Daratumumab, a human CD38-directed monoclonal antibody, has been confirmed as safe in a population of heavily pretreated patients with multiple myeloma who received access to the treatment before the medication was commercially available, according to an early access treatment protocol study published in Cancer.
Daratumumab, a human CD38-directed monoclonal antibody, has been confirmed as safe in a population of heavily pretreated patients with multiple myeloma who received access to the treatment before the medication was commercially available, according to an early access treatment protocol (EAP) study published in Cancer.
“…EAPs offer an ethical, compliant means of addressing unmet needs in patients with limited treatment options, or who have exhausted all available options, by making a drug accessible to those who are not eligible for ongoing trials and before the drug is commercially available,” the authors explained.
The study included 348 patients with multiple myeloma who had received at least 3 lines of prior therapy, including a proteasome inhibitor or an immunomodulatory agent. In order to be included in the study, the patients must have lived in areas where daratumumab was not yet available commercially, must not have been enrolled in another daratumumab study, and either must not have been eligible for or had access to another ongoing clinical study.
The study collected additional safety information, as well as patient-reported outcome data using the European Organization for Research and Treatment of Cancer (EORTC) core quality-of-life questionnaire, the EORTC Multiple Myeloma Module, and the European Quality of Life 5 Dimensions Questionnaire. Assessments were collected at baseline, on day 1 of cycles 2, 3, 6, and then every other cycle, and at the end of the study.
The patients were given daratumumab 16 mg/kg weekly for 8 weeks, every other week for 16 weeks, and then monthly until their disease progressed, they experienced unacceptable toxicity, there was a loss of clinical benefit, or 60 days from when the drug gained US approval had passed.
Patients also received preinfusion and postinfusion medications, including acetaminophen, diphenhydramine, methylprednisolone, and montelukast to prevent infusion reactions (IRs). Studies that led to daratumumab’s approval had shown that IRs “were commonly characterized by symptoms similar to those of allergic rhinitis.” Since montelukast reduces asthma attacks and allergic rhinitis, it was allowed at the investigator’s discretion.
Half of patients experienced an IR at their first infusion, with rates declining sharply thereafter—by the second infusion, only 2% of patients experienced an IR. Commonly observed symptoms during IRs were cough, dyspnea, throat irritation, and nasal congestion. These were similar to previously described findings in studies that led to daratumumab’s US approval.
Only 50 patients received montelukast before the first infusion, and their IR rates were lower compared with patients who did not receive montelukast (38% vs 59%, respectively).
Overall, 65% (227) of patients experienced adverse events (AEs) related to daratumumab and only 85 patients (24%) experienced grade 3 and 4 AEs related to daratumumab. The most frequent daratumumab-related grade 3 and 4 AEs were thrombocytopenia (6%) and anemia (4%).
“In conclusion, this EAP study confirms the safety profile of daratumumab monotherapy in a large cohort of patients with relapsed and refractory [multiple myeloma] that was similar to the initial population indicated for daratumumab in the [United States],” the authors wrote.
Chari A, Lonial S, Mark TM, et al. Results of an early access treatment protocol of daratumumab in United States patients with relapsed or refractory multiple myeloma. [published online November 5, 2018]. Cancer. doi: 10.1002/cncr.31706.