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Daratumumab appears safe, effective in heavily pretreated multiple myeloma
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CHICAGO – The monoclonal antibody daratumumab yielded durable single-agent activity in patients with heavily treated multiple myeloma, according to the results of an ongoing phase 2 clinical trial presented at the ASCO Annual Meeting.
The agent also appeared safe, according to the researchers.
“Multiple myeloma is an incurable disease, and patients who relapse after treatment with proteasome inhibitors or immunotherapy drugs have poor prognoses and very few options,” Saad Zafar Usmani, MD, of the department of hematologic oncology at the Levine Cancer Institute at Carolina HealthCare Systems and a HemOnc Today Editorial Board member, said during a press conference. “CD-38 is highly expressed on multiple myeloma cells and is a promising therapeutic agent. Daratumumab … binds to CD-38–expressing cancer cells and induces cell death through multiple mechanisms.”
Saad Zafar Usmani
The FDA previously granted breakthrough therapy designation to daratumumab (Janssen R&D and Genmab) for the treatment of multiple myeloma, according to study background.
The researchers initially enrolled 34 patients with multiple myeloma in a two-part, open-label international study. All patients received three or more previous lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or were double refractory to a proteasome inhibitor and an immunomodulatory agent.
Patients received daratumumab in a dose of 8 mg/kg (n = 18) every 4 weeks or 16 mg/kg (n = 16) every week for 8 weeks, followed by every 2 weeks for 16 weeks and then every 4 weeks in order to determine the most effective dose.
The researchers then enrolled 90 additional patients to the 16-mg/kg dose daratumumab group. The current analysis includes data from the 106 patients treated on the 16-mg/kg dose arm. The median time since diagnosis for this cohort was 4.8 years, and patients had received a median of five prior treatment lines. Seventy-five percent of patients had an International Staging System score of 2 or higher.
Overall response rate (ORR) served as the primary endpoint.
Median follow-up was 9.4 months.
The ORR was 29.2%. Three patients experienced complete remission. Eighteen patients achieved partial response and 10 patients achieved very good partial response. The median duration of response was 7.4 months.
Researchers observed a median time to progression of 3.7 months.
Although median OS has not been reached, researchers estimate a 1-year OS rate of 65%.
The most common adverse events included fatigue (39.6%), anemia (33%), nausea (29.2%), thrombocytopenia (25.5%), back pain (22.6%), neutropenia (22.6%) and cough (20.8%). Forty-two percent of patients experienced infusion-related reactions, the majority of which were grade 1 or 2 and occurred during the first infusion.
Researchers reported that 45% of responding patients remained on therapy at follow-up. Five patients (4.7%) discontinued therapy due to adverse events; however, the researchers did not determined these events to be drug-related.
“These data support further studies of daratumumab in combination with the currently available and approved therapies,” Usmani said. – by Cameron Kelsall
For more information:
Lonial S, et al. Abstract LBA8512. Presented at: ASCO Annual Meeting; May 29-June 2, 2015; Chicago.
Disclosure: The study was funded by Janssen R&D. Usmani reports consultant and speakers bureau roles with Celgene, Millennium, Onyx and Sanofi and research funding from Array BioPharma, Celgene, Janssen R&D, Millennium and Onyx. Please see the full study for a list of all other researchers’ relevant financial disclosures.
Perspective
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Noopur Suresh Raje, MD
At the ASCO Annual Meeting we were all excited about this study by Lonial and colleagues on daratumumab (Janssen R&D and Genmab) as a single agent. We’re finally seeing monoclonal antibodies come to fruition, which I think is fantastic for myeloma. The daratumumab study included a little over 100 patients who were treated in an international trial. This was in patients who were essentially quadruple refractory, or refractory to lenalidomide (Revlimid, Celgene), pomalidomide (Pomalyst, Celgene), bortezomib (Velcade, Takeda) and carfilzomib (Kyprolis, Oynx). If you look at patients and survival of patients who are refractory to an immunomodulatory drug and a proteasome inhibitor, on average, their survival is pretty dismal — it’s less than 8 or 9 months. The PFS of these patients is very, very low — close to 5 months. What daratumumab has shown in this study of over 100 patients is a response rate of 30%. With this response rate, these responses have been fairly durable so that the PFS in these patients is close to 9 months and the median OS has not yet been reached. This is unprecedented. We have never seen a single agent monoclonal antibody work as well as it does in this very refractory population.
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