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Daratumumab monotherapy was associated with an overall response rate of 29.2% and was well tolerated in 106 heavily treated patients with multiple myeloma, based on results from the SIRIUS trial.
Of 106 patients who received daratumumab at 16 mg/kg, 3% achieved a stringent complete response, 9% had a very good partial response, and 17% had a partial response. The median progression-free survival was 3.7 months and median duration of response was 7.4 months. The 12-month overall survival was 64·8%, and, at a subsequent cutoff, median overall survival was 17.5 months.
All of the study patients had been treated with proteasome inhibitors and immunomodulatory drugs, with a median of five previous therapies. Most patients (80%) had received autologous stem cell transplantation, and 97% were refractory to the last line of therapy before study enrollment.
“Resistance to any previous therapy had no effect on the activity of daratumumab, lending support to a novel mechanism of action, but these findings need to be confirmed in larger studies,” wrote Dr. Sagar Lonial of Emory University, Atlanta, and colleagues (Lancet 2016;387:1551-60). Response rates were similar for patients with moderate renal impairment, those over age 75, and those with extramedullary disease or high-risk baseline cytogenetic characteristics.
Daratumumab was well tolerated, and none of the patients discontinued treatment because of treatment-related adverse events. The most common adverse events of any grade were anemia (33%), thrombocytopenia (25%), and neutropenia (23%). Additional supportive care in the form of red blood cell transfusions was received by 38% of patients, platelet transfusions by 13%, and granulocyte colony-stimulating factor by 8%. Fatigue (40%) and nausea (29%) were the most common nonhematologic adverse events. Serious adverse events were observed in 30% of patients.
Daratumumab compares favorably with other regimens such as pomalidomide alone or with dexamethasone or carfilzomib monotherapy, according to the investigators.
The favorable safety profile of daratumumab makes it an attractive candidate for combination regimens, the authors noted, and daratumumab combined with other backbone agents are currently under investigation.
This study was sponsored by Janssen, maker of daratumumab (Darzalex). Dr. Lonial reported consulting or advisory roles with Janssen and several other drug companies.
With its novel mechanism of action, single-agent activity, absence of crossresistance, and tolerability, daratumumab may prove to be a transformative new treatment for multiple myeloma.
 |
| Patrice Wendling/Frontline Medical News Dr. S. Vincent Rajkumar |
The single-agent activity of daratumumab (29%) exceeds that of bortezomib (27%), lenalidomide (26%), carfilzomib (24%), or pomalidomide (18%), even in a heavily pretreated population.
The safety profile is outstanding, and therein lies the reason for enthusiasm: Daratumumab can probably be combined with currently used triplet combinations in multiple myeloma, and can potentially take these highly active regimens to new heights.
Similar to rituximab, daratumumab will probably be added to many active triplet combinations. Daratumumab will likely move rapidly to a front-line setting in clinical trials for treatment of newly diagnosed multiple myeloma, maintenance therapy, and even smoldering multiple myeloma.
However, the data are insufficient to determine the cytogenetic subtypes that respond best to daratumumab. That information will be necessary in order to best sequence drugs according to the subtype of myeloma.
It will be important also to understand how daratumumab, an anti-CD38 drug, can work optimally with elotuzumab, another newly approved monoclonal antibody that targets SLAMF7.
Dr. S. Vincent Rajkumar is with the Mayo Clinic, Rochester, Minn. These remarks were part of an editorial (Lancet 2016; 387:1490-91) accompanying the study in the Lancet.
With its novel mechanism of action, single-agent activity, absence of crossresistance, and tolerability, daratumumab may prove to be a transformative new treatment for multiple myeloma.
|
| Patrice Wendling/Frontline Medical News Dr. S. Vincent Rajkumar |
The single-agent activity of daratumumab (29%) exceeds that of bortezomib (27%), lenalidomide (26%), carfilzomib (24%), or pomalidomide (18%), even in a heavily pretreated population.
The safety profile is outstanding, and therein lies the reason for enthusiasm: Daratumumab can probably be combined with currently used triplet combinations in multiple myeloma, and can potentially take these highly active regimens to new heights.
Similar to rituximab, daratumumab will probably be added to many active triplet combinations. Daratumumab will likely move rapidly to a front-line setting in clinical trials for treatment of newly diagnosed multiple myeloma, maintenance therapy, and even smoldering multiple myeloma.
However, the data are insufficient to determine the cytogenetic subtypes that respond best to daratumumab. That information will be necessary in order to best sequence drugs according to the subtype of myeloma.
It will be important also to understand how daratumumab, an anti-CD38 drug, can work optimally with elotuzumab, another newly approved monoclonal antibody that targets SLAMF7.
Dr. S. Vincent Rajkumar is with the Mayo Clinic, Rochester, Minn. These remarks were part of an editorial (Lancet 2016; 387:1490-91) accompanying the study in the Lancet.
With its novel mechanism of action, single-agent activity, absence of crossresistance, and tolerability, daratumumab may prove to be a transformative new treatment for multiple myeloma.
|
| Patrice Wendling/Frontline Medical News Dr. S. Vincent Rajkumar |
The single-agent activity of daratumumab (29%) exceeds that of bortezomib (27%), lenalidomide (26%), carfilzomib (24%), or pomalidomide (18%), even in a heavily pretreated population.
The safety profile is outstanding, and therein lies the reason for enthusiasm: Daratumumab can probably be combined with currently used triplet combinations in multiple myeloma, and can potentially take these highly active regimens to new heights.
