Real-world Data Highlight Daratumumab Compliance Rates in MM Patients

The anti-CD38 monoclonal antibody daratumumab (Darzalex) demonstrated a long duration with a high dosing compliance ratio according to data from a real-world analysis of patients with multiple myeloma (MM) presented at the 19th International Myeloma Society Annual Meeting.

Findings of a retrospective analysis of 2142 patients with MM showed that the median duration of treatment with daratumumab was 16.6 months. At 12, 24, and 36 months, 63.5% 33.1%, and 14.5% of patients remained on daratumumab, respectively.

Patients with a transplant post index date were censored and an additional subgroup analysis was conducted for patients (n = 1246) who had continuous insurance coverage for at least 12 months. Baseline characteristics were similar for the subgroup compared to the overall population, and median length of continuous daratumumab use was 24.7 months with 51.8% patients remaining on treatment at that time and nearly one-quarter of patients continuing past 3 years.

“Patients initiating daratumumab may continue to use it as a backbone of their treatment even if their line of therapy or treatment regimen changes,” Rafael Fonseca, MD, chief innovation officer at Mayo Clinic in Phoenix, Arizona said in a presentation of the data.

Continuous insurance coverage had a significant impact on how long patients remained on treatment. After 6 months 83.16% of the study sample remained on the therapy, while 99.91% of patients in the subgroup which had at least 12 months of continuous coverage remained on treatment; after 9 months, 72.55% vs 99.79% were on treatment and at 18 months 46.46% compared to 72.70% were on daratumumab, respectively.

The retrospective observational study was conducted using Optum’s deidentified Clinformatics Data Mart database leveraging patient records from November 1, 2015, to March 31, 2021. To be eligible, patients must have had continuous insurance coverage for at least 6 months or greater prior to baseline (24.2% had commercial, 75.8% had Medicare). Patients were excluded if they received a diagnosis of other types of malignancies, had a transplant, enrolled in a clinical trial, or received a diagnosis of light-chain amyloidosis.

“Duration of daratumumab treatment has been measured previously for each line of therapy; however, there has been a data gap since we do not know how long daratumumab is used continuously across multiple regimens or lines of therapy and the dosing frequency,” Fonseca said.

At baseline the median age of the patients was 70.9 years, with most patients (40%) being at least 75 years.

In the analysis, duration of use spanned over multiple lines of therapy and was defined as the time interval between first initiation and discontinuation of daratumumab. Dosing frequency was calculated as the average number of doses during defined time periods. The mean dosing frequency was consistent with the approved label and the dose compliance ratio was near 1.0 with the longer follow-up.

The approved label lists recommended dosages for daratumumab in the following groups: monotherapy and in combination with lenalidomide (Revlimid; D-Rd) or pomalidomide (Pomalyst; D-Pd) and dexamethasone; in combination with bortezomib (Velcade), melphalan, and prednisone (D-VMP); in combination with bortezomib, thalidomide (Thalomid), and dexamethasone (D-VTd); in combination with bortezomib and dexamethasone (D-Vd); and in combination with carfilzomib (Kyprolis) and dexamethasone (DKd). Dosage in all combinations was 16 mg/kg intravenous infusion, except for carfilzomib and dexamethasone (week one 8mg/kg with all following weeks being 16 mg/kg).

In a follow-up period ranging 0 to 12 months, the mean observed doses of daratumumab based on the D-Rd and D-Pd regimens was 22.0 vs the doses per label was 23, with a compliance ratio of 0.96. The follow-up period of 0 to 24 months showed a mean observed dose of 35.4 vs 36 daratumumab doses per label for a compliance ratio of 0.98.

Limitations of the study included the subgroup analysis which had the potential for immortal time bias. D-Rd was also approved in 2019 for patients with newly diagnosed MM making the follow-up period immature in the newly diagnosed group to fully estimate the duration of treatment.

“Overall, these results demonstrate that in myeloma patients receiving daratumumab treatment the duration of continued daratumumab use is long and the dosing compliance ratio is high,” Fonseca highlighted.

Reference

Fonseca R, Chinaeke E, Gupta N, Fu AZ, Ran T, Kaila S. Real-world duration of use and dosing frequency of daratumumab in patients with multiple myeloma in the U.S. Poster presented at: 19th International Myeloma Society Annual Meeting; August 25-27, 2022; Los Angeles, CA.