Multiple Myeloma

Micrograph showing MM

ROME—Early results of a pilot study indicate that a 3-agent combination regimen can produce responses in patients with relapsed or refractory multiple myeloma (MM).

The treatment consists of carfilzomib, dexamethasone, and pelareorep (Reolysin), a proprietary isolate of human reovirus (Type 3 Dearing strain).

All 8 evaluable patients treated with this regimen experienced an objective response, although 1 patient later progressed.

The investigators said the regimen has been relatively well tolerated, but most patients experience flu-like symptoms over the first week of treatment. And cytopenias, especially thrombocytopenia, are common.

Douglas Sborov, MD, of The Ohio State University in Columbus, and his colleagues presented this research at the 15th International Myeloma Workshop (poster #379).

The investigators noted that this is the first time a pelareorep-based combination has been tested in relapsed MM patients. A previous single-agent study indicated that pelareorep was well tolerated, and preclinical research has shown that reovirus and carfilzomib synergize to kill MM cells.

To expand upon these results, Dr Sborov and colleagues began testing pelareorep with carfilzomib and dexamethasone in patients with relapsed/refractory MM. The ongoing study, known as NCI-9603, is sponsored by the National Cancer Institute.

Of the 8 patients enrolled thus far, 5 had intermediate- or high-risk disease at baseline, and 1 patient was dialysis-dependent. The median age was 63 (range, 43-70).

Patients had received a median of 2 prior lines of therapy (range, 1-6) and a median of 4 prior treatments (range, 2-8). All of the patients had received lenalidomide, 1 had received carfilzomib, and 4 were refractory to bortezomib.

For the current study, patients were assigned to receive dexamethasone, carfilzomib over 10 minutes, and pelareorep over 60 minutes on days 1, 2, 8, 9, 15, and 16. Treatment is set to repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients who achieve a minimal response or better may reduce treatment to days 1, 8, and 15 after 4 courses and to days 1 and 15 after 12 courses.

Treatment results

The investigators said the treatment produced a significant (P=0.005) increase in caspase-3, a marker associated with apoptotic cell death.

The combination was also associated with an increased infiltration of CD8+ T cells and the significant (P=0.005) upregulation of PD-L1, suggesting the addition of a PD-1 or PD-L1 inhibitor might further optimize the regimen.

All 8 patients experienced an objective response to treatment, as measured by changes in blood monoclonal protein. Two patients had a very good partial response, 3 had a partial response, and 3 had a minor response.

Five of the patients remain on study. The dialysis-dependent patient discontinued treatment due to progression after 3 treatment cycles. And 2 patients discontinued treatment due to dose-limiting toxicities after 2 doses.

One of the patients with dose-limiting toxicities had grade 4 myocarditis, grade 3 left ventricular dysfunction, and grade 4 respiratory failure possibly attributable to pelareorep and carfilzomib. The other patient had lower gastrointestinal bleeding that was not attributed to treatment.

Adverse events in cycle 1 that were possibly, likely, or definitely attributed to treatment included hypertension (n=5), thrombocytopenia (n=4), anemia (n=4), dyspnea on exertion (n=4), fatigue (n=4), myalgia (n=3), fever (n=2), leukopenia (n=2), lymphopenia (n=2), nausea (n=2), and diarrhea (n=2).

For more details, visit the Oncolytics Biotech Inc. website to view the poster. Oncolytics is the company developing pelareorep.

Micrograph showing MM

ROME—Early results of a pilot study indicate that a 3-agent combination regimen can produce responses in patients with relapsed or refractory multiple myeloma (MM).

The treatment consists of carfilzomib, dexamethasone, and pelareorep (Reolysin), a proprietary isolate of human reovirus (Type 3 Dearing strain).

All 8 evaluable patients treated with this regimen experienced an objective response, although 1 patient later progressed.

The investigators said the regimen has been relatively well tolerated, but most patients experience flu-like symptoms over the first week of treatment. And cytopenias, especially thrombocytopenia, are common.

Douglas Sborov, MD, of The Ohio State University in Columbus, and his colleagues presented this research at the 15th International Myeloma Workshop (poster #379).

The investigators noted that this is the first time a pelareorep-based combination has been tested in relapsed MM patients. A previous single-agent study indicated that pelareorep was well tolerated, and preclinical research has shown that reovirus and carfilzomib synergize to kill MM cells.

To expand upon these results, Dr Sborov and colleagues began testing pelareorep with carfilzomib and dexamethasone in patients with relapsed/refractory MM. The ongoing study, known as NCI-9603, is sponsored by the National Cancer Institute.

Of the 8 patients enrolled thus far, 5 had intermediate- or high-risk disease at baseline, and 1 patient was dialysis-dependent. The median age was 63 (range, 43-70).

Patients had received a median of 2 prior lines of therapy (range, 1-6) and a median of 4 prior treatments (range, 2-8). All of the patients had received lenalidomide, 1 had received carfilzomib, and 4 were refractory to bortezomib.

For the current study, patients were assigned to receive dexamethasone, carfilzomib over 10 minutes, and pelareorep over 60 minutes on days 1, 2, 8, 9, 15, and 16. Treatment is set to repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients who achieve a minimal response or better may reduce treatment to days 1, 8, and 15 after 4 courses and to days 1 and 15 after 12 courses.

Treatment results

The investigators said the treatment produced a significant (P=0.005) increase in caspase-3, a marker associated with apoptotic cell death.

The combination was also associated with an increased infiltration of CD8+ T cells and the significant (P=0.005) upregulation of PD-L1, suggesting the addition of a PD-1 or PD-L1 inhibitor might further optimize the regimen.

All 8 patients experienced an objective response to treatment, as measured by changes in blood monoclonal protein. Two patients had a very good partial response, 3 had a partial response, and 3 had a minor response.

Five of the patients remain on study. The dialysis-dependent patient discontinued treatment due to progression after 3 treatment cycles. And 2 patients discontinued treatment due to dose-limiting toxicities after 2 doses.

One of the patients with dose-limiting toxicities had grade 4 myocarditis, grade 3 left ventricular dysfunction, and grade 4 respiratory failure possibly attributable to pelareorep and carfilzomib. The other patient had lower gastrointestinal bleeding that was not attributed to treatment.

Adverse events in cycle 1 that were possibly, likely, or definitely attributed to treatment included hypertension (n=5), thrombocytopenia (n=4), anemia (n=4), dyspnea on exertion (n=4), fatigue (n=4), myalgia (n=3), fever (n=2), leukopenia (n=2), lymphopenia (n=2), nausea (n=2), and diarrhea (n=2).

For more details, visit the Oncolytics Biotech Inc. website to view the poster. Oncolytics is the company developing pelareorep.

Micrograph showing MM

ROME—Early results of a pilot study indicate that a 3-agent combination regimen can produce responses in patients with relapsed or refractory multiple myeloma (MM).

The treatment consists of carfilzomib, dexamethasone, and pelareorep (Reolysin), a proprietary isolate of human reovirus (Type 3 Dearing strain).

All 8 evaluable patients treated with this regimen experienced an objective response, although 1 patient later progressed.

The investigators said the regimen has been relatively well tolerated, but most patients experience flu-like symptoms over the first week of treatment. And cytopenias, especially thrombocytopenia, are common.

Douglas Sborov, MD, of The Ohio State University in Columbus, and his colleagues presented this research at the 15th International Myeloma Workshop (poster #379).

The investigators noted that this is the first time a pelareorep-based combination has been tested in relapsed MM patients. A previous single-agent study indicated that pelareorep was well tolerated, and preclinical research has shown that reovirus and carfilzomib synergize to kill MM cells.

To expand upon these results, Dr Sborov and colleagues began testing pelareorep with carfilzomib and dexamethasone in patients with relapsed/refractory MM. The ongoing study, known as NCI-9603, is sponsored by the National Cancer Institute.

Of the 8 patients enrolled thus far, 5 had intermediate- or high-risk disease at baseline, and 1 patient was dialysis-dependent. The median age was 63 (range, 43-70).

Patients had received a median of 2 prior lines of therapy (range, 1-6) and a median of 4 prior treatments (range, 2-8). All of the patients had received lenalidomide, 1 had received carfilzomib, and 4 were refractory to bortezomib.

For the current study, patients were assigned to receive dexamethasone, carfilzomib over 10 minutes, and pelareorep over 60 minutes on days 1, 2, 8, 9, 15, and 16. Treatment is set to repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients who achieve a minimal response or better may reduce treatment to days 1, 8, and 15 after 4 courses and to days 1 and 15 after 12 courses.

