CHICAGO — Isatuximab monotherapy appeared active and generally well tolerated in patients with heavily pretreated relapsed, refractory multiple myeloma, according to updated results from a phase 2 dose-finding study presented at the ASCO Annual Meeting.
Isatuximab (SAR650984, Sanofi) is a humanized anti-CD38 monoclonal antibody with multiple modes of action for killing tumor cells through direct tumor targeting and immune cell engagement.
Joshua R. Richter, MD, a medical oncologist at Hackensack University Medical Center in New Jersey, and colleagues evaluated data from 97 patients (median age, 62.5 years; range, 38-85) with relapsed and/or refractory multiple myeloma. Patients were double refractory to an immunomodulatory agent and a proteasome inhibitor or had received at least three prior lines of therapy (median prior lines, 5; range, 2-14). Median time from diagnosis was 5.9 years.
Researchers noted 30% to 40% of patients were quadruple refractory to lenalidomide (Revlimid, Celgene), pomalidomide (Pomalyst, Celgene), bortezomib (Velcade, Takeda/Millennium) and carfilzomib (Kyprolis, Onyx) at baseline. In addition, a high number of patients had prior exposure to carfilzomib, of whom 50% were refractory to the therapy.
Researchers randomly assigned patients to isatuximab in one of four dosage arms: 3 mg/kg every 2 weeks, 10 mg/kg every 2 weeks for two cycles then every 4 weeks, 10 mg/kg every 2 weeks, or 20 mg/kg once weekly for four cycles then every 2 weeks.
Evaluation of isatuximab activity at these various doses served as the primary outcome measure.
Secondary outcomes included safety, tolerability, duration of response, PFS, OS and pharmacogenetics.
At the time of data cut-off in February, 11 patients remained on trial. Progressive disease was the primary reason for patient discontinuation.
Median dose duration was 16 weeks, and median follow-up was between 14 and 17 weeks.
Patients achieved a median OS of 18.63 months and median PFS of 3.65 months.
Overall response rate was 29% among those assigned 10 mg/kg isatuximab administered once every 2 weeks, 24% among those assigned 20 mg/kg once every 2 weeks, 20% for those assigned 10 mg/kg every 2 weeks then every 4 weeks, and 9% among those assigned 3 mg/kg every 2 weeks.
“Of note, the 20-mg/kg arm did not have as long as follow-up as those in the 10-mg/kg arms,” Richter said. “Something that we see now with this study, and essentially with all therapies in myeloma, is that patients who are able to stay on therapy longer tend to deepen their responses to treatment.”
Results of a subgroup analysis showed a 24.3% ORR for the two 10-mg/kg arms. Researchers observed impressive response rates specifically among higher-risk patients who were aged older, had poor renal function and high-risk cytogenetics.
“We find the data from subgroup analysis to be quite encouraging and hopefully, as more data mature, we will be able to confirm or at least get more information regarding this,” Richter said.
The most common adverse events included nausea (33%), fatigue (30%), dyspnea (26%) and cough (24%). Infusion-associated reactions occurred in 49% of patients, which were mostly grade 2 or lower. Ninety-four percent of these occurred during the first infusion. – by Jennifer Southall
Richter JR, et al. Abstract 8005. Presented at: ASCO Annual Meeting; June 3-7, 2016; Chicago.
Disclosure: Richter reports honoraria and speakers fees from and consultant roles with Amgen, Celgene, Janssen, Novartis and Takeda. Please see the abstract for a list of all other researchers’ relevant financial disclosures.