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© ASCO/Todd Buchanan
Single-agent daratumumab has exhibited “encouraging efficacy” and a “favorable safety profile” in patients with heavily pretreated and refractory multiple myeloma (MM), according to investigators from the phase 2 SIRIUS trial.
The drug produced an overall response rate of 30% in MM patients who had received 3 or more prior lines of therapy. The median progression-free survival was close to 4 months, and the median overall survival was nearly 18 months.
Thirty percent of patients had treatment-emergent serious adverse events (AEs), and 23% had grade 3 or 4 treatment-emergent serious AEs.
“This represents the first single-agent activity we have for a monoclonal antibody in treating multiple myeloma,” said study author Sagar Lonial, MD, of Emory University School of Medicine in Atlanta, Georgia.
“The future hope for daratumumab is in our ability to bring this active agent to earlier lines of therapy and combine it with drugs where you may get synergy.”
Dr Lonial and his colleagues reported results from the ongoing SIRIUS trial in The Lancet. Results from the trial were previously presented at the 2015 ASCO Annual Meeting. The research was funded by Janssen Research & Development, the company developing daratumumab.
In part 1 of the trial, 34 MM patients were randomized to receive either 8 mg/kg of daratumumab once every 4 weeks or 16 mg/kg once a week for 8 weeks, then once every 2 weeks for 16 weeks and once every 4 weeks after that, until disease progression or unacceptable toxicity.
In part 2, an additional 90 MM patients were enrolled and received 16 mg/kg of daratumumab on the same dosing schedule as in part 1.
Dr Lonial and his colleagues reported results for all patients who received 16 mg/kg of daratumumab. At the first interim analysis, the 8 mg/kg arm did not meet the criteria for expansion because the overall response rate was 11.1%.
The 106 patients who received the 16 mg/kg dose of daratumumab had received a median of 5 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory drug. Ninety-seven percent of these patients were refractory to their last line of therapy, and 95% were refractory to both a proteasome inhibitor and an immunomodulatory drug.
Response and survival
According to an independent review committee, 29.2% of patients responded to daratumumab. Eighteen patients had a partial response, 10 had a very good partial response, and 3 had a stringent complete response.
The median duration of response was 7.4 months, and the median time to first response was 1 month.
The median overall survival was 17.5 months, and the 12-month overall survival was 64.8%. The median progression-free survival was 3.7 months.
Safety
The most common AEs were fatigue (40%), anemia (33%), nausea (29%), thrombocytopenia (25%), neutropenia (23%), back pain (22%), and cough (21%). Thirty percent of patients experienced serious AEs, and 23% had serious grade 3/4 AEs.
Infusion-related reactions were reported in 42% of patients and were predominantly grade 1 or 2 (5% grade 3; no grade 4). The most common infusion-related reactions were nasal congestion (12%), throat irritation (7%), cough (6%), dyspnea (6%), chills (6%), and vomiting (6%)—all of which were treated with standard of care and slower infusion rates.
None of the patients discontinued daratumumab because of drug-related treatment-emergent AEs, infusion-related reactions, or death. However, 5% of patients discontinued treatment because of treatment-emergent AEs—2 cases of progressive disease and 1 case each of H1N1 influenza, hypercalcemia, and spinal cord compression.
Twenty-nine percent of patients died after treatment—27% due to progressive disease and 2% due to AEs. The 2 AEs were cardiorespiratory failure secondary to H1N1 influenza complications and general health deterioration secondary to complications of aspiration pneumonia. 
© ASCO/Todd Buchanan
Single-agent daratumumab has exhibited “encouraging efficacy” and a “favorable safety profile” in patients with heavily pretreated and refractory multiple myeloma (MM), according to investigators from the phase 2 SIRIUS trial.
The drug produced an overall response rate of 30% in MM patients who had received 3 or more prior lines of therapy. The median progression-free survival was close to 4 months, and the median overall survival was nearly 18 months.
Thirty percent of patients had treatment-emergent serious adverse events (AEs), and 23% had grade 3 or 4 treatment-emergent serious AEs.
“This represents the first single-agent activity we have for a monoclonal antibody in treating multiple myeloma,” said study author Sagar Lonial, MD, of Emory University School of Medicine in Atlanta, Georgia.
“The future hope for daratumumab is in our ability to bring this active agent to earlier lines of therapy and combine it with drugs where you may get synergy.”
Dr Lonial and his colleagues reported results from the ongoing SIRIUS trial in The Lancet. Results from the trial were previously presented at the 2015 ASCO Annual Meeting. The research was funded by Janssen Research & Development, the company developing daratumumab.
In part 1 of the trial, 34 MM patients were randomized to receive either 8 mg/kg of daratumumab once every 4 weeks or 16 mg/kg once a week for 8 weeks, then once every 2 weeks for 16 weeks and once every 4 weeks after that, until disease progression or unacceptable toxicity.
In part 2, an additional 90 MM patients were enrolled and received 16 mg/kg of daratumumab on the same dosing schedule as in part 1.
Dr Lonial and his colleagues reported results for all patients who received 16 mg/kg of daratumumab. At the first interim analysis, the 8 mg/kg arm did not meet the criteria for expansion because the overall response rate was 11.1%.