Treatment results

The investigators said the treatment produced a significant (P=0.005) increase in caspase-3, a marker associated with apoptotic cell death.

The combination was also associated with an increased infiltration of CD8+ T cells and the significant (P=0.005) upregulation of PD-L1, suggesting the addition of a PD-1 or PD-L1 inhibitor might further optimize the regimen.

All 8 patients experienced an objective response to treatment, as measured by changes in blood monoclonal protein. Two patients had a very good partial response, 3 had a partial response, and 3 had a minor response.

Five of the patients remain on study. The dialysis-dependent patient discontinued treatment due to progression after 3 treatment cycles. And 2 patients discontinued treatment due to dose-limiting toxicities after 2 doses.

One of the patients with dose-limiting toxicities had grade 4 myocarditis, grade 3 left ventricular dysfunction, and grade 4 respiratory failure possibly attributable to pelareorep and carfilzomib. The other patient had lower gastrointestinal bleeding that was not attributed to treatment.

Adverse events in cycle 1 that were possibly, likely, or definitely attributed to treatment included hypertension (n=5), thrombocytopenia (n=4), anemia (n=4), dyspnea on exertion (n=4), fatigue (n=4), myalgia (n=3), fever (n=2), leukopenia (n=2), lymphopenia (n=2), nausea (n=2), and diarrhea (n=2).

For more details, visit the Oncolytics Biotech Inc. website to view the poster. Oncolytics is the company developing pelareorep.

 

 

Cancer patient receiving

chemotherapy

Photo by Rhoda Baer

 

VIENNA—Results of the EUROCARE-5 study have revealed regional differences in survival for European patients with hematologic malignancies.

The data showed regional variations in 5-year relative survival rates for a number of cancers.

But the differences were particularly pronounced for leukemias, non-Hodgkin lymphomas (NHLs), and plasma cell neoplasms (PCNs).

Milena Sant, MD, of the Fondazione IRCCS Istituto Nazionale dei Tumori in Milan, Italy, presented these results at the 2015 European Cancer Congress (LBA 1).

Data from this study have also been published in several articles in the October 2015 issue of the European Journal of Cancer.

EUROCARE-5 includes records from 22 million cancer patients diagnosed between 1978 and 2007. The latest data encompass more than 10 million patients (ages 15 and older) diagnosed from 1995 to 2007 and followed up to 2008.

The data came from 107 cancer registries in 29 countries. The researchers estimated 5-year relative survival and trends from 1999 to 2007 according to region—Ireland/UK, Northern Europe, Central Europe, Southern Europe, and Eastern Europe.

“In general, 5-year relative survival—survival that is adjusted for causes of death other than cancer—increased steadily over time in Europe, particularly in Eastern Europe, for most cancers,” Dr Sant said.

“However, the most dramatic geographical variations were observed for cancers of the blood where there have been recent advances in treatment, such as chronic myeloid and lymphocytic leukemias, non-Hodgkin lymphoma and 2 of its subtypes (follicular and diffuse large B-cell lymphoma), and multiple myeloma. Hodgkin lymphoma was the exception, with smaller regional variations and a fairly good prognosis in most countries.”

Hodgkin lymphoma and NHL

Of all the hematologic malignancies, 5-year relative survival was highest for Hodgkin lymphoma, at 80.8% (40,625 cases).  Five-year survival was 79.4% in Ireland and the UK, 85% in Northern countries, and 74.3% in Eastern Europe, which was significantly below the European average (P<0.0001).

For NHL, the 5-year relative survival was 59.4% (329,204 cases). Survival rates for NHL patients ranged from 49.7% in Eastern Europe to 63.3% in Northern Europe.

CLL/SLL

For chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), the 5-year relative survival was 70.4% (81,914 cases). CLL/SLL survival ranged from 58% in Eastern Europe to about 74% in Central and Northern Europe.

The researchers noted that between-country variations in CLL/SLL survival were high in all regions. Outliers that were significantly below the regional average were Austria (67%), Croatia (52%), and Bulgaria (45.5%).

PCNs

PCNs included multiple myeloma, plasmacytoma, and plasma cell leukemias. The 5-year relative survival for all PCNs was 39.2% (94,024 cases).

PCN survival rates were lowest in Eastern Europe (31.7%), slightly higher in the UK/Ireland (35.9%), and between 39.1% and 42% in the rest of Europe.

Myeloid leukemias

Of all the hematologic malignancies, 5-year relative survival was poorest for patients with acute myeloid leukemia (AML), at 17.1% (57,026 cases).

AML survival rates in Ireland/UK (15.0%) and Eastern Europe (13.0%) were significantly below the European average. But AML survival in Sweden, Belgium, France, and Germany was significantly higher than the average (P<0.005).

Five-year relative survival for chronic myeloid leukemia (CML) was 52.9% (17,713 cases).

Of all the hematologic malignancies, the survival gap between Eastern Europe and the rest of Europe was highest for CML. Five-year survival for CML patients was 33% in Eastern Europe and ranged from 51% to 58% in the rest of Europe.

The researchers also said there were striking survival variations by country in all areas. They found significant deviations from the regional average in Sweden (69.7%), Scotland (64.6%), France (71.7%), Austria (48.2%), Croatia (37.8%), Estonia (48.9%), Czech Republic (45.2%), and Latvia (22.1%).

“Results from EUROCARE can help to identify regions of low survival where action is needed to improve patients’ outcomes,” Dr Sant noted.

“Population-based survival information is essential for physicians, policy-makers, administrators, researchers, and patient organizations who deal with the needs of cancer patients, as well as with the issue of the growing expenditure on healthcare.”

 

 

Cancer patient receiving

chemotherapy

Photo by Rhoda Baer

 

VIENNA—Results of the EUROCARE-5 study have revealed regional differences in survival for European patients with hematologic malignancies.

The data showed regional variations in 5-year relative survival rates for a number of cancers.

But the differences were particularly pronounced for leukemias, non-Hodgkin lymphomas (NHLs), and plasma cell neoplasms (PCNs).

Milena Sant, MD, of the Fondazione IRCCS Istituto Nazionale dei Tumori in Milan, Italy, presented these results at the 2015 European Cancer Congress (LBA 1).

Data from this study have also been published in several articles in the October 2015 issue of the European Journal of Cancer.

EUROCARE-5 includes records from 22 million cancer patients diagnosed between 1978 and 2007. The latest data encompass more than 10 million patients (ages 15 and older) diagnosed from 1995 to 2007 and followed up to 2008.

The data came from 107 cancer registries in 29 countries. The researchers estimated 5-year relative survival and trends from 1999 to 2007 according to region—Ireland/UK, Northern Europe, Central Europe, Southern Europe, and Eastern Europe.

“In general, 5-year relative survival—survival that is adjusted for causes of death other than cancer—increased steadily over time in Europe, particularly in Eastern Europe, for most cancers,” Dr Sant said.

“However, the most dramatic geographical variations were observed for cancers of the blood where there have been recent advances in treatment, such as chronic myeloid and lymphocytic leukemias, non-Hodgkin lymphoma and 2 of its subtypes (follicular and diffuse large B-cell lymphoma), and multiple myeloma. Hodgkin lymphoma was the exception, with smaller regional variations and a fairly good prognosis in most countries.”

Hodgkin lymphoma and NHL

Of all the hematologic malignancies, 5-year relative survival was highest for Hodgkin lymphoma, at 80.8% (40,625 cases).  Five-year survival was 79.4% in Ireland and the UK, 85% in Northern countries, and 74.3% in Eastern Europe, which was significantly below the European average (P<0.0001).

For NHL, the 5-year relative survival was 59.4% (329,204 cases). Survival rates for NHL patients ranged from 49.7% in Eastern Europe to 63.3% in Northern Europe.

CLL/SLL

For chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), the 5-year relative survival was 70.4% (81,914 cases). CLL/SLL survival ranged from 58% in Eastern Europe to about 74% in Central and Northern Europe.

The researchers noted that between-country variations in CLL/SLL survival were high in all regions. Outliers that were significantly below the regional average were Austria (67%), Croatia (52%), and Bulgaria (45.5%).

PCNs

PCNs included multiple myeloma, plasmacytoma, and plasma cell leukemias. The 5-year relative survival for all PCNs was 39.2% (94,024 cases).

