International Myeloma Workshop

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.

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.