The 106 patients who received the 16 mg/kg dose of daratumumab had received a median of 5 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory drug. Ninety-seven percent of these patients were refractory to their last line of therapy, and 95% were refractory to both a proteasome inhibitor and an immunomodulatory drug.
Response and survival
According to an independent review committee, 29.2% of patients responded to daratumumab. Eighteen patients had a partial response, 10 had a very good partial response, and 3 had a stringent complete response.
The median duration of response was 7.4 months, and the median time to first response was 1 month.
The median overall survival was 17.5 months, and the 12-month overall survival was 64.8%. The median progression-free survival was 3.7 months.
Safety
The most common AEs were fatigue (40%), anemia (33%), nausea (29%), thrombocytopenia (25%), neutropenia (23%), back pain (22%), and cough (21%). Thirty percent of patients experienced serious AEs, and 23% had serious grade 3/4 AEs.
Infusion-related reactions were reported in 42% of patients and were predominantly grade 1 or 2 (5% grade 3; no grade 4). The most common infusion-related reactions were nasal congestion (12%), throat irritation (7%), cough (6%), dyspnea (6%), chills (6%), and vomiting (6%)—all of which were treated with standard of care and slower infusion rates.
None of the patients discontinued daratumumab because of drug-related treatment-emergent AEs, infusion-related reactions, or death. However, 5% of patients discontinued treatment because of treatment-emergent AEs—2 cases of progressive disease and 1 case each of H1N1 influenza, hypercalcemia, and spinal cord compression.
Twenty-nine percent of patients died after treatment—27% due to progressive disease and 2% due to AEs. The 2 AEs were cardiorespiratory failure secondary to H1N1 influenza complications and general health deterioration secondary to complications of aspiration pneumonia.
© ASCO/Todd Buchanan
Single-agent daratumumab has exhibited “encouraging efficacy” and a “favorable safety profile” in patients with heavily pretreated and refractory multiple myeloma (MM), according to investigators from the phase 2 SIRIUS trial.
The drug produced an overall response rate of 30% in MM patients who had received 3 or more prior lines of therapy. The median progression-free survival was close to 4 months, and the median overall survival was nearly 18 months.
Thirty percent of patients had treatment-emergent serious adverse events (AEs), and 23% had grade 3 or 4 treatment-emergent serious AEs.
“This represents the first single-agent activity we have for a monoclonal antibody in treating multiple myeloma,” said study author Sagar Lonial, MD, of Emory University School of Medicine in Atlanta, Georgia.
“The future hope for daratumumab is in our ability to bring this active agent to earlier lines of therapy and combine it with drugs where you may get synergy.”
Dr Lonial and his colleagues reported results from the ongoing SIRIUS trial in The Lancet. Results from the trial were previously presented at the 2015 ASCO Annual Meeting. The research was funded by Janssen Research & Development, the company developing daratumumab.
In part 1 of the trial, 34 MM patients were randomized to receive either 8 mg/kg of daratumumab once every 4 weeks or 16 mg/kg once a week for 8 weeks, then once every 2 weeks for 16 weeks and once every 4 weeks after that, until disease progression or unacceptable toxicity.
In part 2, an additional 90 MM patients were enrolled and received 16 mg/kg of daratumumab on the same dosing schedule as in part 1.
Dr Lonial and his colleagues reported results for all patients who received 16 mg/kg of daratumumab. At the first interim analysis, the 8 mg/kg arm did not meet the criteria for expansion because the overall response rate was 11.1%.
The 106 patients who received the 16 mg/kg dose of daratumumab had received a median of 5 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory drug. Ninety-seven percent of these patients were refractory to their last line of therapy, and 95% were refractory to both a proteasome inhibitor and an immunomodulatory drug.
Response and survival
According to an independent review committee, 29.2% of patients responded to daratumumab. Eighteen patients had a partial response, 10 had a very good partial response, and 3 had a stringent complete response.
The median duration of response was 7.4 months, and the median time to first response was 1 month.
The median overall survival was 17.5 months, and the 12-month overall survival was 64.8%. The median progression-free survival was 3.7 months.
Safety
The most common AEs were fatigue (40%), anemia (33%), nausea (29%), thrombocytopenia (25%), neutropenia (23%), back pain (22%), and cough (21%). Thirty percent of patients experienced serious AEs, and 23% had serious grade 3/4 AEs.
Infusion-related reactions were reported in 42% of patients and were predominantly grade 1 or 2 (5% grade 3; no grade 4). The most common infusion-related reactions were nasal congestion (12%), throat irritation (7%), cough (6%), dyspnea (6%), chills (6%), and vomiting (6%)—all of which were treated with standard of care and slower infusion rates.
None of the patients discontinued daratumumab because of drug-related treatment-emergent AEs, infusion-related reactions, or death. However, 5% of patients discontinued treatment because of treatment-emergent AEs—2 cases of progressive disease and 1 case each of H1N1 influenza, hypercalcemia, and spinal cord compression.
Twenty-nine percent of patients died after treatment—27% due to progressive disease and 2% due to AEs. The 2 AEs were cardiorespiratory failure secondary to H1N1 influenza complications and general health deterioration secondary to complications of aspiration pneumonia.