Multiple Myeloma

Image by Spencer Phillips

A comprehensive RNA and DNA sequencing platform can guide treatment decisions for late-stage and drug-resistant multiple myeloma (MM), according to a study published in JCO Precision Oncology.

Researchers used the platform to generate treatment suggestions for 64 MM patients who had exhausted all approved treatment options.

Of the 21 evaluable patients who received the sequencing-recommended therapies, 67% achieved a response. Five patients had ongoing responses at the end of the trial.

“Our study shows how a precision medicine approach incorporating RNA sequencing may identify viable and effective therapeutic options beyond the current FDA-approved armamentarium for multiple myeloma patients,” said study author Samir Parekh, MD, of the Icahn School of Medicine at Mount Sinai in New York, New York.

“The trial has allowed us to test the accuracy of our platform, laying the foundation for our next-generation precision medicine framework.”

Dr Parekh and his colleagues used DNA and RNA sequencing data to generate personalized treatment recommendations for 64 heavily pretreated MM patients.

The patients had received a median of 7 lines of therapy. Most patients (61%) were male, their median age was 59 (range, 40-85), and 67% had high-risk cytogenetics.

The sequencing data yielded treatment recommendations for 63 patients. Twenty-six patients (42%) actually received at least 1 of the recommended treatments.

The treatments (given alone or in combination) were:

• Trametinib (n=16)—recommended because of mutations in NRAS or KRAS
• Venetoclax (n=8)—recommended because of high BCL2 expression
• Panobinostat (n=6)—recommended due to activation of the HDAC pathway and/or by RNA-based drug repurposing selecting the pan-HDAC inhibitor vorinostat
• Dabrafenib (n=1)—recommended because of concurrent BRAF and RAS mutations
• Etoposide (n=2)—selected by RNA-based drug repurposing.

Twenty-one patients were evaluable for response. The researchers noted that 11 of these patients received treatment based on RNA findings, 8 based on DNA, and 2 based on both.

One patient achieved a complete response, 3 had a very good partial response, 10 had a partial response, 2 had a minimal response (25% reduction of disease marker), 3 had stable disease, and 2 progressed.

That means the overall response rate was 66.6% (14/21), and the clinical benefit rate (minimal response or better) was 76.2% (16/21).

The median duration of response was 131 days (range, 37-372), and 5 patients were still in response at the end of the study (September, 1, 2017).

Mount Sinai researchers have received funding to develop a clinical trial that will incorporate machine learning algorithms into this precision medicine platform, which will implement interactive learning techniques to refine the predictions based on a patient’s success with the therapies and a physician’s opinion of the treatment plan.

“This research is part of an accelerating paradigm shift in cancer therapy where treatment may be given based on the specific genomic alterations observed in a patient’s tumor rather than on the tumor histology or tissue type,” said study author Joel Dudley, PhD, of the Icahn School of Medicine at Mount Sinai.

“RNA sequencing will likely complement current precision medicine strategies in the near future due to its ability to capture more dynamic aspects of unique tumor biology and provide information beyond what is capable with DNA alone.”

Image by Spencer Phillips

A comprehensive RNA and DNA sequencing platform can guide treatment decisions for late-stage and drug-resistant multiple myeloma (MM), according to a study published in JCO Precision Oncology.

Researchers used the platform to generate treatment suggestions for 64 MM patients who had exhausted all approved treatment options.

Of the 21 evaluable patients who received the sequencing-recommended therapies, 67% achieved a response. Five patients had ongoing responses at the end of the trial.

“Our study shows how a precision medicine approach incorporating RNA sequencing may identify viable and effective therapeutic options beyond the current FDA-approved armamentarium for multiple myeloma patients,” said study author Samir Parekh, MD, of the Icahn School of Medicine at Mount Sinai in New York, New York.

“The trial has allowed us to test the accuracy of our platform, laying the foundation for our next-generation precision medicine framework.”

Dr Parekh and his colleagues used DNA and RNA sequencing data to generate personalized treatment recommendations for 64 heavily pretreated MM patients.

The patients had received a median of 7 lines of therapy. Most patients (61%) were male, their median age was 59 (range, 40-85), and 67% had high-risk cytogenetics.

The sequencing data yielded treatment recommendations for 63 patients. Twenty-six patients (42%) actually received at least 1 of the recommended treatments.

