Daratumumab Retreatment Leads to Responses in Relapsed/Refractory Myeloma

Retreatment with daratumumab (Darzalex)-based regimens generated a similar overall response rate compared with initial treatment with a daratumumab-based regimen in patients with relapsed/refractory multiple myeloma, including those who were refractory to daratumumab, according to data from a retrospective study presented at the 2024 ASCO Annual Meeting.

The ORR in the initial daratumumab-based therapy arm (D1) was 52% vs 54% for the retreatment (D2) arm. Additional results in the D1 arm included 36% of patients having a partial response (PR), 13% having a very good partial response (VGPR), and 3% having a stringent complete response (sCR)/CR. In the D2 arm, 35% of patients had a PR, 13% had a VGPR, and 6% had a sCR/CR.

“In this retrospective study, [daratumumab] retreatment yielded response rates similar to ORR from initial daratumumab-based regimens despite a large proportion of patients being daratumumab refractor prior to D2,” Carlyn Rose Tan, MD, assistant attending physician at Memorial Sloan Kettering Cancer Center, and colleagues wrote in the poster.

According to the study authors, the use of daratumumab-containing regimens has increased in both newly diagnosed and relapsed/refractory multiple myeloma, which has prompted the need to understand the utility of retreating patients with these therapies. Additionally, prior research demonstrated that patients who receive daratumumab-based induction regimens may derive benefit from retreatment with the agent in subsequent lines of therapy.

A total of 157 patients were enrolled on the trial between January 1, 2015, and December 31, 2023. The last follow-up date was May 8, 2024. Of note, patients who had D1 treatment with newly diagnosed multiple myeloma were excluded from the trial. Additionally, responses were assessed per International Myeloma Working Group Response Criteria.

The median time between treatment of D1 and D2 was 239 days. Overall, 151 patients had daratumumab-refractory status, and at the beginning of D2, 118 were daratumumab refractory. The median time to next treatment for D2 was 8.94 months (95% CI, 6.44-12.0).

Overall, the median patient age was 67 years, 52% were male, 71% were White, 17% were Black, 6% were Asian, and 6% had unknown race. Based on the international staging system, 45% of patients had stage I disease, 39% had stage 2, and 16% had stage III. Of note, 67% of patients had standard cytogenetic risk, and 33% had high risk. The median number of lines of prior therapy at D1 was 2, and at D2, it was 4.

Between D1 and D2, 32% vs 4% of patients had daratumumab monotherapy, and 17% vs 27% had a proteasome inhibitor that included either bortezomib (Velcade), carfilzomib (Kyprolis), or ixazomib (Ninlaro). Between either arm, 45% vs 46% of patients also received daratumumab with an immunomodulatory agent, which included lenalidomide (Revlimid) or pomalidomide (Pomalyst).

The median PFS following daratumumab retreatment was 10.8 months (95% CI, 8.48-16.5), and the median follow-up was 53.9 months (95% CI, 48.3-60.1). The median overall survival was 47.4 months (95% CI, 41.5-not reached).

Subgroup analyses occurred for patients given 4 or fewer lines of therapy (n = 101) or more than 4 lines (n = 56) in the D2 arm. The median PFS was 16.53 months (95% CI, 9.66-23.3) vs 7.62 months (95% CI, 4.10-11.3) in patients who received fewer than 4 lines or more than 4 lines of therapy, respectively (P = .004).

For those with a retreatment interval of no more than 180 days, the median PFS was 16.1 months (95% CI, 9.03-29.4) vs 9.46 months (95% CI, 6.93-14.3) for more than 180 days (P = .11).

Reference

Tan CR, Rueda C, Shekarkhand T, et al. Clinical outcomes of retreatment with daratumumab-based regimens in anti-CD38 refractory multiple myeloma. J Clin Oncol. 2024;42(suppl 16):7570. doi:10.1200/JCO.2024.42.16_suppl.7570