frailty index (DAFI), which includes 25 variables related health, function, and activities of daily living.

There was only a weak correlation between chronological age and increase in deficits tracked by the index, in contrast to a cohort without cancer, in which age and frailty were strongly correlated, the investigators reported in JCO Clinical Cancer Informatics.

“Our results demonstrate that, for patients with multiple myeloma, chronological age alone is not a good measure for assessing overall health,” study author Tanya M. Wildes, MD, of Washington University, St. Louis, said in a news release from the American Society of Clinical Oncology.

Existing tools to assess frailty include an index proposed by the International Myeloma Working Group that looks at age plus other indexes related to comorbidities and activities of daily living, and the revised Myeloma Comorbidity Index that incorporates age with other prognostic factors.

“Although both tools provide prognostic information, chronological age automatically increases frailty without taking biologic or functional age into account,” Dr. Wildes and her coauthors wrote in their report.

By contrast, the DAFI is based on the concept of biologic age, in which the health status of an individual is measured based on the proportion of aging-associated deficits they have accumulated, according to the authors.

To create the DAFI, Dr. Wildes and her colleagues analyzed nearly 2.7 million records of noncancer patients aged 66 years or older in the SEER Medicare Health Outcomes Survey (MHOS) database. They identified 25 variables in the database representing chronic health conditions, activities of daily living, functioning, mental health, and general health.

An individual’s DAFI score was calculated as the sum of scores for each of the 25 variables as 0 for absent, 0.5 for limited, and 1 for present. Predicted DAFI means were calculated for each year of age and used to create age-specific cut points to determine whether an individual would be considered frail or not versus others of the same age.

“In other words, the same frailty score may qualify an 80-year-old individual as fit and a 70-year-old as frail, depending on the cutoff for their respective age group,” investigators explained in their report.

They applied the index to 305 patients with newly diagnosed myeloma in the SEER-MHOS database who were 66 years of age or older (median age, 76 years) and had completed the survey within 1 year of diagnosis.

The DAFI classified 52% of the myeloma patients as frail, and for that group, median overall survival was 26.8 months, versus 43.7 months for nonfrail patients (P = .015), according to the reported data. For each 10% increase in score, the risk of death increased by 16% (P less than .001).

Notably, advancing age was very weakly correlated with increased age-related deficits in the myeloma cohort (r2 = 0.15; P = .010), according to investigators, but very strongly correlated with deficits in the cohort of noncancer patients (r2 = 0.98; P less than .001).

“This suggests that, in patients with multiple myeloma, the prevalence of impairments across domains of function, chronic comorbidities, general health, and mental health are more related to the overall burden of myeloma rather than chronological age alone,” the investigators wrote.

The information used to calculate a DAFI score is easily obtainable during a clinic visit, according to the authors, who provided an overview of all 25 variables in the journal article.

Further development of a computerized program would further enhance usability in the clinic, allowing for real-time calculation during a patient visit, they said.

Survivorship expert Merry Jennifer Markham, MD, said in the ASCO news release that this frailty index is notable because it accounts for more than just chronological age. “Knowing this information can help oncologists have more informed discussions with patients about their prognosis, which in turn can empower patients and families as they weigh treatment options,” she said.

The research was supported by National Cancer Institute. Dr. Wildes reported honoraria from Carevive Systems and research funding from Janssen Oncology. Another coauthor reported honoraria from Celgene and Janssen, and a consulting or advisory role with Amgen and Takeda.

 

SOURCE: Mian HS et al. JCO Clin Cancer Inform. 2018 Jul 25. 2018 Jul 25. doi: 10.1200/CCI.18.00043.

A new index of frailty predicts survival in older patients with multiple myeloma based on accumulation of aging-associated deficits, rather than chronological age alone, investigators report. A 16% increased risk of death was seen for each 10% increase in the deficit-accumulation frailty index (DAFI), which includes 25 variables related health, function, and activities of daily living.

There was only a weak correlation between chronological age and increase in deficits tracked by the index, in contrast to a cohort without cancer, in which age and frailty were strongly correlated, the investigators reported in JCO Clinical Cancer Informatics.