The treatments (given alone or in combination) were:

• Trametinib (n=16)—recommended because of mutations in NRAS or KRAS
• Venetoclax (n=8)—recommended because of high BCL2 expression
• Panobinostat (n=6)—recommended due to activation of the HDAC pathway and/or by RNA-based drug repurposing selecting the pan-HDAC inhibitor vorinostat
• Dabrafenib (n=1)—recommended because of concurrent BRAF and RAS mutations
• Etoposide (n=2)—selected by RNA-based drug repurposing.

Twenty-one patients were evaluable for response. The researchers noted that 11 of these patients received treatment based on RNA findings, 8 based on DNA, and 2 based on both.

One patient achieved a complete response, 3 had a very good partial response, 10 had a partial response, 2 had a minimal response (25% reduction of disease marker), 3 had stable disease, and 2 progressed.

That means the overall response rate was 66.6% (14/21), and the clinical benefit rate (minimal response or better) was 76.2% (16/21).

The median duration of response was 131 days (range, 37-372), and 5 patients were still in response at the end of the study (September, 1, 2017).

Mount Sinai researchers have received funding to develop a clinical trial that will incorporate machine learning algorithms into this precision medicine platform, which will implement interactive learning techniques to refine the predictions based on a patient’s success with the therapies and a physician’s opinion of the treatment plan.

“This research is part of an accelerating paradigm shift in cancer therapy where treatment may be given based on the specific genomic alterations observed in a patient’s tumor rather than on the tumor histology or tissue type,” said study author Joel Dudley, PhD, of the Icahn School of Medicine at Mount Sinai.

“RNA sequencing will likely complement current precision medicine strategies in the near future due to its ability to capture more dynamic aspects of unique tumor biology and provide information beyond what is capable with DNA alone.”

Image by Spencer Phillips

A comprehensive RNA and DNA sequencing platform can guide treatment decisions for late-stage and drug-resistant multiple myeloma (MM), according to a study published in JCO Precision Oncology.

Researchers used the platform to generate treatment suggestions for 64 MM patients who had exhausted all approved treatment options.

Of the 21 evaluable patients who received the sequencing-recommended therapies, 67% achieved a response. Five patients had ongoing responses at the end of the trial.

“Our study shows how a precision medicine approach incorporating RNA sequencing may identify viable and effective therapeutic options beyond the current FDA-approved armamentarium for multiple myeloma patients,” said study author Samir Parekh, MD, of the Icahn School of Medicine at Mount Sinai in New York, New York.

“The trial has allowed us to test the accuracy of our platform, laying the foundation for our next-generation precision medicine framework.”

Dr Parekh and his colleagues used DNA and RNA sequencing data to generate personalized treatment recommendations for 64 heavily pretreated MM patients.

The patients had received a median of 7 lines of therapy. Most patients (61%) were male, their median age was 59 (range, 40-85), and 67% had high-risk cytogenetics.

The sequencing data yielded treatment recommendations for 63 patients. Twenty-six patients (42%) actually received at least 1 of the recommended treatments.

The treatments (given alone or in combination) were:

• Trametinib (n=16)—recommended because of mutations in NRAS or KRAS
• Venetoclax (n=8)—recommended because of high BCL2 expression
• Panobinostat (n=6)—recommended due to activation of the HDAC pathway and/or by RNA-based drug repurposing selecting the pan-HDAC inhibitor vorinostat
• Dabrafenib (n=1)—recommended because of concurrent BRAF and RAS mutations
• Etoposide (n=2)—selected by RNA-based drug repurposing.

Twenty-one patients were evaluable for response. The researchers noted that 11 of these patients received treatment based on RNA findings, 8 based on DNA, and 2 based on both.

One patient achieved a complete response, 3 had a very good partial response, 10 had a partial response, 2 had a minimal response (25% reduction of disease marker), 3 had stable disease, and 2 progressed.

That means the overall response rate was 66.6% (14/21), and the clinical benefit rate (minimal response or better) was 76.2% (16/21).

The median duration of response was 131 days (range, 37-372), and 5 patients were still in response at the end of the study (September, 1, 2017).

Mount Sinai researchers have received funding to develop a clinical trial that will incorporate machine learning algorithms into this precision medicine platform, which will implement interactive learning techniques to refine the predictions based on a patient’s success with the therapies and a physician’s opinion of the treatment plan.

“This research is part of an accelerating paradigm shift in cancer therapy where treatment may be given based on the specific genomic alterations observed in a patient’s tumor rather than on the tumor histology or tissue type,” said study author Joel Dudley, PhD, of the Icahn School of Medicine at Mount Sinai.