PCN survival rates were lowest in Eastern Europe (31.7%), slightly higher in the UK/Ireland (35.9%), and between 39.1% and 42% in the rest of Europe.

Myeloid leukemias

Of all the hematologic malignancies, 5-year relative survival was poorest for patients with acute myeloid leukemia (AML), at 17.1% (57,026 cases).

AML survival rates in Ireland/UK (15.0%) and Eastern Europe (13.0%) were significantly below the European average. But AML survival in Sweden, Belgium, France, and Germany was significantly higher than the average (P<0.005).

Five-year relative survival for chronic myeloid leukemia (CML) was 52.9% (17,713 cases).

Of all the hematologic malignancies, the survival gap between Eastern Europe and the rest of Europe was highest for CML. Five-year survival for CML patients was 33% in Eastern Europe and ranged from 51% to 58% in the rest of Europe.

The researchers also said there were striking survival variations by country in all areas. They found significant deviations from the regional average in Sweden (69.7%), Scotland (64.6%), France (71.7%), Austria (48.2%), Croatia (37.8%), Estonia (48.9%), Czech Republic (45.2%), and Latvia (22.1%).

“Results from EUROCARE can help to identify regions of low survival where action is needed to improve patients’ outcomes,” Dr Sant noted.

“Population-based survival information is essential for physicians, policy-makers, administrators, researchers, and patient organizations who deal with the needs of cancer patients, as well as with the issue of the growing expenditure on healthcare.”

 

 

Cancer patient receiving

chemotherapy

Photo by Rhoda Baer

 

VIENNA—Results of the EUROCARE-5 study have revealed regional differences in survival for European patients with hematologic malignancies.

The data showed regional variations in 5-year relative survival rates for a number of cancers.

But the differences were particularly pronounced for leukemias, non-Hodgkin lymphomas (NHLs), and plasma cell neoplasms (PCNs).

Milena Sant, MD, of the Fondazione IRCCS Istituto Nazionale dei Tumori in Milan, Italy, presented these results at the 2015 European Cancer Congress (LBA 1).

Data from this study have also been published in several articles in the October 2015 issue of the European Journal of Cancer.

EUROCARE-5 includes records from 22 million cancer patients diagnosed between 1978 and 2007. The latest data encompass more than 10 million patients (ages 15 and older) diagnosed from 1995 to 2007 and followed up to 2008.

The data came from 107 cancer registries in 29 countries. The researchers estimated 5-year relative survival and trends from 1999 to 2007 according to region—Ireland/UK, Northern Europe, Central Europe, Southern Europe, and Eastern Europe.

“In general, 5-year relative survival—survival that is adjusted for causes of death other than cancer—increased steadily over time in Europe, particularly in Eastern Europe, for most cancers,” Dr Sant said.

“However, the most dramatic geographical variations were observed for cancers of the blood where there have been recent advances in treatment, such as chronic myeloid and lymphocytic leukemias, non-Hodgkin lymphoma and 2 of its subtypes (follicular and diffuse large B-cell lymphoma), and multiple myeloma. Hodgkin lymphoma was the exception, with smaller regional variations and a fairly good prognosis in most countries.”

Hodgkin lymphoma and NHL

Of all the hematologic malignancies, 5-year relative survival was highest for Hodgkin lymphoma, at 80.8% (40,625 cases).  Five-year survival was 79.4% in Ireland and the UK, 85% in Northern countries, and 74.3% in Eastern Europe, which was significantly below the European average (P<0.0001).

For NHL, the 5-year relative survival was 59.4% (329,204 cases). Survival rates for NHL patients ranged from 49.7% in Eastern Europe to 63.3% in Northern Europe.

CLL/SLL

For chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), the 5-year relative survival was 70.4% (81,914 cases). CLL/SLL survival ranged from 58% in Eastern Europe to about 74% in Central and Northern Europe.

The researchers noted that between-country variations in CLL/SLL survival were high in all regions. Outliers that were significantly below the regional average were Austria (67%), Croatia (52%), and Bulgaria (45.5%).

PCNs

PCNs included multiple myeloma, plasmacytoma, and plasma cell leukemias. The 5-year relative survival for all PCNs was 39.2% (94,024 cases).

PCN survival rates were lowest in Eastern Europe (31.7%), slightly higher in the UK/Ireland (35.9%), and between 39.1% and 42% in the rest of Europe.

Myeloid leukemias

Of all the hematologic malignancies, 5-year relative survival was poorest for patients with acute myeloid leukemia (AML), at 17.1% (57,026 cases).

AML survival rates in Ireland/UK (15.0%) and Eastern Europe (13.0%) were significantly below the European average. But AML survival in Sweden, Belgium, France, and Germany was significantly higher than the average (P<0.005).

Five-year relative survival for chronic myeloid leukemia (CML) was 52.9% (17,713 cases).

Of all the hematologic malignancies, the survival gap between Eastern Europe and the rest of Europe was highest for CML. Five-year survival for CML patients was 33% in Eastern Europe and ranged from 51% to 58% in the rest of Europe.

The researchers also said there were striking survival variations by country in all areas. They found significant deviations from the regional average in Sweden (69.7%), Scotland (64.6%), France (71.7%), Austria (48.2%), Croatia (37.8%), Estonia (48.9%), Czech Republic (45.2%), and Latvia (22.1%).

“Results from EUROCARE can help to identify regions of low survival where action is needed to improve patients’ outcomes,” Dr Sant noted.

“Population-based survival information is essential for physicians, policy-makers, administrators, researchers, and patient organizations who deal with the needs of cancer patients, as well as with the issue of the growing expenditure on healthcare.”

Micrograph showing

multiple myeloma

ROME—Combination therapy incorporating a novel monoclonal antibody (mAb) can provide “encouraging, long-lasting tumor control” in heavily pretreated patients with relapsed/refractory multiple myeloma (MM), according to investigators.

The mAb, MOR202, was also considered to be well-tolerated in this ongoing phase 1/2a study.

Early results from this study were presented at the 15th International Myeloma Workshop (poster #156). The study was sponsored by MorphoSys AG, makers of MOR202. The poster is available on the company’s website.

MOR202 is a HuCAL-derived mAb directed against CD38. In the phase 1/2a study, 50 MM patients have received the drug thus far.

At baseline, the patients’ median age was 67. They had received a median of 4 prior therapies, including bortezomib (98%), lenalidomide (92%), melphalan (92%), cyclophosphamide (76%), doxorubicin (60%), thalidomide (32%), pomalidomide (14%), carfilzomib (6%), elotuzumab (4%), and panobinostat (4%). Seventy-six percent had received a stem cell transplant.

Study design

The study consists of several parts and dosing cohorts in which the investigators are assessing MOR202 alone or in combination with other agents.

Treatment in Part A consists of a 2-hour intravenous infusion of MOR202 once every 2 weeks at several different doses: 0.01 mg/kg , 0.04 mg/kg, 0.15 mg/kg,  0.5 mg/kg, 1.5 mg/kg, 4.0 mg/kg, 8.0 mg/kg, or 16.0 mg/kg.

Part B is a 2-hour intravenous infusion of MOR202 once a week at 4 mg/kg, 8 mg/kg, or 16 mg/kg.

Part C is dexamethasone plus MOR202 once a week at 4 mg/kg, 8 mg/kg, or 16 mg/kg.

Part D is pomalidomide, dexamethasone, and MOR202 once a week at 8 mg/kg or 16 mg/kg.

Part E is lenalidomide, dexamethasone, and MOR202 once a week at 8 mg/kg or 16 mg/kg.

In the confirmatory cohorts, patients receive MOR202 with or without dexamethasone once a week or once every 2 weeks, MOR202 with pomalidomide and dexamethasone once a week, or MOR202 with lenalidomide and dexamethasone once a week.

Efficacy

Of the 50 patients treated thus far, 27 were evaluable for efficacy. One patient achieved a very good partial response, 2 had a partial response, and 2 had a minor response. Eleven patients had stable disease, and 11 progressed.

The very good partial response occurred in a patient receiving weekly MOR202 at 4 mg/kg plus dexamethasone.

One partial response occurred in a patient receiving weekly MOR202 at 8 mg/kg plus dexamethasone. The other occurred in a patient receiving weekly MOR202 at 8 mg/kg plus dexamethasone and pomalidomide.

One minor response occurred in a patient receiving weekly MOR202 at 8 mg/kg plus dexamethasone and lenalidomide. The other occurred in a patient receiving weekly MOR202 at 16 mg/kg plus dexamethasone.

