P-185: Impact of the changing landscape of induction therapy prior to autologous stem cell transplantation in 540 myeloma patients: a retrospective real-world study

Abstract

<h3>Background</h3> High-dose therapy followed by autologous stem cell transplantation (ASCT) is the standard first line treatment for younger patients (pts) (<70 years) with multiple myeloma (MM). However, due to restrictive inclusion and exclusion criteria, more than half of MM pts were excluded from randomized phase 2/3 studies with ASCT. To overcome this and to better reflect clinical practice, we conducted a retrospective study to determine the efficacy and tolerability for all myeloma pts transplanted at the university hospital of Leipzig without trial-specific selection criteria. <h3>Methods</h3> This analysis included all consecutive pts with newly diagnosed MM who received first line induction therapy followed by high-dose therapy and ASCT between 1996 and 2019. <h3>Results</h3> 540 pts were enrolled in the study. The median age at diagnosis was 59 (range 29-75) years. In the first period up to 2005, induction therapy consisted mainly of conventional chemotherapies, e.g. vincristine/adriamycin/dexamethasone(VAD) (n=95). In the following years, the triple-combinations based on bortezomib coupled with anthracycline/dexamethasone (n=29), cyclophposphamide/dexamethasone (n=70) or bendamustine/prednisolone (n=169) became the most popular treatment options. After completion of induction therapy, the ORR in pts treated with VAD was only 66% with a ≥VGPR rate of 14% and ≥CR rate of 2%. The implementation of various bortezomib-containing therapy regimens significantly improved the ORR to 77-86% (p<0.005), with a ≥VGPR rate between 29-41% (p<0.001) and a ≥CR rate between 3-11% (p=0.07). 522 pts (96.7%) responded after the first ASCT with 75 sCR (13.8%), 40 CR (7.4%), 87 nCR (16.1%), 169 VGPR (31.3%) and 151 PR (28.0%). The ORR was no different following initial treatment with VAD (96%) or with bortezomib-containing therapies (97%). TRM was 0.6% (n=3). With the median follow-up of 45 months of the surviving pts, median PFS was 39 and median OS 79 months. Comparing the group of pts treated before 2006 with those treated after 2015, the use of the novel drugs improved the 48-months PFS from 33 to 47% and the 48-months OS from 61 to 85%. <h3>Conclusions</h3> The introduction post 2005 of modern three-drug induction regimens including bortezomib has improved the prognosis in younger MM pts undergoing first line ASCT. Our real world data in unselected pts also stress the substantial value of ASCT during the first line treatment of younger MM pts.