“RNA sequencing will likely complement current precision medicine strategies in the near future due to its ability to capture more dynamic aspects of unique tumor biology and provide information beyond what is capable with DNA alone.”

multiple myeloma

Researchers say they have developed a computational platform that can be used to identify optimal treatments for multiple myeloma (MM).

Using this tool, the quadratic phenotypic optimization platform (QPOP), the researchers identified a 2-drug combination that proved effective against bortezomib-resistant MM in vitro.

The combination—decitabine and mitomycin C—also decreased tumor volume and prolonged survival in a mouse model of bortezomib-resistant MM.

Masturah Bte Mohd Abdul Rashid, of the Cancer Science Institute of Singapore, and her colleagues reported these results in Science Translational Medicine.

The researchers explained that QPOP approximates biological responses to therapies using advanced mathematical equations. Unlike conventional models, QPOP doesn’t require predetermined information about the mechanisms or composition of a drug.

To test QPOP’s utility in MM, the researchers began by identifying candidate drugs that might be effective against bortezomib-resistant MM. They screened 114 approved oncology drugs on 2 MM cell lines—RPMI 8226 and bortezomib-resistant RPMI 8226 (P100v).

The drugs that proved most effective against P100v were dactinomycin, decitabine, mechlorethamine hydrochloride, and mitomycin C.

The researchers wanted to identify optimal drug combinations, so they conducted a QPOP analysis including the 4 most effective drugs and an additional 10 drugs used to treat MM. The 10 drugs were bortezomib, carfilzomib, cyclophosphamide monohydrate, dexamethasone, doxorubucin, lenalidomide, panobinostat, plerixafor, thalidomide, and zoledronic acid.

The team tested 2 dosages of the 14 drugs in 128 combinations, then narrowed the list to 9 drugs and tested them at 3 dosages in 155 combinations.

This revealed the top 3 combinations:

• Decitabine and mitomycin C
• Mechlorethamine hydrochloride, decitabine, and mitomycin C
• Bortezomib, mechlorethamine hydrochloride, and mitomycin C.

The researchers said these combinations act by reversing the DNA methylation and tumor suppressor silencing that often occurs after acquired bortezomib resistance.

The team noted that the top 3 combinations had synergistic interactions, but the QPOP analysis revealed antagonistic interactions as well. For example, bortezomib and dexamethasone proved antagonistic, as did bortezomib and panobinostat.

The researchers conducted further testing to determine the optimal dosage of decitabine and mitomycin C. Results suggested both drugs should be given at 1.5 mg/kg.

The team then treated P100v tumor-bearing mice with decitabine and mitomycin C, both at 1.5 mg/kg, either alone or in combination.

Mice that received the combination had a decrease in tumor size and prolonged survival compared to mice that received DMSO (P=0.0130), decitabine alone (P=0.0121), or mitomycin C alone (P=0.00174).

The researchers also compared decitabine and mitomycin C in combination to 2 bortezomib-based combinations used to treat MM—bortezomib/dexamethasone/melphalan and bortezomib/dexamethasone/lenalidomide—in P100v tumor-bearing mice.

There was a significant decrease in tumor volume with decitabine/mitomycin C compared to bortezomib/dexamethasone/melphalan (P=0.000376) and bortezomib/dexamethasone/lenalidomide (P=0.000691).

Mice that received decitabine/mitomycin C had significantly longer survival than mice that received bortezomib/dexamethasone/melphalan (P=0.0389) or bortezomib/dexamethasone/lenalidomide (P=0.0246).

Neither survival times nor tumor volumes were significantly different between the mice that received DMSO and those that received either of the bortezomib-based combinations.

multiple myeloma

Researchers say they have developed a computational platform that can be used to identify optimal treatments for multiple myeloma (MM).

Using this tool, the quadratic phenotypic optimization platform (QPOP), the researchers identified a 2-drug combination that proved effective against bortezomib-resistant MM in vitro.

The combination—decitabine and mitomycin C—also decreased tumor volume and prolonged survival in a mouse model of bortezomib-resistant MM.

Masturah Bte Mohd Abdul Rashid, of the Cancer Science Institute of Singapore, and her colleagues reported these results in Science Translational Medicine.

The researchers explained that QPOP approximates biological responses to therapies using advanced mathematical equations. Unlike conventional models, QPOP doesn’t require predetermined information about the mechanisms or composition of a drug.