“[T]he preliminary efficacy seen so far with MOR202 as single agent and in combinations is promising,” said investigator Marc-Steffen Raab, MD, of Heidelberg University Hospital and the German Cancer Research Center DKFZ in Heidelberg, Germany.

Safety

All 50 patients were evaluable for safety. Ninety-eight percent experienced an adverse event (AE), 66% of which were grade 3 or higher.

The most frequent AEs (overall and grade 3 or higher) were anemia (34%, 6%), leukopenia (30%, 10%), neutropenia (20%, 10%), thrombocytopenia (18%, 8%), fatigue (30%, 0%), nausea (22%, 0%), diarrhea (20%, 0%), and headache (16%, 0%).

Thirty-six percent of patients discontinued MOR202 due to treatment-emergent AEs. However, only 6% (n=3) of these AEs were considered possibly related to MOR202.

Infusion-related reactions occurred in 15 patients (30%). One of these patients received dexamethasone as well and experienced an infusion-related reaction (grade 1).

In the absence of dexamethasone, nearly all infusion reactions were grade 1-2. The exception was 1 patient with a grade 3 reaction that was mainly limited to the first infusion.

The maximum tolerated dose of MOR202 has not been reached.

“Considering the low rate of infusion reactions, even in cohorts without dexamethasone, the short infusion time, and other aspects, MOR202 may turn out to be an excellent choice in terms of safety and tolerability,” Dr Raab concluded.

Micrograph showing

multiple myeloma

ROME—Combination therapy incorporating a novel monoclonal antibody (mAb) can provide “encouraging, long-lasting tumor control” in heavily pretreated patients with relapsed/refractory multiple myeloma (MM), according to investigators.

The mAb, MOR202, was also considered to be well-tolerated in this ongoing phase 1/2a study.

Early results from this study were presented at the 15th International Myeloma Workshop (poster #156). The study was sponsored by MorphoSys AG, makers of MOR202. The poster is available on the company’s website.

MOR202 is a HuCAL-derived mAb directed against CD38. In the phase 1/2a study, 50 MM patients have received the drug thus far.

At baseline, the patients’ median age was 67. They had received a median of 4 prior therapies, including bortezomib (98%), lenalidomide (92%), melphalan (92%), cyclophosphamide (76%), doxorubicin (60%), thalidomide (32%), pomalidomide (14%), carfilzomib (6%), elotuzumab (4%), and panobinostat (4%). Seventy-six percent had received a stem cell transplant.

Study design

The study consists of several parts and dosing cohorts in which the investigators are assessing MOR202 alone or in combination with other agents.

Treatment in Part A consists of a 2-hour intravenous infusion of MOR202 once every 2 weeks at several different doses: 0.01 mg/kg , 0.04 mg/kg, 0.15 mg/kg,  0.5 mg/kg, 1.5 mg/kg, 4.0 mg/kg, 8.0 mg/kg, or 16.0 mg/kg.

Part B is a 2-hour intravenous infusion of MOR202 once a week at 4 mg/kg, 8 mg/kg, or 16 mg/kg.

Part C is dexamethasone plus MOR202 once a week at 4 mg/kg, 8 mg/kg, or 16 mg/kg.

Part D is pomalidomide, dexamethasone, and MOR202 once a week at 8 mg/kg or 16 mg/kg.

Part E is lenalidomide, dexamethasone, and MOR202 once a week at 8 mg/kg or 16 mg/kg.

In the confirmatory cohorts, patients receive MOR202 with or without dexamethasone once a week or once every 2 weeks, MOR202 with pomalidomide and dexamethasone once a week, or MOR202 with lenalidomide and dexamethasone once a week.

Efficacy

Of the 50 patients treated thus far, 27 were evaluable for efficacy. One patient achieved a very good partial response, 2 had a partial response, and 2 had a minor response. Eleven patients had stable disease, and 11 progressed.

The very good partial response occurred in a patient receiving weekly MOR202 at 4 mg/kg plus dexamethasone.

One partial response occurred in a patient receiving weekly MOR202 at 8 mg/kg plus dexamethasone. The other occurred in a patient receiving weekly MOR202 at 8 mg/kg plus dexamethasone and pomalidomide.

One minor response occurred in a patient receiving weekly MOR202 at 8 mg/kg plus dexamethasone and lenalidomide. The other occurred in a patient receiving weekly MOR202 at 16 mg/kg plus dexamethasone.

“[T]he preliminary efficacy seen so far with MOR202 as single agent and in combinations is promising,” said investigator Marc-Steffen Raab, MD, of Heidelberg University Hospital and the German Cancer Research Center DKFZ in Heidelberg, Germany.

Safety

All 50 patients were evaluable for safety. Ninety-eight percent experienced an adverse event (AE), 66% of which were grade 3 or higher.

The most frequent AEs (overall and grade 3 or higher) were anemia (34%, 6%), leukopenia (30%, 10%), neutropenia (20%, 10%), thrombocytopenia (18%, 8%), fatigue (30%, 0%), nausea (22%, 0%), diarrhea (20%, 0%), and headache (16%, 0%).

Thirty-six percent of patients discontinued MOR202 due to treatment-emergent AEs. However, only 6% (n=3) of these AEs were considered possibly related to MOR202.

Infusion-related reactions occurred in 15 patients (30%). One of these patients received dexamethasone as well and experienced an infusion-related reaction (grade 1).

In the absence of dexamethasone, nearly all infusion reactions were grade 1-2. The exception was 1 patient with a grade 3 reaction that was mainly limited to the first infusion.

The maximum tolerated dose of MOR202 has not been reached.

“Considering the low rate of infusion reactions, even in cohorts without dexamethasone, the short infusion time, and other aspects, MOR202 may turn out to be an excellent choice in terms of safety and tolerability,” Dr Raab concluded.

Micrograph showing

multiple myeloma

ROME—Combination therapy incorporating a novel monoclonal antibody (mAb) can provide “encouraging, long-lasting tumor control” in heavily pretreated patients with relapsed/refractory multiple myeloma (MM), according to investigators.

The mAb, MOR202, was also considered to be well-tolerated in this ongoing phase 1/2a study.

Early results from this study were presented at the 15th International Myeloma Workshop (poster #156). The study was sponsored by MorphoSys AG, makers of MOR202. The poster is available on the company’s website.

MOR202 is a HuCAL-derived mAb directed against CD38. In the phase 1/2a study, 50 MM patients have received the drug thus far.

At baseline, the patients’ median age was 67. They had received a median of 4 prior therapies, including bortezomib (98%), lenalidomide (92%), melphalan (92%), cyclophosphamide (76%), doxorubicin (60%), thalidomide (32%), pomalidomide (14%), carfilzomib (6%), elotuzumab (4%), and panobinostat (4%). Seventy-six percent had received a stem cell transplant.

Study design

The study consists of several parts and dosing cohorts in which the investigators are assessing MOR202 alone or in combination with other agents.

Treatment in Part A consists of a 2-hour intravenous infusion of MOR202 once every 2 weeks at several different doses: 0.01 mg/kg , 0.04 mg/kg, 0.15 mg/kg,  0.5 mg/kg, 1.5 mg/kg, 4.0 mg/kg, 8.0 mg/kg, or 16.0 mg/kg.

Part B is a 2-hour intravenous infusion of MOR202 once a week at 4 mg/kg, 8 mg/kg, or 16 mg/kg.

Part C is dexamethasone plus MOR202 once a week at 4 mg/kg, 8 mg/kg, or 16 mg/kg.

Part D is pomalidomide, dexamethasone, and MOR202 once a week at 8 mg/kg or 16 mg/kg.

Part E is lenalidomide, dexamethasone, and MOR202 once a week at 8 mg/kg or 16 mg/kg.

In the confirmatory cohorts, patients receive MOR202 with or without dexamethasone once a week or once every 2 weeks, MOR202 with pomalidomide and dexamethasone once a week, or MOR202 with lenalidomide and dexamethasone once a week.

Efficacy

Of the 50 patients treated thus far, 27 were evaluable for efficacy. One patient achieved a very good partial response, 2 had a partial response, and 2 had a minor response. Eleven patients had stable disease, and 11 progressed.

The very good partial response occurred in a patient receiving weekly MOR202 at 4 mg/kg plus dexamethasone.

