The impact of daratumumab pretreatment on multiple myeloma patients undergoing autologous transplantation

Abstract

The anti-CD38 antibody daratumumab (Dara) has been reported to improve the prognosis of multiple myeloma (MM) patients, but its use before autologous stem cell transplantation (ASCT) remains controversial. To clarify the prognostic impact of Dara before ASCT on MM, we performed a retrospective observational analysis. We analyzed 2626 patients who underwent ASCT between 2017 and 2020. In the comparison between patients not administered Dara (Dara- group) and those administered Dara (Dara+ group), the 1-year progression-free survival (PFS) rates were 87.4% and 77.3% and the 1-year overall survival (OS) rates were 96.7% and 90.0%, respectively. In multivariate analysis, age <65 years (p = 0.015), low international staging system (ISS) stage (p < 0.001), absence of unfavorable cytogenic abnormalities (p < 0.001), no Dara use before ASCT (p = 0.037), and good treatment response before ASCT (p < 0.001) were independently associated with superior PFS. In matched pair analysis, the PFS/OS of the Dara- group were also significantly superior. For MM patients who achieved complete or very good partial response (CR/VGPR) by Dara addition before ASCT, both PFS and OS significantly improved. However, in patients who did not achieve CR/VGPR before ASCT, the PFS/OS of the Dara+ group were significantly inferior to those of the Dara- group.

Keywords: autologous stem cell transplantation; daratumumab; multiple myeloma; prognosis; response.

FIGURE 1

(A, B) The PFS (A) and OS (B) from the time (months) of autologous stem cell transplantation (ASCT) of the daratumumab (Dara)– group (black) and the Dara+ group (red). The number of patients at risk in each group, 1‐year‐PFS or 1‐year‐OS with 95% confidence interval (CI) and median PFS (months) or OS (months) are shown in the lower panel of each figure. (C, D) The PFS (C) and OS (D) of the Dara– group (black) and Dara+ group (red) patients who obtained complete response (CR) or very good partial response (VGPR) response before ASCT were compared using a matched pair analysis. The number of patients at risk in each group, 1‐year‐PFS or 1‐year‐OS with 95% confidence interval (CI) are shown in the lower panel of each figure. (E, F) The PFS (E) and OS (F) of the Dara– group (black) and Dara+ group (red) who obtained only partial response (PR) or stable disease (SD) to progressive disease (PD) response before ASCT were compared using a matched pair analysis. The number of patients at risk in each group, 1‐year‐PFS or 1‐year‐OS with 95% confidence interval (CI) are shown in the lower panel of each figure.

FIGURE 2

(A) The proportion of the treatment response before autologous stem cell transplantation (ASCT) between the patients in the daratumumab (Dara)+ and Dara– group. (B, C) The proportion of the treatment response before ASCT between the patients who received ASCT within 6 months after the diagnosis and those who received ASCT 6 months or later after the diagnosis in the Dara+ group (B) and Dara– group (C). CR, complete remission; PD, progressive disease; PR, partial response; SD, stable disease; VGPR, very good partial response.

FIGURE 3

(A, B) The PFS (A) and OS (B) from the time of autologous stem cell transplantation (ASCT) of the daratumumab (Dara)– group (black) and the Dara+ group (red) patients who did not have unfavorable cytogenic abnormalities. The number of patients at risk in each group, 1‐year‐PFS or 1‐year‐OS with 95% confidence interval (CI) and median PFS (months) or OS (months) are shown in the lower panel of each figure. (C, D) The PFS (C) and OS (D) from the time of ASCT of the Dara– group (black) and the Dara+ group (red) patients who had unfavorable cytogenic abnormalities. The number of patients at risk in each group, 1‐year‐PFS or 1‐year‐OS with 95% confidence interval (CI) are shown in the lower panel of each figure.