Novel antibody evokes responses in relapsed/refractory myeloma

CHICAGO – An investigational targeted therapy for multiple myeloma delayed disease progression in patients for whom as many as five prior lines of therapy had failed.

Daratumumab, an experimental antibody targeted to the CD38 receptor expressed at high levels on the surface of myeloma cells, was associated with a 29.2% overall response rate (ORR) at a median follow-up of 9.4 months, including three patients with a complete remission, said Dr. Saad Zafar Usmani of Levine Cancer Institute–Carolinas Healthcare System, Charlotte, N.C.

“Daratumumab monotherapy produced unprecedented overall responses that deepened over time in this heavily pretreated multiple myeloma patient population. These results highlight the potential of daratumumab as a novel, well-tolerated, single-agent therapy in various stages of myeloma treatment,” Dr. Usmani said at a briefing prior to the presentation of the data in a session at the annual meeting of the American Society of Clinical Oncology.

The results support further exploration of daratumumab in combination with currently available therapies for multiple myeloma, he added.

In the dose-selection portion of a phase II open-label, international, multicenter study, patients with multiple myeloma who had received at least three prior lines of therapy including a proteasome inhibitor and an immunomodulatory agent, or who had no treatment response to the most recent proteasome inhibitor and immunomodulator, were randomly assigned to receive either 8 mg/kg or 16 mg/kg daratumumab. After a response evaluation, the 16 mg/kg dose was chosen, and an additional 90 patients were enrolled at this dose.

As noted, the overall response rate, the primary endpoint, was 29.2%, consisting of three stringent complete responses, 10 very good partial responses, and 18 partial responses. The median duration of response was 7.4 months. The responses were consistent across all clinically relevant subgroups, Dr. Usmani said.

The median time to progression was 3.7 months. Median overall survival had not been reached at the time of the last data analysis, and the estimated 1-year overall survival rate was 65%.

At a median follow-up of 9.4 months, 14 of 31 patients with responses remained on therapy.

Patients tolerated the 16 mg/kg dose well, and none discontinued because of drug-related events.

Minor infusion site reactions (grade 1 or 2) were common during the first infusion and were managed with standard therapies, Dr. Usmani said.

“This is the first monoclonal antibody in myeloma that has shown single-agent activity,” Dr. Usmani said.

ASCO expert Dr. Merry-Jennifer Markham from the University of Florida in Gainesville, who was not involved in the study, commented that “there have been substantial treatment advances in multiple myeloma over the last decade, and daratumumab will be an important addition to the list of options. This therapy may offer a glimmer of hope for those myeloma patients who have run out of treatment options.

The study was funded by Janssen Research and Development. Dr. Usmani is on the speaker’s bureau for Janssen Oncology.

CHICAGO – An investigational targeted therapy for multiple myeloma delayed disease progression in patients for whom as many as five prior lines of therapy had failed.

Daratumumab, an experimental antibody targeted to the CD38 receptor expressed at high levels on the surface of myeloma cells, was associated with a 29.2% overall response rate (ORR) at a median follow-up of 9.4 months, including three patients with a complete remission, said Dr. Saad Zafar Usmani of Levine Cancer Institute–Carolinas Healthcare System, Charlotte, N.C.

“Daratumumab monotherapy produced unprecedented overall responses that deepened over time in this heavily pretreated multiple myeloma patient population. These results highlight the potential of daratumumab as a novel, well-tolerated, single-agent therapy in various stages of myeloma treatment,” Dr. Usmani said at a briefing prior to the presentation of the data in a session at the annual meeting of the American Society of Clinical Oncology.

The results support further exploration of daratumumab in combination with currently available therapies for multiple myeloma, he added.

In the dose-selection portion of a phase II open-label, international, multicenter study, patients with multiple myeloma who had received at least three prior lines of therapy including a proteasome inhibitor and an immunomodulatory agent, or who had no treatment response to the most recent proteasome inhibitor and immunomodulator, were randomly assigned to receive either 8 mg/kg or 16 mg/kg daratumumab. After a response evaluation, the 16 mg/kg dose was chosen, and an additional 90 patients were enrolled at this dose.