One partial response occurred in a patient receiving weekly MOR202 at 8 mg/kg plus dexamethasone. The other occurred in a patient receiving weekly MOR202 at 8 mg/kg plus dexamethasone and pomalidomide.

One minor response occurred in a patient receiving weekly MOR202 at 8 mg/kg plus dexamethasone and lenalidomide. The other occurred in a patient receiving weekly MOR202 at 16 mg/kg plus dexamethasone.

“[T]he preliminary efficacy seen so far with MOR202 as single agent and in combinations is promising,” said investigator Marc-Steffen Raab, MD, of Heidelberg University Hospital and the German Cancer Research Center DKFZ in Heidelberg, Germany.

Safety

All 50 patients were evaluable for safety. Ninety-eight percent experienced an adverse event (AE), 66% of which were grade 3 or higher.

The most frequent AEs (overall and grade 3 or higher) were anemia (34%, 6%), leukopenia (30%, 10%), neutropenia (20%, 10%), thrombocytopenia (18%, 8%), fatigue (30%, 0%), nausea (22%, 0%), diarrhea (20%, 0%), and headache (16%, 0%).

Thirty-six percent of patients discontinued MOR202 due to treatment-emergent AEs. However, only 6% (n=3) of these AEs were considered possibly related to MOR202.

Infusion-related reactions occurred in 15 patients (30%). One of these patients received dexamethasone as well and experienced an infusion-related reaction (grade 1).

In the absence of dexamethasone, nearly all infusion reactions were grade 1-2. The exception was 1 patient with a grade 3 reaction that was mainly limited to the first infusion.

The maximum tolerated dose of MOR202 has not been reached.

“Considering the low rate of infusion reactions, even in cohorts without dexamethasone, the short infusion time, and other aspects, MOR202 may turn out to be an excellent choice in terms of safety and tolerability,” Dr Raab concluded.

Carfilzomib

Photo courtesy of Amgen

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion of the proteasome inhibitor carfilzomib (Kyprolis).

The CHMP is recommending the drug be approved for use in combination with lenalidomide and dexamethasone to treat adults with multiple myeloma (MM) who have received at least 1 prior therapy.

The CHMP’s positive opinion will be reviewed by the European Commission (EC).

The EC usually follows the CHMP’s recommendations and is expected to deliver its final decision within 3 months. The EC’s decision will apply to the 28 member countries of the European Union (EU), as well as Iceland, Lichtenstein, and Norway.

ASPIRE trial

The CHMP’s positive opinion of carfilzomib was based on data from the phase 3 ASPIRE trial, which were presented at ASH 2014 and published in NEJM.

The trial enrolled 792 patients with relapsed or refractory MM who had received 1 to 3 prior lines of therapy. The patients were randomized (1:1) to receive carfilzomib plus lenalidomide and dexamethasone (KRd) or just lenalidomide and dexamethasone (Rd) for 18 cycles.

Lenalidomide and dexamethasone were continued thereafter until disease progression. There was no planned cross-over from the control arm to treatment with carfilzomib.

The study’s primary endpoint was progression-free survival. And the median progression-free survival was significantly longer in the KRd arm than the Rd arm—26.3 months and 17.6 months, respectively (hazard ratio=0.69, P=0.0001).

At the time of analysis, the difference in overall survival did not reach the prespecified boundary for statistical significance.

The overall response rate was 87% in the KRd arm and 67% in the Rd arm. The median duration of response was 28.6 months and 21.2 months, respectively.

The rates of death due to adverse events (AEs) within 30 days of the last dose were similar between the treatment arms.

The most common causes of death not due to progressive disease occurring in patients in the KRd arm and the Rd arm, respectively, were cardiac disorders (3% vs 2%), infection (2% vs 3%), renal events (0% vs less than 1%), and other AEs (2% vs 3%).

Serious AEs were reported in 60% of the patients in the KRd arm and 54% in the Rd arm. The most common serious AEs reported in the KRd arm and the Rd arm, respectively, were pneumonia (14% vs 11%), respiratory tract infection (4% vs 2%), pyrexia (4% vs 2%), and pulmonary embolism (3% vs 2%).

Carfilzomib development

Carfilzomib was granted orphan drug designation in the EU in 2008. Last February, the drug’s application for EU approval was granted accelerated assessment.

Carfilzomib was approved as monotherapy in the US in July 2012 and in combination with lenalidomide and dexamethasone in July 2015. Carfilzomib is also approved for use in Argentina, Israel, Kuwait, Mexico, and Thailand.

Carfilzomib is a product of Onyx Pharmaceuticals, Inc., a subsidiary of Amgen that holds development and commercialization rights to the drug globally, excluding Japan. For more information on the drug, visit www.kyprolis.com.

Carfilzomib

Photo courtesy of Amgen

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion of the proteasome inhibitor carfilzomib (Kyprolis).

The CHMP is recommending the drug be approved for use in combination with lenalidomide and dexamethasone to treat adults with multiple myeloma (MM) who have received at least 1 prior therapy.

The CHMP’s positive opinion will be reviewed by the European Commission (EC).

The EC usually follows the CHMP’s recommendations and is expected to deliver its final decision within 3 months. The EC’s decision will apply to the 28 member countries of the European Union (EU), as well as Iceland, Lichtenstein, and Norway.

ASPIRE trial

The CHMP’s positive opinion of carfilzomib was based on data from the phase 3 ASPIRE trial, which were presented at ASH 2014 and published in NEJM.

The trial enrolled 792 patients with relapsed or refractory MM who had received 1 to 3 prior lines of therapy. The patients were randomized (1:1) to receive carfilzomib plus lenalidomide and dexamethasone (KRd) or just lenalidomide and dexamethasone (Rd) for 18 cycles.

Lenalidomide and dexamethasone were continued thereafter until disease progression. There was no planned cross-over from the control arm to treatment with carfilzomib.

The study’s primary endpoint was progression-free survival. And the median progression-free survival was significantly longer in the KRd arm than the Rd arm—26.3 months and 17.6 months, respectively (hazard ratio=0.69, P=0.0001).

At the time of analysis, the difference in overall survival did not reach the prespecified boundary for statistical significance.

The overall response rate was 87% in the KRd arm and 67% in the Rd arm. The median duration of response was 28.6 months and 21.2 months, respectively.

The rates of death due to adverse events (AEs) within 30 days of the last dose were similar between the treatment arms.

The most common causes of death not due to progressive disease occurring in patients in the KRd arm and the Rd arm, respectively, were cardiac disorders (3% vs 2%), infection (2% vs 3%), renal events (0% vs less than 1%), and other AEs (2% vs 3%).

Serious AEs were reported in 60% of the patients in the KRd arm and 54% in the Rd arm. The most common serious AEs reported in the KRd arm and the Rd arm, respectively, were pneumonia (14% vs 11%), respiratory tract infection (4% vs 2%), pyrexia (4% vs 2%), and pulmonary embolism (3% vs 2%).

Carfilzomib development

Carfilzomib was granted orphan drug designation in the EU in 2008. Last February, the drug’s application for EU approval was granted accelerated assessment.

Carfilzomib was approved as monotherapy in the US in July 2012 and in combination with lenalidomide and dexamethasone in July 2015. Carfilzomib is also approved for use in Argentina, Israel, Kuwait, Mexico, and Thailand.

Carfilzomib is a product of Onyx Pharmaceuticals, Inc., a subsidiary of Amgen that holds development and commercialization rights to the drug globally, excluding Japan. For more information on the drug, visit www.kyprolis.com.

Carfilzomib

Photo courtesy of Amgen

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion of the proteasome inhibitor carfilzomib (Kyprolis).

The CHMP is recommending the drug be approved for use in combination with lenalidomide and dexamethasone to treat adults with multiple myeloma (MM) who have received at least 1 prior therapy.

The CHMP’s positive opinion will be reviewed by the European Commission (EC).

The EC usually follows the CHMP’s recommendations and is expected to deliver its final decision within 3 months. The EC’s decision will apply to the 28 member countries of the European Union (EU), as well as Iceland, Lichtenstein, and Norway.

ASPIRE trial

The CHMP’s positive opinion of carfilzomib was based on data from the phase 3 ASPIRE trial, which were presented at ASH 2014 and published in NEJM.

The trial enrolled 792 patients with relapsed or refractory MM who had received 1 to 3 prior lines of therapy. The patients were randomized (1:1) to receive carfilzomib plus lenalidomide and dexamethasone (KRd) or just lenalidomide and dexamethasone (Rd) for 18 cycles.