To test QPOP’s utility in MM, the researchers began by identifying candidate drugs that might be effective against bortezomib-resistant MM. They screened 114 approved oncology drugs on 2 MM cell lines—RPMI 8226 and bortezomib-resistant RPMI 8226 (P100v).

The drugs that proved most effective against P100v were dactinomycin, decitabine, mechlorethamine hydrochloride, and mitomycin C.

The researchers wanted to identify optimal drug combinations, so they conducted a QPOP analysis including the 4 most effective drugs and an additional 10 drugs used to treat MM. The 10 drugs were bortezomib, carfilzomib, cyclophosphamide monohydrate, dexamethasone, doxorubucin, lenalidomide, panobinostat, plerixafor, thalidomide, and zoledronic acid.

The team tested 2 dosages of the 14 drugs in 128 combinations, then narrowed the list to 9 drugs and tested them at 3 dosages in 155 combinations.

This revealed the top 3 combinations:

• Decitabine and mitomycin C
• Mechlorethamine hydrochloride, decitabine, and mitomycin C
• Bortezomib, mechlorethamine hydrochloride, and mitomycin C.

The researchers said these combinations act by reversing the DNA methylation and tumor suppressor silencing that often occurs after acquired bortezomib resistance.

The team noted that the top 3 combinations had synergistic interactions, but the QPOP analysis revealed antagonistic interactions as well. For example, bortezomib and dexamethasone proved antagonistic, as did bortezomib and panobinostat.

The researchers conducted further testing to determine the optimal dosage of decitabine and mitomycin C. Results suggested both drugs should be given at 1.5 mg/kg.

The team then treated P100v tumor-bearing mice with decitabine and mitomycin C, both at 1.5 mg/kg, either alone or in combination.

Mice that received the combination had a decrease in tumor size and prolonged survival compared to mice that received DMSO (P=0.0130), decitabine alone (P=0.0121), or mitomycin C alone (P=0.00174).

The researchers also compared decitabine and mitomycin C in combination to 2 bortezomib-based combinations used to treat MM—bortezomib/dexamethasone/melphalan and bortezomib/dexamethasone/lenalidomide—in P100v tumor-bearing mice.

There was a significant decrease in tumor volume with decitabine/mitomycin C compared to bortezomib/dexamethasone/melphalan (P=0.000376) and bortezomib/dexamethasone/lenalidomide (P=0.000691).

Mice that received decitabine/mitomycin C had significantly longer survival than mice that received bortezomib/dexamethasone/melphalan (P=0.0389) or bortezomib/dexamethasone/lenalidomide (P=0.0246).

Neither survival times nor tumor volumes were significantly different between the mice that received DMSO and those that received either of the bortezomib-based combinations.

multiple myeloma

Researchers say they have developed a computational platform that can be used to identify optimal treatments for multiple myeloma (MM).

Using this tool, the quadratic phenotypic optimization platform (QPOP), the researchers identified a 2-drug combination that proved effective against bortezomib-resistant MM in vitro.

The combination—decitabine and mitomycin C—also decreased tumor volume and prolonged survival in a mouse model of bortezomib-resistant MM.

Masturah Bte Mohd Abdul Rashid, of the Cancer Science Institute of Singapore, and her colleagues reported these results in Science Translational Medicine.

The researchers explained that QPOP approximates biological responses to therapies using advanced mathematical equations. Unlike conventional models, QPOP doesn’t require predetermined information about the mechanisms or composition of a drug.

To test QPOP’s utility in MM, the researchers began by identifying candidate drugs that might be effective against bortezomib-resistant MM. They screened 114 approved oncology drugs on 2 MM cell lines—RPMI 8226 and bortezomib-resistant RPMI 8226 (P100v).

The drugs that proved most effective against P100v were dactinomycin, decitabine, mechlorethamine hydrochloride, and mitomycin C.

The researchers wanted to identify optimal drug combinations, so they conducted a QPOP analysis including the 4 most effective drugs and an additional 10 drugs used to treat MM. The 10 drugs were bortezomib, carfilzomib, cyclophosphamide monohydrate, dexamethasone, doxorubucin, lenalidomide, panobinostat, plerixafor, thalidomide, and zoledronic acid.

The team tested 2 dosages of the 14 drugs in 128 combinations, then narrowed the list to 9 drugs and tested them at 3 dosages in 155 combinations.