“Our results demonstrate that, for patients with multiple myeloma, chronological age alone is not a good measure for assessing overall health,” study author Tanya M. Wildes, MD, of Washington University, St. Louis, said in a news release from the American Society of Clinical Oncology.

Existing tools to assess frailty include an index proposed by the International Myeloma Working Group that looks at age plus other indexes related to comorbidities and activities of daily living, and the revised Myeloma Comorbidity Index that incorporates age with other prognostic factors.

“Although both tools provide prognostic information, chronological age automatically increases frailty without taking biologic or functional age into account,” Dr. Wildes and her coauthors wrote in their report.

By contrast, the DAFI is based on the concept of biologic age, in which the health status of an individual is measured based on the proportion of aging-associated deficits they have accumulated, according to the authors.

To create the DAFI, Dr. Wildes and her colleagues analyzed nearly 2.7 million records of noncancer patients aged 66 years or older in the SEER Medicare Health Outcomes Survey (MHOS) database. They identified 25 variables in the database representing chronic health conditions, activities of daily living, functioning, mental health, and general health.

An individual’s DAFI score was calculated as the sum of scores for each of the 25 variables as 0 for absent, 0.5 for limited, and 1 for present. Predicted DAFI means were calculated for each year of age and used to create age-specific cut points to determine whether an individual would be considered frail or not versus others of the same age.

“In other words, the same frailty score may qualify an 80-year-old individual as fit and a 70-year-old as frail, depending on the cutoff for their respective age group,” investigators explained in their report.

They applied the index to 305 patients with newly diagnosed myeloma in the SEER-MHOS database who were 66 years of age or older (median age, 76 years) and had completed the survey within 1 year of diagnosis.

The DAFI classified 52% of the myeloma patients as frail, and for that group, median overall survival was 26.8 months, versus 43.7 months for nonfrail patients (P = .015), according to the reported data. For each 10% increase in score, the risk of death increased by 16% (P less than .001).

Notably, advancing age was very weakly correlated with increased age-related deficits in the myeloma cohort (r2 = 0.15; P = .010), according to investigators, but very strongly correlated with deficits in the cohort of noncancer patients (r2 = 0.98; P less than .001).

“This suggests that, in patients with multiple myeloma, the prevalence of impairments across domains of function, chronic comorbidities, general health, and mental health are more related to the overall burden of myeloma rather than chronological age alone,” the investigators wrote.

The information used to calculate a DAFI score is easily obtainable during a clinic visit, according to the authors, who provided an overview of all 25 variables in the journal article.

Further development of a computerized program would further enhance usability in the clinic, allowing for real-time calculation during a patient visit, they said.

Survivorship expert Merry Jennifer Markham, MD, said in the ASCO news release that this frailty index is notable because it accounts for more than just chronological age. “Knowing this information can help oncologists have more informed discussions with patients about their prognosis, which in turn can empower patients and families as they weigh treatment options,” she said.

The research was supported by National Cancer Institute. Dr. Wildes reported honoraria from Carevive Systems and research funding from Janssen Oncology. Another coauthor reported honoraria from Celgene and Janssen, and a consulting or advisory role with Amgen and Takeda.

 

SOURCE: Mian HS et al. JCO Clin Cancer Inform. 2018 Jul 25. 2018 Jul 25. doi: 10.1200/CCI.18.00043.

A new index of frailty predicts survival in older patients with multiple myeloma based on accumulation of aging-associated deficits, rather than chronological age alone, investigators report. A 16% increased risk of death was seen for each 10% increase in the deficit-accumulation frailty index (DAFI), which includes 25 variables related health, function, and activities of daily living.

There was only a weak correlation between chronological age and increase in deficits tracked by the index, in contrast to a cohort without cancer, in which age and frailty were strongly correlated, the investigators reported in JCO Clinical Cancer Informatics.

“Our results demonstrate that, for patients with multiple myeloma, chronological age alone is not a good measure for assessing overall health,” study author Tanya M. Wildes, MD, of Washington University, St. Louis, said in a news release from the American Society of Clinical Oncology.