Lenalidomide and dexamethasone were continued thereafter until disease progression. There was no planned cross-over from the control arm to treatment with carfilzomib.

The study’s primary endpoint was progression-free survival. And the median progression-free survival was significantly longer in the KRd arm than the Rd arm—26.3 months and 17.6 months, respectively (hazard ratio=0.69, P=0.0001).

At the time of analysis, the difference in overall survival did not reach the prespecified boundary for statistical significance.

The overall response rate was 87% in the KRd arm and 67% in the Rd arm. The median duration of response was 28.6 months and 21.2 months, respectively.

The rates of death due to adverse events (AEs) within 30 days of the last dose were similar between the treatment arms.

The most common causes of death not due to progressive disease occurring in patients in the KRd arm and the Rd arm, respectively, were cardiac disorders (3% vs 2%), infection (2% vs 3%), renal events (0% vs less than 1%), and other AEs (2% vs 3%).

Serious AEs were reported in 60% of the patients in the KRd arm and 54% in the Rd arm. The most common serious AEs reported in the KRd arm and the Rd arm, respectively, were pneumonia (14% vs 11%), respiratory tract infection (4% vs 2%), pyrexia (4% vs 2%), and pulmonary embolism (3% vs 2%).

Carfilzomib development

Carfilzomib was granted orphan drug designation in the EU in 2008. Last February, the drug’s application for EU approval was granted accelerated assessment.

Carfilzomib was approved as monotherapy in the US in July 2012 and in combination with lenalidomide and dexamethasone in July 2015. Carfilzomib is also approved for use in Argentina, Israel, Kuwait, Mexico, and Thailand.

Carfilzomib is a product of Onyx Pharmaceuticals, Inc., a subsidiary of Amgen that holds development and commercialization rights to the drug globally, excluding Japan. For more information on the drug, visit www.kyprolis.com.

Background: Pain due to bone metastases represents a common source of cancer-related morbidity. Not all patients who develop bone metastases develop pain. It is a subjective experience unique to each patient. We conducted a quality assessment project at the Providence VA Medical Center (PVAMC) to characterize the problem of pain due to bone metastases.

Methods: All veterans with bone metastases seen by the oncology service during 2011 to 2013 at the PVAMC were included. Pain scores were assessed from each outpatient visit. Scores ranged from 0 to10 with 0 to 3 considered mild pain, 4 to 6 moderate pain, and 7 to 10 severe pain. If veterans were found to have severe pain, then their charts were reviewed for the interventions undertaken and whether pain was brought to a more acceptable score.

Results: Sixty-nine veterans with bone metastases were included. Fifty-one percent experienced severe pain. Of those experiencing severe pain, 46% had lung cancer and 37% had prostate cancer. Ninety-four percent of veterans with lung cancer and bone metastases experienced severe pain. Of those veterans with severe pain, 94% were prescribed narcotics, 83% enrolled in hospice, 66% received palliative care, and 63% received radiation therapy. Eleven veterans in total were admitted to the hospital for pain control. It took a median of 25 days to reduce pain to a score of 3. Overall the median time from onset of severe pain to death was 80 days. For veterans with lung cancer, the median time to death was 63 days compared with 371 days in veterans with prostate cancer.

Conclusions: Many veterans with bone metastases experince severe pain. This project demonstrated that the majority of lung cancer patients reported extreme pain from their bone metastases, and the median time from severe pain onset to death was about 2 months. Early and aggressive pain control and palliative or hospice care may be particularly beneficial for these patients. In the future, we will seek to shorten the duration of time to adequate pain control through a quality improvement project.

Background: Pain due to bone metastases represents a common source of cancer-related morbidity. Not all patients who develop bone metastases develop pain. It is a subjective experience unique to each patient. We conducted a quality assessment project at the Providence VA Medical Center (PVAMC) to characterize the problem of pain due to bone metastases.

Methods: All veterans with bone metastases seen by the oncology service during 2011 to 2013 at the PVAMC were included. Pain scores were assessed from each outpatient visit. Scores ranged from 0 to10 with 0 to 3 considered mild pain, 4 to 6 moderate pain, and 7 to 10 severe pain. If veterans were found to have severe pain, then their charts were reviewed for the interventions undertaken and whether pain was brought to a more acceptable score.

Results: Sixty-nine veterans with bone metastases were included. Fifty-one percent experienced severe pain. Of those experiencing severe pain, 46% had lung cancer and 37% had prostate cancer. Ninety-four percent of veterans with lung cancer and bone metastases experienced severe pain. Of those veterans with severe pain, 94% were prescribed narcotics, 83% enrolled in hospice, 66% received palliative care, and 63% received radiation therapy. Eleven veterans in total were admitted to the hospital for pain control. It took a median of 25 days to reduce pain to a score of 3. Overall the median time from onset of severe pain to death was 80 days. For veterans with lung cancer, the median time to death was 63 days compared with 371 days in veterans with prostate cancer.

Conclusions: Many veterans with bone metastases experince severe pain. This project demonstrated that the majority of lung cancer patients reported extreme pain from their bone metastases, and the median time from severe pain onset to death was about 2 months. Early and aggressive pain control and palliative or hospice care may be particularly beneficial for these patients. In the future, we will seek to shorten the duration of time to adequate pain control through a quality improvement project.

Background: Pain due to bone metastases represents a common source of cancer-related morbidity. Not all patients who develop bone metastases develop pain. It is a subjective experience unique to each patient. We conducted a quality assessment project at the Providence VA Medical Center (PVAMC) to characterize the problem of pain due to bone metastases.

Methods: All veterans with bone metastases seen by the oncology service during 2011 to 2013 at the PVAMC were included. Pain scores were assessed from each outpatient visit. Scores ranged from 0 to10 with 0 to 3 considered mild pain, 4 to 6 moderate pain, and 7 to 10 severe pain. If veterans were found to have severe pain, then their charts were reviewed for the interventions undertaken and whether pain was brought to a more acceptable score.

Results: Sixty-nine veterans with bone metastases were included. Fifty-one percent experienced severe pain. Of those experiencing severe pain, 46% had lung cancer and 37% had prostate cancer. Ninety-four percent of veterans with lung cancer and bone metastases experienced severe pain. Of those veterans with severe pain, 94% were prescribed narcotics, 83% enrolled in hospice, 66% received palliative care, and 63% received radiation therapy. Eleven veterans in total were admitted to the hospital for pain control. It took a median of 25 days to reduce pain to a score of 3. Overall the median time from onset of severe pain to death was 80 days. For veterans with lung cancer, the median time to death was 63 days compared with 371 days in veterans with prostate cancer.

Conclusions: Many veterans with bone metastases experince severe pain. This project demonstrated that the majority of lung cancer patients reported extreme pain from their bone metastases, and the median time from severe pain onset to death was about 2 months. Early and aggressive pain control and palliative or hospice care may be particularly beneficial for these patients. In the future, we will seek to shorten the duration of time to adequate pain control through a quality improvement project.

Micrograph showing

multiple myeloma

The US Food and Drug Administration (FDA) has granted priority review for 4 drugs intended to treat multiple myeloma (MM): elotuzumab (Empliciti), daratumumab, ixazomib (MLN9708), and carfilzomib (Kyprolis).

The FDA grants priority review to investigational therapies that, if approved, may offer significant improvements in the treatment, prevention, or diagnosis of a serious condition.

The designation shortens the review period from 10 months to 6 months.

Carfilzomib

Carfilzomib, an injectable proteasome inhibitor, is currently under review for use in combination with dexamethasone to treat patients with relapsed MM who have received at least 1 prior therapy.

Carfilzomib is already FDA-approved for use in combination with lenalidomide and dexamethasone to treat patients with relapsed MM who have received 1 to 3 prior lines of therapy.

Carfilzomib also has accelerated approval from the FDA as monotherapy for MM patients who have received at least 2 prior therapies, including bortezomib and an immunomodulatory agent (IMiD), and have demonstrated disease progression on or within 60 days of completing their last treatment.

The new regulatory submission for carfilzomib is based on data from the phase 3 ENDEAVOR trial, which were presented at ASCO 2015. In this trial, relapsed MM patients who received carfilzomib and low-dose dexamethasone had significantly longer progression-free survival (PFS) than patients who received bortezomib and low-dose dexamethasone.

Carfilzomib is under development by Onyx Pharmaceuticals, Inc., an Amgen subsidiary.