This revealed the top 3 combinations:

• Decitabine and mitomycin C
• Mechlorethamine hydrochloride, decitabine, and mitomycin C
• Bortezomib, mechlorethamine hydrochloride, and mitomycin C.

The researchers said these combinations act by reversing the DNA methylation and tumor suppressor silencing that often occurs after acquired bortezomib resistance.

The team noted that the top 3 combinations had synergistic interactions, but the QPOP analysis revealed antagonistic interactions as well. For example, bortezomib and dexamethasone proved antagonistic, as did bortezomib and panobinostat.

The researchers conducted further testing to determine the optimal dosage of decitabine and mitomycin C. Results suggested both drugs should be given at 1.5 mg/kg.

The team then treated P100v tumor-bearing mice with decitabine and mitomycin C, both at 1.5 mg/kg, either alone or in combination.

Mice that received the combination had a decrease in tumor size and prolonged survival compared to mice that received DMSO (P=0.0130), decitabine alone (P=0.0121), or mitomycin C alone (P=0.00174).

The researchers also compared decitabine and mitomycin C in combination to 2 bortezomib-based combinations used to treat MM—bortezomib/dexamethasone/melphalan and bortezomib/dexamethasone/lenalidomide—in P100v tumor-bearing mice.

There was a significant decrease in tumor volume with decitabine/mitomycin C compared to bortezomib/dexamethasone/melphalan (P=0.000376) and bortezomib/dexamethasone/lenalidomide (P=0.000691).

Mice that received decitabine/mitomycin C had significantly longer survival than mice that received bortezomib/dexamethasone/melphalan (P=0.0389) or bortezomib/dexamethasone/lenalidomide (P=0.0246).

Neither survival times nor tumor volumes were significantly different between the mice that received DMSO and those that received either of the bortezomib-based combinations.

Micrograph showing MM

MorphoSys AG has decided to stop developing MOR202 as a treatment for multiple myeloma (MM).

However, MorphoSys said it will complete the ongoing phase 1/2a trial of MOR202, and I-Mab Biopharma will continue developing MOR202 as an MM therapy for the Greater China region.

MOR202 is a human monoclonal HuCAL antibody directed against CD38, a validated target in MM.

MorphoSys is testing MOR202 in combination with other drugs in a phase 1/2a trial of patients with relapsed/refractory MM (NCT01421186).

The patients were assigned to receive MOR202 plus dexamethasone (Dex), MOR202 plus lenalidomide (Len) and Dex, or MOR202 plus pomalidomide (Pom) and Dex.

Results from this study were presented at the 2016 Annual Meeting of the German, Austrian and Swiss Societies for Hematology and Medical Oncology.

Data were reported for 38 patients—18 who had received MOR202 plus Dex, 7 who had received MOR202 plus Pom and Dex, and 13 who had received MOR202 plus Len and Dex.

The researchers said the maximum-tolerated dose of MOR202, alone or in combination, had not yet been reached. However, the data suggested MOR202 can be safely administered as a 2-hour intravenous infusion at doses up to 16 mg/kg.

The most frequent grade 3 or higher adverse events observed were hematologic in nature (leukopenia, lymphopenia, neutropenia, thrombocytopenia, and anemia).

One patient discontinued treatment due to an adverse event (decrease in platelet count) that may have been caused by MOR202 or Dex. One patient developed a transient anti-MOR202 antibody response.

There were no treatment-related deaths.

Efficacy data were available for 31 of the 38 patients. Fifteen patients responded (2 with complete responses). There were 7 responses in the Len/Dex arm, 5 in the Dex arm, and 3 in the Pom/Dex arm. Twelve responses were ongoing for up to 56 weeks.

MorphoSys said it expects to present final results from this study at an upcoming medical conference.

MorphoSys also said it will continue to support I-Mab Biopharma’s development of MOR202 in Greater China (China, Taiwan, Hong Kong, and Macao).

In November 2017, MorphoSys and I-Mab entered into an exclusive regional licensing agreement to develop and commercialize MOR202 in Greater China. I-Mab assumed exclusive responsibility for all subsequent development and commercialization of MOR202 in the agreed territory.

Micrograph showing MM

MorphoSys AG has decided to stop developing MOR202 as a treatment for multiple myeloma (MM).

However, MorphoSys said it will complete the ongoing phase 1/2a trial of MOR202, and I-Mab Biopharma will continue developing MOR202 as an MM therapy for the Greater China region.