Existing tools to assess frailty include an index proposed by the International Myeloma Working Group that looks at age plus other indexes related to comorbidities and activities of daily living, and the revised Myeloma Comorbidity Index that incorporates age with other prognostic factors.

“Although both tools provide prognostic information, chronological age automatically increases frailty without taking biologic or functional age into account,” Dr. Wildes and her coauthors wrote in their report.

By contrast, the DAFI is based on the concept of biologic age, in which the health status of an individual is measured based on the proportion of aging-associated deficits they have accumulated, according to the authors.

To create the DAFI, Dr. Wildes and her colleagues analyzed nearly 2.7 million records of noncancer patients aged 66 years or older in the SEER Medicare Health Outcomes Survey (MHOS) database. They identified 25 variables in the database representing chronic health conditions, activities of daily living, functioning, mental health, and general health.

An individual’s DAFI score was calculated as the sum of scores for each of the 25 variables as 0 for absent, 0.5 for limited, and 1 for present. Predicted DAFI means were calculated for each year of age and used to create age-specific cut points to determine whether an individual would be considered frail or not versus others of the same age.

“In other words, the same frailty score may qualify an 80-year-old individual as fit and a 70-year-old as frail, depending on the cutoff for their respective age group,” investigators explained in their report.

They applied the index to 305 patients with newly diagnosed myeloma in the SEER-MHOS database who were 66 years of age or older (median age, 76 years) and had completed the survey within 1 year of diagnosis.

The DAFI classified 52% of the myeloma patients as frail, and for that group, median overall survival was 26.8 months, versus 43.7 months for nonfrail patients (P = .015), according to the reported data. For each 10% increase in score, the risk of death increased by 16% (P less than .001).

Notably, advancing age was very weakly correlated with increased age-related deficits in the myeloma cohort (r2 = 0.15; P = .010), according to investigators, but very strongly correlated with deficits in the cohort of noncancer patients (r2 = 0.98; P less than .001).

“This suggests that, in patients with multiple myeloma, the prevalence of impairments across domains of function, chronic comorbidities, general health, and mental health are more related to the overall burden of myeloma rather than chronological age alone,” the investigators wrote.

The information used to calculate a DAFI score is easily obtainable during a clinic visit, according to the authors, who provided an overview of all 25 variables in the journal article.

Further development of a computerized program would further enhance usability in the clinic, allowing for real-time calculation during a patient visit, they said.

Survivorship expert Merry Jennifer Markham, MD, said in the ASCO news release that this frailty index is notable because it accounts for more than just chronological age. “Knowing this information can help oncologists have more informed discussions with patients about their prognosis, which in turn can empower patients and families as they weigh treatment options,” she said.

The research was supported by National Cancer Institute. Dr. Wildes reported honoraria from Carevive Systems and research funding from Janssen Oncology. Another coauthor reported honoraria from Celgene and Janssen, and a consulting or advisory role with Amgen and Takeda.

 

SOURCE: Mian HS et al. JCO Clin Cancer Inform. 2018 Jul 25. 2018 Jul 25. doi: 10.1200/CCI.18.00043.

showing multiple myeloma

The US Food and Drug Administration (FDA) has granted fast track designation to the cancer vaccine galinpepimut-S (GPS) for the treatment of multiple myeloma (MM).

GPS consists of 4 modified peptide chains that induce an innate immune response (CD4+/CD8+ T cells) against the Wilms’ tumor 1 (WT1) antigen.

GPS is administered in combination with an adjuvant and an immune modulator to improve the immune response to the target.

GPS has been tested in a phase 2 trial of patients with MM. Results from this trial were presented at the 44th Annual Meeting of the EBMT in March.

Phase 2 trial

The study enrolled 19 MM patients. Fifteen of them had high-risk cytogenetics at diagnosis, and 18 were at least minimal residual disease-positive after autologous stem cell transplant (ASCT).

Patients began receiving GPS within 22 days of ASCT. Initially, they received 6 doses (administered subcutaneously with the oil emulsifier montanide) every 2 weeks. Injection sites were pre-stimulated with granulocyte-macrophage colony-stimulating factor (70 μg) on days -2 (± 1 day) and 0 of each GPS vaccination.