Ixazomib

Ixazomib, an oral proteasome inhibitor, is under review for the treatment of relapsed and/or refractory MM. Ixazomib has orphan drug designation from the FDA for this patient population.

The regulatory submission for ixazomib is primarily based on results of the first interim analysis of the phase 3 TOURMALINE-MM1 trial.

In this trial, patients with relapsed and/or refractory MM who received ixazomib plus lenalidomide and dexamethasone had superior PFS to patients who received placebo plus lenalidomide and dexamethasone, according to Takeda Pharmaceutical Company Limited, the company developing ixazomib. Detailed data from this study have not yet been released.

Ixazomib is currently under investigation in 3 other phase 3 trials of MM patients:

• TOURMALINE-MM2, investigating ixazomib vs placebo, both in combination with lenalidomide and dexamethasone in patients with newly diagnosed MM
• TOURMALINE-MM3, investigating ixazomib vs placebo as maintenance therapy in patients with newly diagnosed MM following induction therapy and autologous stem cell transplant
• TOURMALINE-MM4, investigating ixazomib vs placebo as maintenance therapy in patients with newly diagnosed MM who have not undergone autologous stem cell transplant.

Daratumumab

Daratumumab, an investigational human anti-CD38 monoclonal antibody, is under review as monotherapy for MM patients who are refractory to both a proteasome inhibitor and an IMiD, or who have received 3 or more prior lines of therapy, including a proteasome inhibitor and an IMiD.

Daratumumab already has fast track, breakthrough therapy, and orphan drug designations from the FDA.

The regulatory submission for daratumumab is primarily supported by data from the phase 2 MMY2002 (SIRIUS) monotherapy study, which were presented at ASCO 2015. Results from this study indicated that daratumumab can produce responses in heavily pretreated MM patients.

Additional data from 4 other studies, including the phase 1/2 GEN501 monotherapy study, which was recently published in NEJM, also support the submission.

Daratumumab is under development by Janssen Research & Development, LLC.

Elotuzumab

Elotuzumab, a signaling lymphocyte activation molecule (SLAMF7)-directed immunostimulatory antibody, is under review for use in combination with lenalidomide and dexamethasone to treat MM patients who have received at least 1 prior treatment.

The FDA has already granted elotuzumab breakthrough therapy and orphan drug designations.

The regulatory submission for elotuzumab is primarily supported by data from the ELOQUENT-2 trial, which were presented at ASCO 2015. In this phase 3 study, researchers evaluated elotuzumab in combination with lenalidomide and dexamethasone, compared to lenalidomide and dexamethasone alone.

The submission is also supported by data from the CA204-009 trial, which were presented at EHA 2015. In this phase 2 study, researchers evaluated elotuzumab in combination with bortezomib and dexamethasone compared to bortezomib and dexamethasone alone.

Results from both trials suggested that adding elotuzumab to combination treatment can prolong PFS in MM patients.

Bristol-Myers Squibb and AbbVie are co-developing elotuzumab, with Bristol-Myers Squibb solely responsible for commercial activities.

Micrograph showing

multiple myeloma

The US Food and Drug Administration (FDA) has granted priority review for 4 drugs intended to treat multiple myeloma (MM): elotuzumab (Empliciti), daratumumab, ixazomib (MLN9708), and carfilzomib (Kyprolis).

The FDA grants priority review to investigational therapies that, if approved, may offer significant improvements in the treatment, prevention, or diagnosis of a serious condition.

The designation shortens the review period from 10 months to 6 months.

Carfilzomib

Carfilzomib, an injectable proteasome inhibitor, is currently under review for use in combination with dexamethasone to treat patients with relapsed MM who have received at least 1 prior therapy.

Carfilzomib is already FDA-approved for use in combination with lenalidomide and dexamethasone to treat patients with relapsed MM who have received 1 to 3 prior lines of therapy.

Carfilzomib also has accelerated approval from the FDA as monotherapy for MM patients who have received at least 2 prior therapies, including bortezomib and an immunomodulatory agent (IMiD), and have demonstrated disease progression on or within 60 days of completing their last treatment.

The new regulatory submission for carfilzomib is based on data from the phase 3 ENDEAVOR trial, which were presented at ASCO 2015. In this trial, relapsed MM patients who received carfilzomib and low-dose dexamethasone had significantly longer progression-free survival (PFS) than patients who received bortezomib and low-dose dexamethasone.

Carfilzomib is under development by Onyx Pharmaceuticals, Inc., an Amgen subsidiary.

Ixazomib

Ixazomib, an oral proteasome inhibitor, is under review for the treatment of relapsed and/or refractory MM. Ixazomib has orphan drug designation from the FDA for this patient population.

The regulatory submission for ixazomib is primarily based on results of the first interim analysis of the phase 3 TOURMALINE-MM1 trial.

In this trial, patients with relapsed and/or refractory MM who received ixazomib plus lenalidomide and dexamethasone had superior PFS to patients who received placebo plus lenalidomide and dexamethasone, according to Takeda Pharmaceutical Company Limited, the company developing ixazomib. Detailed data from this study have not yet been released.

Ixazomib is currently under investigation in 3 other phase 3 trials of MM patients:

• TOURMALINE-MM2, investigating ixazomib vs placebo, both in combination with lenalidomide and dexamethasone in patients with newly diagnosed MM
• TOURMALINE-MM3, investigating ixazomib vs placebo as maintenance therapy in patients with newly diagnosed MM following induction therapy and autologous stem cell transplant
• TOURMALINE-MM4, investigating ixazomib vs placebo as maintenance therapy in patients with newly diagnosed MM who have not undergone autologous stem cell transplant.

Daratumumab

Daratumumab, an investigational human anti-CD38 monoclonal antibody, is under review as monotherapy for MM patients who are refractory to both a proteasome inhibitor and an IMiD, or who have received 3 or more prior lines of therapy, including a proteasome inhibitor and an IMiD.

Daratumumab already has fast track, breakthrough therapy, and orphan drug designations from the FDA.

The regulatory submission for daratumumab is primarily supported by data from the phase 2 MMY2002 (SIRIUS) monotherapy study, which were presented at ASCO 2015. Results from this study indicated that daratumumab can produce responses in heavily pretreated MM patients.

Additional data from 4 other studies, including the phase 1/2 GEN501 monotherapy study, which was recently published in NEJM, also support the submission.

Daratumumab is under development by Janssen Research & Development, LLC.

Elotuzumab

Elotuzumab, a signaling lymphocyte activation molecule (SLAMF7)-directed immunostimulatory antibody, is under review for use in combination with lenalidomide and dexamethasone to treat MM patients who have received at least 1 prior treatment.

The FDA has already granted elotuzumab breakthrough therapy and orphan drug designations.

The regulatory submission for elotuzumab is primarily supported by data from the ELOQUENT-2 trial, which were presented at ASCO 2015. In this phase 3 study, researchers evaluated elotuzumab in combination with lenalidomide and dexamethasone, compared to lenalidomide and dexamethasone alone.

The submission is also supported by data from the CA204-009 trial, which were presented at EHA 2015. In this phase 2 study, researchers evaluated elotuzumab in combination with bortezomib and dexamethasone compared to bortezomib and dexamethasone alone.

Results from both trials suggested that adding elotuzumab to combination treatment can prolong PFS in MM patients.

Bristol-Myers Squibb and AbbVie are co-developing elotuzumab, with Bristol-Myers Squibb solely responsible for commercial activities.

Micrograph showing

multiple myeloma

The US Food and Drug Administration (FDA) has granted priority review for 4 drugs intended to treat multiple myeloma (MM): elotuzumab (Empliciti), daratumumab, ixazomib (MLN9708), and carfilzomib (Kyprolis).

The FDA grants priority review to investigational therapies that, if approved, may offer significant improvements in the treatment, prevention, or diagnosis of a serious condition.

The designation shortens the review period from 10 months to 6 months.

Carfilzomib

Carfilzomib, an injectable proteasome inhibitor, is currently under review for use in combination with dexamethasone to treat patients with relapsed MM who have received at least 1 prior therapy.

Carfilzomib is already FDA-approved for use in combination with lenalidomide and dexamethasone to treat patients with relapsed MM who have received 1 to 3 prior lines of therapy.

Carfilzomib also has accelerated approval from the FDA as monotherapy for MM patients who have received at least 2 prior therapies, including bortezomib and an immunomodulatory agent (IMiD), and have demonstrated disease progression on or within 60 days of completing their last treatment.