MOR202 is a human monoclonal HuCAL antibody directed against CD38, a validated target in MM.

MorphoSys is testing MOR202 in combination with other drugs in a phase 1/2a trial of patients with relapsed/refractory MM (NCT01421186).

The patients were assigned to receive MOR202 plus dexamethasone (Dex), MOR202 plus lenalidomide (Len) and Dex, or MOR202 plus pomalidomide (Pom) and Dex.

Results from this study were presented at the 2016 Annual Meeting of the German, Austrian and Swiss Societies for Hematology and Medical Oncology.

Data were reported for 38 patients—18 who had received MOR202 plus Dex, 7 who had received MOR202 plus Pom and Dex, and 13 who had received MOR202 plus Len and Dex.

The researchers said the maximum-tolerated dose of MOR202, alone or in combination, had not yet been reached. However, the data suggested MOR202 can be safely administered as a 2-hour intravenous infusion at doses up to 16 mg/kg.

The most frequent grade 3 or higher adverse events observed were hematologic in nature (leukopenia, lymphopenia, neutropenia, thrombocytopenia, and anemia).

One patient discontinued treatment due to an adverse event (decrease in platelet count) that may have been caused by MOR202 or Dex. One patient developed a transient anti-MOR202 antibody response.

There were no treatment-related deaths.

Efficacy data were available for 31 of the 38 patients. Fifteen patients responded (2 with complete responses). There were 7 responses in the Len/Dex arm, 5 in the Dex arm, and 3 in the Pom/Dex arm. Twelve responses were ongoing for up to 56 weeks.

MorphoSys said it expects to present final results from this study at an upcoming medical conference.

MorphoSys also said it will continue to support I-Mab Biopharma’s development of MOR202 in Greater China (China, Taiwan, Hong Kong, and Macao).

In November 2017, MorphoSys and I-Mab entered into an exclusive regional licensing agreement to develop and commercialize MOR202 in Greater China. I-Mab assumed exclusive responsibility for all subsequent development and commercialization of MOR202 in the agreed territory.

Micrograph showing MM

MorphoSys AG has decided to stop developing MOR202 as a treatment for multiple myeloma (MM).

However, MorphoSys said it will complete the ongoing phase 1/2a trial of MOR202, and I-Mab Biopharma will continue developing MOR202 as an MM therapy for the Greater China region.

MOR202 is a human monoclonal HuCAL antibody directed against CD38, a validated target in MM.

MorphoSys is testing MOR202 in combination with other drugs in a phase 1/2a trial of patients with relapsed/refractory MM (NCT01421186).

The patients were assigned to receive MOR202 plus dexamethasone (Dex), MOR202 plus lenalidomide (Len) and Dex, or MOR202 plus pomalidomide (Pom) and Dex.

Results from this study were presented at the 2016 Annual Meeting of the German, Austrian and Swiss Societies for Hematology and Medical Oncology.

Data were reported for 38 patients—18 who had received MOR202 plus Dex, 7 who had received MOR202 plus Pom and Dex, and 13 who had received MOR202 plus Len and Dex.

The researchers said the maximum-tolerated dose of MOR202, alone or in combination, had not yet been reached. However, the data suggested MOR202 can be safely administered as a 2-hour intravenous infusion at doses up to 16 mg/kg.

The most frequent grade 3 or higher adverse events observed were hematologic in nature (leukopenia, lymphopenia, neutropenia, thrombocytopenia, and anemia).

One patient discontinued treatment due to an adverse event (decrease in platelet count) that may have been caused by MOR202 or Dex. One patient developed a transient anti-MOR202 antibody response.

There were no treatment-related deaths.

Efficacy data were available for 31 of the 38 patients. Fifteen patients responded (2 with complete responses). There were 7 responses in the Len/Dex arm, 5 in the Dex arm, and 3 in the Pom/Dex arm. Twelve responses were ongoing for up to 56 weeks.

MorphoSys said it expects to present final results from this study at an upcoming medical conference.

MorphoSys also said it will continue to support I-Mab Biopharma’s development of MOR202 in Greater China (China, Taiwan, Hong Kong, and Macao).

In November 2017, MorphoSys and I-Mab entered into an exclusive regional licensing agreement to develop and commercialize MOR202 in Greater China. I-Mab assumed exclusive responsibility for all subsequent development and commercialization of MOR202 in the agreed territory.

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.