The patients underwent assessment 2 to 4 weeks after the 6th GPS dose. Then, they received 6 additional monthly doses of GPS in conjunction with lenalidomide maintenance (10 mg daily), starting on day 100 post-ASCT. Patients were assessed 2 to 4 weeks after the 12th GPS dose.

The researchers found that GPS stimulated time-dependent CD4+ or CD8+ T-cell immune responses specific for all 4 WT1 peptides within GPS, 2 of which are heteroclitic.

Immune responses were confirmed in up to 91% of patients, with multivalent immune responses in up to 64% of patients. Three-quarters of patients had multifunctional cross-epitope T-cell reactivity to antigenic epitopes against which the hosts were not specifically immunized, in a pattern akin to epitope spreading.

In patients who received all 12 doses of GPS (n=12), there was a “strong” association between clinical benefit—defined as complete response (CR) or very good partial response (VGPR)—and frequency of CD4/CD8 immune responses.

Of those patients who had achieved CR/VGPR upon completion of GPS treatment, 100% (n=11) had CD4 immune responses, and 81.8% (n=9) had CD8 immune responses.

The median progression-free survival was 23.6 months, and the median overall survival was not reached. At 18 months, the rate of progression-free survival was 62%, and the rate of overall survival was 88%.

About fast track designation

The FDA’s fast track development program is designed to expedite clinical development and submission of applications for products with the potential to treat serious or life-threatening conditions and address unmet medical needs.

Fast track designation facilitates frequent interactions with the FDA review team, including meetings to discuss the product’s development plan and written communications about issues such as trial design and use of biomarkers.

Products that receive fast track designation may be eligible for accelerated approval and priority review if relevant criteria are met. Such products may also be eligible for rolling review, which allows a developer to submit individual sections of a product’s application for review as they are ready, rather than waiting until all sections are complete.

showing multiple myeloma

The US Food and Drug Administration (FDA) has granted fast track designation to the cancer vaccine galinpepimut-S (GPS) for the treatment of multiple myeloma (MM).

GPS consists of 4 modified peptide chains that induce an innate immune response (CD4+/CD8+ T cells) against the Wilms’ tumor 1 (WT1) antigen.

GPS is administered in combination with an adjuvant and an immune modulator to improve the immune response to the target.

GPS has been tested in a phase 2 trial of patients with MM. Results from this trial were presented at the 44th Annual Meeting of the EBMT in March.

Phase 2 trial

The study enrolled 19 MM patients. Fifteen of them had high-risk cytogenetics at diagnosis, and 18 were at least minimal residual disease-positive after autologous stem cell transplant (ASCT).

Patients began receiving GPS within 22 days of ASCT. Initially, they received 6 doses (administered subcutaneously with the oil emulsifier montanide) every 2 weeks. Injection sites were pre-stimulated with granulocyte-macrophage colony-stimulating factor (70 μg) on days -2 (± 1 day) and 0 of each GPS vaccination.

The patients underwent assessment 2 to 4 weeks after the 6th GPS dose. Then, they received 6 additional monthly doses of GPS in conjunction with lenalidomide maintenance (10 mg daily), starting on day 100 post-ASCT. Patients were assessed 2 to 4 weeks after the 12th GPS dose.

The researchers found that GPS stimulated time-dependent CD4+ or CD8+ T-cell immune responses specific for all 4 WT1 peptides within GPS, 2 of which are heteroclitic.

Immune responses were confirmed in up to 91% of patients, with multivalent immune responses in up to 64% of patients. Three-quarters of patients had multifunctional cross-epitope T-cell reactivity to antigenic epitopes against which the hosts were not specifically immunized, in a pattern akin to epitope spreading.

In patients who received all 12 doses of GPS (n=12), there was a “strong” association between clinical benefit—defined as complete response (CR) or very good partial response (VGPR)—and frequency of CD4/CD8 immune responses.

Of those patients who had achieved CR/VGPR upon completion of GPS treatment, 100% (n=11) had CD4 immune responses, and 81.8% (n=9) had CD8 immune responses.