Similar to rituximab, daratumumab will probably be added to many active triplet combinations. Daratumumab will likely move rapidly to a front-line setting in clinical trials for treatment of newly diagnosed multiple myeloma, maintenance therapy, and even smoldering multiple myeloma.
However, the data are insufficient to determine the cytogenetic subtypes that respond best to daratumumab. That information will be necessary in order to best sequence drugs according to the subtype of myeloma.
It will be important also to understand how daratumumab, an anti-CD38 drug, can work optimally with elotuzumab, another newly approved monoclonal antibody that targets SLAMF7.
Dr. S. Vincent Rajkumar is with the Mayo Clinic, Rochester, Minn. These remarks were part of an editorial (Lancet 2016; 387:1490-91) accompanying the study in the Lancet.
Daratumumab monotherapy was associated with an overall response rate of 29.2% and was well tolerated in 106 heavily treated patients with multiple myeloma, based on results from the SIRIUS trial.
Of 106 patients who received daratumumab at 16 mg/kg, 3% achieved a stringent complete response, 9% had a very good partial response, and 17% had a partial response. The median progression-free survival was 3.7 months and median duration of response was 7.4 months. The 12-month overall survival was 64·8%, and, at a subsequent cutoff, median overall survival was 17.5 months.
All of the study patients had been treated with proteasome inhibitors and immunomodulatory drugs, with a median of five previous therapies. Most patients (80%) had received autologous stem cell transplantation, and 97% were refractory to the last line of therapy before study enrollment.
“Resistance to any previous therapy had no effect on the activity of daratumumab, lending support to a novel mechanism of action, but these findings need to be confirmed in larger studies,” wrote Dr. Sagar Lonial of Emory University, Atlanta, and colleagues (Lancet 2016;387:1551-60). Response rates were similar for patients with moderate renal impairment, those over age 75, and those with extramedullary disease or high-risk baseline cytogenetic characteristics.
Daratumumab was well tolerated, and none of the patients discontinued treatment because of treatment-related adverse events. The most common adverse events of any grade were anemia (33%), thrombocytopenia (25%), and neutropenia (23%). Additional supportive care in the form of red blood cell transfusions was received by 38% of patients, platelet transfusions by 13%, and granulocyte colony-stimulating factor by 8%. Fatigue (40%) and nausea (29%) were the most common nonhematologic adverse events. Serious adverse events were observed in 30% of patients.
Daratumumab compares favorably with other regimens such as pomalidomide alone or with dexamethasone or carfilzomib monotherapy, according to the investigators.
The favorable safety profile of daratumumab makes it an attractive candidate for combination regimens, the authors noted, and daratumumab combined with other backbone agents are currently under investigation.
This study was sponsored by Janssen, maker of daratumumab (Darzalex). Dr. Lonial reported consulting or advisory roles with Janssen and several other drug companies.
Daratumumab monotherapy was associated with an overall response rate of 29.2% and was well tolerated in 106 heavily treated patients with multiple myeloma, based on results from the SIRIUS trial.
Of 106 patients who received daratumumab at 16 mg/kg, 3% achieved a stringent complete response, 9% had a very good partial response, and 17% had a partial response. The median progression-free survival was 3.7 months and median duration of response was 7.4 months. The 12-month overall survival was 64·8%, and, at a subsequent cutoff, median overall survival was 17.5 months.
All of the study patients had been treated with proteasome inhibitors and immunomodulatory drugs, with a median of five previous therapies. Most patients (80%) had received autologous stem cell transplantation, and 97% were refractory to the last line of therapy before study enrollment.
“Resistance to any previous therapy had no effect on the activity of daratumumab, lending support to a novel mechanism of action, but these findings need to be confirmed in larger studies,” wrote Dr. Sagar Lonial of Emory University, Atlanta, and colleagues (Lancet 2016;387:1551-60). Response rates were similar for patients with moderate renal impairment, those over age 75, and those with extramedullary disease or high-risk baseline cytogenetic characteristics.
Daratumumab was well tolerated, and none of the patients discontinued treatment because of treatment-related adverse events. The most common adverse events of any grade were anemia (33%), thrombocytopenia (25%), and neutropenia (23%). Additional supportive care in the form of red blood cell transfusions was received by 38% of patients, platelet transfusions by 13%, and granulocyte colony-stimulating factor by 8%. Fatigue (40%) and nausea (29%) were the most common nonhematologic adverse events. Serious adverse events were observed in 30% of patients.
Daratumumab compares favorably with other regimens such as pomalidomide alone or with dexamethasone or carfilzomib monotherapy, according to the investigators.
The favorable safety profile of daratumumab makes it an attractive candidate for combination regimens, the authors noted, and daratumumab combined with other backbone agents are currently under investigation.
This study was sponsored by Janssen, maker of daratumumab (Darzalex). Dr. Lonial reported consulting or advisory roles with Janssen and several other drug companies.
FROM THE LANCET
Key clinical point: Daratumumab was well tolerated and showed encouraging activity in heavily treated patients with multiple myeloma.
Major finding: In 106 patients previously treated with a median of five lines of therapy, the overall response rate to daratumumab at 16 mg/kg was 29.2%; 3% achieved a stringent complete response, 9% a very good partial response, and 17% a partial response.
Data sources: Data from the SIRIUS trial for 106 patients in the 16-mg/kg group.
Disclosures: This study was sponsored by Janssen, maker of daratumumab (Darzalex). Dr. Lonial reported consulting or advisory roles with Janssen and several other drug companies.
