CHICAGO -- Isatuximab monotherapy showed efficacy in heavily pretreated multiple myeloma patients who had undergone a median of five previous lines of therapy, researchers reported here.
The investigational anti-CD38 antibody at a dose of 10 mg/kg led to 20% to 29% of patients achieving a response to treatment, and a median overall survival of 18.63 months, said of the John Theurer Cancer Center at Hackensack University Medical Center in New Jersey, and colleagues.
Action Points
- Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
- Isatuximab, an investigational anti-CD38 antibody, showed efficacy in heavily pretreated relapsed/recurrent multiple myeloma patients who had undergone a median of five previous lines of therapy.
- Note that the response rate and the duration of response with isatuximab was not dissimilar from that with daratumumab [Darzalex], a CD38-directed monoclonal antibody indicated for treatment of patients with multiple myeloma who have received at least three prior lines of therapy.
The phase II dose-finding study showed that patients receiving the 10 mg/kg dose every other week achieved the highest responses, Richter said in a presentation at the American Society of Clinical Oncology annual meeting.
"Isatuximab demonstrated single-agent activity in heavily pretreated patients with relapsed/recurrent multiple myeloma," he said.
Of the 74 patients in the highest dosing levels, 11 remain on treatment, Richter said. Of those who discontinued treatment, about 70% stopped due to disease progression, while six patients stopped due to adverse events. Progression-free survival among the patients taking at least 10 mg/kg of isatuximab was 3.65 months, he reported.
The patients treated in the study had been diagnosed with relapsed or recurrent multiple myeloma, and they were refractory to both immunomodulatory agents and proteasome inhibitors. Patients were also eligible to receive isatuximab if they had undergone treatment with three previous lines of therapy and had achieved at least a minor response to a previous treatment regimen.
The researchers tried four different doses of isatuximab, including a 3 mg/kg every other week dosing schedule that showed minor efficacy with 9% of patients achieving a response.
Patients treated with 10 mg/kg every other week for two cycles and then once every 4 weeks achieved a 20% overall response rate. It took 2 months to observe a response in patients at this dose; their best response occurred after 3 months of therapy.
Those treated with 10 mg/kg every other week achieved a 29% response rate. It took 0.9 months to observe a response in these patients, and it took 4.6 months to achieve the best response with this dose.
Patients treated with 20 mg/kg weekly for one cycle and than treatment every other week, achieved a 24% overall response, Richter reported. It took 1.35 months to see a response in this high-dose group and their best response was seen at that time.
Enrolled patients were about age 60, and had been diagnosed with multiple myeloma for 5 to 7 years before entering into the trial. About 30% of the patients were diagnosed with high-risk cytogenetics.
The majority had undergone autologous stem cell transplant, but the disease had recurred in these patients. More than 80% of the patients were diagnosed with double refractory disease and more than 40% appeared refractory to four agents, including lenalidomide (Revlimid), bortezomib (Velcade), pomalidomide (Pomalyst), and carfilzomib (Kyprolis).
Among the patients who were treated with at least 10 mg/kg of isatuximab, the overall response rate was 24.3%. Of the 13 patients ages 70 and up, 46.2% responded, while 36.4% of patients with kidney dysfunction responded. Also, 38.1% of patients with high-risk cytogenetics responded.
About 20%-25% of patients with previous treatments, or who were refractory to one drug or another, responded to treatment with isatuximab, the authors reported.
The most common adverse events were nausea, fatigue, and cough, but there were no grade 3 cases of these events. Pneumonia occurred in seven cases, and all of those were grade 3 or grade 4. Almost all patients experienced anemia and 24% of the cases were judged to be grade 3 or grade 4. Grade 3/4 thrombocytopenia was experienced by 17% of the patients, and grade 3/4 neutropenia was observed in 15% of the patients.
"Isatuximab is another CD38 antibody. I think the response rate and the duration of response was not dissimilar from what we see with daratumumab [Darzalex]," said of the Winship Cancer Center at Emory University in Atlanta. "Both drugs target the same antigen. It is interesting data, but I don't know if this is necessarily going to change treatment decisions."
"These drugs are very similar," Lonial, who was not involved in the study, told 乌鸦传媒. "I think they have trials designed to show value-added for their drug, we just haven't seen that yet. This is early data."
Disclosures
The trial was supported by Sanofi-Genzyme.
Richter disclosed relevant relationships with Amgen, Takeda, Janssen, Celgene and Novartis.
Lonial disclosed relevant relationships with Bristol-Myers Squibb, Celgene, Janssen Oncology, Millennium, Novartis, Onyx, and Sanofi.
Primary Source
American Society of Clinical Oncology
Richter J, et al "Updated data from a phase II dose finding trial of single agent isatuximab (SAR650984, anti-CD38 mAb) in relapsed/refractory multiple myeloma" ASCO 2016; Abstract 8005.