As noted, the overall response rate, the primary endpoint, was 29.2%, consisting of three stringent complete responses, 10 very good partial responses, and 18 partial responses. The median duration of response was 7.4 months. The responses were consistent across all clinically relevant subgroups, Dr. Usmani said.

The median time to progression was 3.7 months. Median overall survival had not been reached at the time of the last data analysis, and the estimated 1-year overall survival rate was 65%.

At a median follow-up of 9.4 months, 14 of 31 patients with responses remained on therapy.

Patients tolerated the 16 mg/kg dose well, and none discontinued because of drug-related events.

Minor infusion site reactions (grade 1 or 2) were common during the first infusion and were managed with standard therapies, Dr. Usmani said.

“This is the first monoclonal antibody in myeloma that has shown single-agent activity,” Dr. Usmani said.

ASCO expert Dr. Merry-Jennifer Markham from the University of Florida in Gainesville, who was not involved in the study, commented that “there have been substantial treatment advances in multiple myeloma over the last decade, and daratumumab will be an important addition to the list of options. This therapy may offer a glimmer of hope for those myeloma patients who have run out of treatment options.

The study was funded by Janssen Research and Development. Dr. Usmani is on the speaker’s bureau for Janssen Oncology.

CHICAGO – An investigational targeted therapy for multiple myeloma delayed disease progression in patients for whom as many as five prior lines of therapy had failed.

Daratumumab, an experimental antibody targeted to the CD38 receptor expressed at high levels on the surface of myeloma cells, was associated with a 29.2% overall response rate (ORR) at a median follow-up of 9.4 months, including three patients with a complete remission, said Dr. Saad Zafar Usmani of Levine Cancer Institute–Carolinas Healthcare System, Charlotte, N.C.

“Daratumumab monotherapy produced unprecedented overall responses that deepened over time in this heavily pretreated multiple myeloma patient population. These results highlight the potential of daratumumab as a novel, well-tolerated, single-agent therapy in various stages of myeloma treatment,” Dr. Usmani said at a briefing prior to the presentation of the data in a session at the annual meeting of the American Society of Clinical Oncology.

The results support further exploration of daratumumab in combination with currently available therapies for multiple myeloma, he added.

In the dose-selection portion of a phase II open-label, international, multicenter study, patients with multiple myeloma who had received at least three prior lines of therapy including a proteasome inhibitor and an immunomodulatory agent, or who had no treatment response to the most recent proteasome inhibitor and immunomodulator, were randomly assigned to receive either 8 mg/kg or 16 mg/kg daratumumab. After a response evaluation, the 16 mg/kg dose was chosen, and an additional 90 patients were enrolled at this dose.

As noted, the overall response rate, the primary endpoint, was 29.2%, consisting of three stringent complete responses, 10 very good partial responses, and 18 partial responses. The median duration of response was 7.4 months. The responses were consistent across all clinically relevant subgroups, Dr. Usmani said.

The median time to progression was 3.7 months. Median overall survival had not been reached at the time of the last data analysis, and the estimated 1-year overall survival rate was 65%.

At a median follow-up of 9.4 months, 14 of 31 patients with responses remained on therapy.

Patients tolerated the 16 mg/kg dose well, and none discontinued because of drug-related events.

Minor infusion site reactions (grade 1 or 2) were common during the first infusion and were managed with standard therapies, Dr. Usmani said.

“This is the first monoclonal antibody in myeloma that has shown single-agent activity,” Dr. Usmani said.

ASCO expert Dr. Merry-Jennifer Markham from the University of Florida in Gainesville, who was not involved in the study, commented that “there have been substantial treatment advances in multiple myeloma over the last decade, and daratumumab will be an important addition to the list of options. This therapy may offer a glimmer of hope for those myeloma patients who have run out of treatment options.

The study was funded by Janssen Research and Development. Dr. Usmani is on the speaker’s bureau for Janssen Oncology.