The median progression-free survival was 23.6 months, and the median overall survival was not reached. At 18 months, the rate of progression-free survival was 62%, and the rate of overall survival was 88%.

About fast track designation

The FDA’s fast track development program is designed to expedite clinical development and submission of applications for products with the potential to treat serious or life-threatening conditions and address unmet medical needs.

Fast track designation facilitates frequent interactions with the FDA review team, including meetings to discuss the product’s development plan and written communications about issues such as trial design and use of biomarkers.

Products that receive fast track designation may be eligible for accelerated approval and priority review if relevant criteria are met. Such products may also be eligible for rolling review, which allows a developer to submit individual sections of a product’s application for review as they are ready, rather than waiting until all sections are complete.

showing multiple myeloma

The US Food and Drug Administration (FDA) has granted fast track designation to the cancer vaccine galinpepimut-S (GPS) for the treatment of multiple myeloma (MM).

GPS consists of 4 modified peptide chains that induce an innate immune response (CD4+/CD8+ T cells) against the Wilms’ tumor 1 (WT1) antigen.

GPS is administered in combination with an adjuvant and an immune modulator to improve the immune response to the target.

GPS has been tested in a phase 2 trial of patients with MM. Results from this trial were presented at the 44th Annual Meeting of the EBMT in March.

Phase 2 trial

The study enrolled 19 MM patients. Fifteen of them had high-risk cytogenetics at diagnosis, and 18 were at least minimal residual disease-positive after autologous stem cell transplant (ASCT).

Patients began receiving GPS within 22 days of ASCT. Initially, they received 6 doses (administered subcutaneously with the oil emulsifier montanide) every 2 weeks. Injection sites were pre-stimulated with granulocyte-macrophage colony-stimulating factor (70 μg) on days -2 (± 1 day) and 0 of each GPS vaccination.

The patients underwent assessment 2 to 4 weeks after the 6th GPS dose. Then, they received 6 additional monthly doses of GPS in conjunction with lenalidomide maintenance (10 mg daily), starting on day 100 post-ASCT. Patients were assessed 2 to 4 weeks after the 12th GPS dose.

The researchers found that GPS stimulated time-dependent CD4+ or CD8+ T-cell immune responses specific for all 4 WT1 peptides within GPS, 2 of which are heteroclitic.

Immune responses were confirmed in up to 91% of patients, with multivalent immune responses in up to 64% of patients. Three-quarters of patients had multifunctional cross-epitope T-cell reactivity to antigenic epitopes against which the hosts were not specifically immunized, in a pattern akin to epitope spreading.

In patients who received all 12 doses of GPS (n=12), there was a “strong” association between clinical benefit—defined as complete response (CR) or very good partial response (VGPR)—and frequency of CD4/CD8 immune responses.

Of those patients who had achieved CR/VGPR upon completion of GPS treatment, 100% (n=11) had CD4 immune responses, and 81.8% (n=9) had CD8 immune responses.

The median progression-free survival was 23.6 months, and the median overall survival was not reached. At 18 months, the rate of progression-free survival was 62%, and the rate of overall survival was 88%.

About fast track designation

The FDA’s fast track development program is designed to expedite clinical development and submission of applications for products with the potential to treat serious or life-threatening conditions and address unmet medical needs.

Fast track designation facilitates frequent interactions with the FDA review team, including meetings to discuss the product’s development plan and written communications about issues such as trial design and use of biomarkers.

Products that receive fast track designation may be eligible for accelerated approval and priority review if relevant criteria are met. Such products may also be eligible for rolling review, which allows a developer to submit individual sections of a product’s application for review as they are ready, rather than waiting until all sections are complete.

Photo by Bill Branson

The US Food and Drug Administration (FDA) has approved the leukocyte growth factor Nivestym™ (filgrastim-aafi), a biosimilar to Neupogen (filgrastim).

Nivestym is approved to treat patients with nonmyeloid malignancies who are receiving myelosuppressive chemotherapy or undergoing bone marrow transplant, acute myeloid leukemia patients receiving induction or consolidation chemotherapy, patients undergoing autologous peripheral blood progenitor cell collection, and patients with severe chronic neutropenia.

