Improved survival of multiple myeloma patients treated with autologous transplantation in the modern era of new medicine

Abstract

New drugs for multiple myeloma (MM) have dramatically improved patients' overall survival (OS). Autologous stem cell transplantation (ASCT) remains the mainstay for transplant-eligible MM patients. To investigate whether the post-ASCT prognosis of MM patients has been improved by new drugs, we undertook a retrospective observational analysis using the Transplant Registry Unified Management Program database in Japan. We analyzed 7323 patients (4135 men and 3188 women; median age, 59 years; range 16-77 years) who underwent upfront ASCT between January 2007 and December 2018. We categorized them by when they underwent ASCT according to the drugs' introduction in Japan: group 1 (2007-2010), group 2 (2011-2016), and group 3 (2017-2018). We compared the groups' post-ASCT OS. The 2-year OS rates (95% confidence interval [CI]) of groups 1, 2, and 3 were 85.8% (84.1%-87.4%), 89.1% (88.0%-90.1%), and 92.3% (90.0%-94.2%) (P < .0001) and the 5-year OS (95% CI) rates were 64.9% (62.4%-67.3%), 71.6% (69.7%-73.3%), and not applicable, respectively (P < .0001). A multivariate analysis showed that the post-ASCT OS was superior with these factors: age less than 65 years, performance status 0/1, low International Staging System (ISS) stage, receiving SCT for 180 days or less post-diagnosis, better treatment response pre-ASCT, later year of ASCT, and receiving SCT twice. A subgroup analysis showed poor prognoses for the patients with unfavorable karyotype and poor treatment response post-ASCT. The post-ASCT OS has thus improved over time (group 1 < 2 < 3) with the introduction of new drugs for MM. As the prognosis of high-risk-karyotype patients with ISS stage III remains poor, their treatment requires improvement.

Keywords: autologous stem cell transplantation; multiple myeloma; new medicine; overall survival; prognosis.

FIGURE 1

A, Overall survival (OS) from the time of autologous stem cell transplantation (ASCT) in Japanese patients with multiple myeloma (MM) who underwent ASCT in 2007‐2010 (group 1; black), 2011‐2016 (group 2; red), and 2017‐2018 (group 3; blue). B–D, OS of MM patients after ASCT by the International Staging System (ISS) stage at diagnosis: stage I (black), stage II (red), and stage III (blue). The number of patients at risk in each group is shown in the lower panel of each figure

FIGURE 2

Overall survival of Japanese patients with multiple myeloma after autologous stem cell transplantation (ASCT) according to treatment response before ASCT: complete response (CR; black), very good partial response (VGPR; red), partial response (PR; blue), and stable disease‐progressive disease (SD‐PD; green). (A) Group 1, ASCT in 2007‐2010. (B) Group 2, ASCT in 2011‐2016. (C) Group 3, ASCT in 2017‐2018

FIGURE 3

Overall survival of Japanese patients with multiple myeloma after autologous stem cell transplantation (ASCT) according to the type of cytogenic abnormality, ie, not‐unfavorable cytogenic abnormality (black) and unfavorable cytogenic abnormality (red) in (A) group 1, ASCT in 2007‐2010, (B) group 2, ASCT in 2011‐2013, and (C) group 3, ASCT in 2017‐2018

FIGURE 4

Impact of autologous stem cell transplantation (ASCT) on the overall survival of Japanese patients with multiple myeloma treated with new drugs. The effects of ASCT on each group are shown as forest plots. Diamonds on the lines indicate the hazard ratios (HR) for comparisons of (A) group 2 (ASCT in 2011‐2013) with group 1 (ASCT in 2007‐2010) and (B) group 3 (ASCT in 2017‐2018) with group 2. Horizontal lines indicate corresponding 95% confidence interval (CI). CR, complete response; ISS, International Staging System; PD, progressive disease; PR, partial response; PS, performance status; SD, stable disease; VGPR, very good partial response

FIGURE 5

Percentages of treatment response (A) before and (B) after autologous stem cell transplantation (ASCT) in Japanese patients with multiple myeloma according to the year of ASCT: group 1, 2007‐2010; group 2, 2011‐2016; and group 3, 2017‐2018. Treatment responses before and after ASCT were divided into four categories: complete response (CR; red), very good partial response (VGPR; blue), partial response (PR; green), and stable disease‐progressive disease (SD‐PD; yellow)