The new regulatory submission for carfilzomib is based on data from the phase 3 ENDEAVOR trial, which were presented at ASCO 2015. In this trial, relapsed MM patients who received carfilzomib and low-dose dexamethasone had significantly longer progression-free survival (PFS) than patients who received bortezomib and low-dose dexamethasone.

Carfilzomib is under development by Onyx Pharmaceuticals, Inc., an Amgen subsidiary.

Ixazomib

Ixazomib, an oral proteasome inhibitor, is under review for the treatment of relapsed and/or refractory MM. Ixazomib has orphan drug designation from the FDA for this patient population.

The regulatory submission for ixazomib is primarily based on results of the first interim analysis of the phase 3 TOURMALINE-MM1 trial.

In this trial, patients with relapsed and/or refractory MM who received ixazomib plus lenalidomide and dexamethasone had superior PFS to patients who received placebo plus lenalidomide and dexamethasone, according to Takeda Pharmaceutical Company Limited, the company developing ixazomib. Detailed data from this study have not yet been released.

Ixazomib is currently under investigation in 3 other phase 3 trials of MM patients:

• TOURMALINE-MM2, investigating ixazomib vs placebo, both in combination with lenalidomide and dexamethasone in patients with newly diagnosed MM
• TOURMALINE-MM3, investigating ixazomib vs placebo as maintenance therapy in patients with newly diagnosed MM following induction therapy and autologous stem cell transplant
• TOURMALINE-MM4, investigating ixazomib vs placebo as maintenance therapy in patients with newly diagnosed MM who have not undergone autologous stem cell transplant.

Daratumumab

Daratumumab, an investigational human anti-CD38 monoclonal antibody, is under review as monotherapy for MM patients who are refractory to both a proteasome inhibitor and an IMiD, or who have received 3 or more prior lines of therapy, including a proteasome inhibitor and an IMiD.

Daratumumab already has fast track, breakthrough therapy, and orphan drug designations from the FDA.

The regulatory submission for daratumumab is primarily supported by data from the phase 2 MMY2002 (SIRIUS) monotherapy study, which were presented at ASCO 2015. Results from this study indicated that daratumumab can produce responses in heavily pretreated MM patients.

Additional data from 4 other studies, including the phase 1/2 GEN501 monotherapy study, which was recently published in NEJM, also support the submission.

Daratumumab is under development by Janssen Research & Development, LLC.

Elotuzumab

Elotuzumab, a signaling lymphocyte activation molecule (SLAMF7)-directed immunostimulatory antibody, is under review for use in combination with lenalidomide and dexamethasone to treat MM patients who have received at least 1 prior treatment.

The FDA has already granted elotuzumab breakthrough therapy and orphan drug designations.

The regulatory submission for elotuzumab is primarily supported by data from the ELOQUENT-2 trial, which were presented at ASCO 2015. In this phase 3 study, researchers evaluated elotuzumab in combination with lenalidomide and dexamethasone, compared to lenalidomide and dexamethasone alone.

The submission is also supported by data from the CA204-009 trial, which were presented at EHA 2015. In this phase 2 study, researchers evaluated elotuzumab in combination with bortezomib and dexamethasone compared to bortezomib and dexamethasone alone.

Results from both trials suggested that adding elotuzumab to combination treatment can prolong PFS in MM patients.

Bristol-Myers Squibb and AbbVie are co-developing elotuzumab, with Bristol-Myers Squibb solely responsible for commercial activities.

Background: In addition to patient and/or family convenience, there is mounting category 1 evidence of the effectiveness of single fraction radiotherapy (SFRT) and its utility in the treatment of uncomplicated painful bone metastases. Surveys indicated that physicians in the U.S. still prefer multiple fractions radiotherapy (MFRT) for uncomplicated bone metastases compared with their Canadian or European colleagues. This report used code tracking to determine the scope of use of SFRT for painful malignant bone lesions compared with MFRT.

Methods: We reviewed encounters logged as international classification of disease (ICD) code 198.5 (secondary malignancy of bone and or bone marrow) and current procedural terminology (CPT) codes: 77427 (physician weekly visit for 3 to 5 treatments); and 77431 (physician weekly visit for 1 to 2 treatments) from 2002 to 2008 and 2009 to 2014.

Results: Data limitations/assumptions: The ICD 198.5 diagnosis code was pulled from either the primary or secondary position. By merging CPT/ICD codes to track use patterns, we noted a 43% increase in the use of SFRT for painful bone lesions at James J. Peters VA Medical Center. The CPT code 77431 was used on a yearly average of 2.45% of bone metastases cases from periods 2002 to 2008, and 5.67% (8.50% ex-cluding years 2009/2010) from 2009 to 2014. Of note, from the period years of 2003, 2008, and 2009 to 2010, CPT code 77431 was not used at all.

Conclusions: We saw an increased use of SFRT for bone metastases over the time period covered, and that tracking the encounters by ICD and CPT codes served, in part, as a useful tool in providing a snapshot view (if proper code is used) of SFRT usage. Physician education is a requisite for the proper use of CPT 77431 to capture the true rate of usage of SFRT in clinical practice.

Background: In addition to patient and/or family convenience, there is mounting category 1 evidence of the effectiveness of single fraction radiotherapy (SFRT) and its utility in the treatment of uncomplicated painful bone metastases. Surveys indicated that physicians in the U.S. still prefer multiple fractions radiotherapy (MFRT) for uncomplicated bone metastases compared with their Canadian or European colleagues. This report used code tracking to determine the scope of use of SFRT for painful malignant bone lesions compared with MFRT.

Methods: We reviewed encounters logged as international classification of disease (ICD) code 198.5 (secondary malignancy of bone and or bone marrow) and current procedural terminology (CPT) codes: 77427 (physician weekly visit for 3 to 5 treatments); and 77431 (physician weekly visit for 1 to 2 treatments) from 2002 to 2008 and 2009 to 2014.

Results: Data limitations/assumptions: The ICD 198.5 diagnosis code was pulled from either the primary or secondary position. By merging CPT/ICD codes to track use patterns, we noted a 43% increase in the use of SFRT for painful bone lesions at James J. Peters VA Medical Center. The CPT code 77431 was used on a yearly average of 2.45% of bone metastases cases from periods 2002 to 2008, and 5.67% (8.50% ex-cluding years 2009/2010) from 2009 to 2014. Of note, from the period years of 2003, 2008, and 2009 to 2010, CPT code 77431 was not used at all.

Conclusions: We saw an increased use of SFRT for bone metastases over the time period covered, and that tracking the encounters by ICD and CPT codes served, in part, as a useful tool in providing a snapshot view (if proper code is used) of SFRT usage. Physician education is a requisite for the proper use of CPT 77431 to capture the true rate of usage of SFRT in clinical practice.

Background: In addition to patient and/or family convenience, there is mounting category 1 evidence of the effectiveness of single fraction radiotherapy (SFRT) and its utility in the treatment of uncomplicated painful bone metastases. Surveys indicated that physicians in the U.S. still prefer multiple fractions radiotherapy (MFRT) for uncomplicated bone metastases compared with their Canadian or European colleagues. This report used code tracking to determine the scope of use of SFRT for painful malignant bone lesions compared with MFRT.

Methods: We reviewed encounters logged as international classification of disease (ICD) code 198.5 (secondary malignancy of bone and or bone marrow) and current procedural terminology (CPT) codes: 77427 (physician weekly visit for 3 to 5 treatments); and 77431 (physician weekly visit for 1 to 2 treatments) from 2002 to 2008 and 2009 to 2014.

Results: Data limitations/assumptions: The ICD 198.5 diagnosis code was pulled from either the primary or secondary position. By merging CPT/ICD codes to track use patterns, we noted a 43% increase in the use of SFRT for painful bone lesions at James J. Peters VA Medical Center. The CPT code 77431 was used on a yearly average of 2.45% of bone metastases cases from periods 2002 to 2008, and 5.67% (8.50% ex-cluding years 2009/2010) from 2009 to 2014. Of note, from the period years of 2003, 2008, and 2009 to 2010, CPT code 77431 was not used at all.

Conclusions: We saw an increased use of SFRT for bone metastases over the time period covered, and that tracking the encounters by ICD and CPT codes served, in part, as a useful tool in providing a snapshot view (if proper code is used) of SFRT usage. Physician education is a requisite for the proper use of CPT 77431 to capture the true rate of usage of SFRT in clinical practice.