The FDA’s approval of Nivestym was based on a review of evidence suggesting the drug is highly similar to Neupogen, according to Pfizer, the company developing Nivestym.

The full approved indication for Nivestym is as follows:

• To decrease the incidence of infection, as manifested by febrile neutropenia, in patients with nonmyeloid malignancies receiving myelosuppressive anticancer drugs associated with a significant incidence of severe neutropenia with fever
• To reduce the time to neutrophil recovery and the duration of fever following induction or consolidation chemotherapy in patients with acute myeloid leukemia
• To reduce the duration of neutropenia and neutropenia-related clinical sequelae (eg, febrile neutropenia) in patients with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by bone marrow transplant
• For the mobilization of autologous hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis
• For chronic administration to reduce the incidence and duration of sequelae of severe neutropenia (eg, fever, infections, oropharyngeal ulcers) in symptomatic patients with congenital neutropenia, cyclic neutropenia, or idiopathic neutropenia.

For more details on Nivestym, see the full prescribing information.

Photo by Bill Branson

The US Food and Drug Administration (FDA) has approved the leukocyte growth factor Nivestym™ (filgrastim-aafi), a biosimilar to Neupogen (filgrastim).

Nivestym is approved to treat patients with nonmyeloid malignancies who are receiving myelosuppressive chemotherapy or undergoing bone marrow transplant, acute myeloid leukemia patients receiving induction or consolidation chemotherapy, patients undergoing autologous peripheral blood progenitor cell collection, and patients with severe chronic neutropenia.

The FDA’s approval of Nivestym was based on a review of evidence suggesting the drug is highly similar to Neupogen, according to Pfizer, the company developing Nivestym.

The full approved indication for Nivestym is as follows:

• To decrease the incidence of infection, as manifested by febrile neutropenia, in patients with nonmyeloid malignancies receiving myelosuppressive anticancer drugs associated with a significant incidence of severe neutropenia with fever
• To reduce the time to neutrophil recovery and the duration of fever following induction or consolidation chemotherapy in patients with acute myeloid leukemia
• To reduce the duration of neutropenia and neutropenia-related clinical sequelae (eg, febrile neutropenia) in patients with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by bone marrow transplant
• For the mobilization of autologous hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis
• For chronic administration to reduce the incidence and duration of sequelae of severe neutropenia (eg, fever, infections, oropharyngeal ulcers) in symptomatic patients with congenital neutropenia, cyclic neutropenia, or idiopathic neutropenia.

For more details on Nivestym, see the full prescribing information.

Photo by Bill Branson

The US Food and Drug Administration (FDA) has approved the leukocyte growth factor Nivestym™ (filgrastim-aafi), a biosimilar to Neupogen (filgrastim).

Nivestym is approved to treat patients with nonmyeloid malignancies who are receiving myelosuppressive chemotherapy or undergoing bone marrow transplant, acute myeloid leukemia patients receiving induction or consolidation chemotherapy, patients undergoing autologous peripheral blood progenitor cell collection, and patients with severe chronic neutropenia.

The FDA’s approval of Nivestym was based on a review of evidence suggesting the drug is highly similar to Neupogen, according to Pfizer, the company developing Nivestym.

The full approved indication for Nivestym is as follows:

• To decrease the incidence of infection, as manifested by febrile neutropenia, in patients with nonmyeloid malignancies receiving myelosuppressive anticancer drugs associated with a significant incidence of severe neutropenia with fever
• To reduce the time to neutrophil recovery and the duration of fever following induction or consolidation chemotherapy in patients with acute myeloid leukemia
• To reduce the duration of neutropenia and neutropenia-related clinical sequelae (eg, febrile neutropenia) in patients with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by bone marrow transplant
• For the mobilization of autologous hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis
• For chronic administration to reduce the incidence and duration of sequelae of severe neutropenia (eg, fever, infections, oropharyngeal ulcers) in symptomatic patients with congenital neutropenia, cyclic neutropenia, or idiopathic neutropenia.

For more details on Nivestym, see the full prescribing information.