Description

Study design This is a retrospective single center cohort study comparing the new conditioning regimen bortezomib-bendamustine-melphalan to standard high-dose melphalan. The data sources will be electronic medical records and prospectively collected data from the Swedish Cancer Registry. The comparison will be analyzed in two parts. First, each patient will be its own control, comparing time to next treatment (TNT) for the first ASCT (always HDM, referred to as ASCT1) and second ASCT (BBM or HDM, referred to as ASCT2), and compare the mean difference between the two cohorts. Secondly, the difference in efficacy and severe adverse events between BBM and HDM at ASCT2 will be compared.

Study population Fifty consecutive patients, who were referred to Uppsala University Hospital (UUH) for a second ASCT after relapse in multiple myeloma following HDM and ASCT between 1 Nov 2011 and 30 Oct 2018 and who received conditioning with bortezomib-bendamustine-melphalan will be included in this study. As a control group, 25 consecutive patients who were treated with HDM prior to 1 Nov 2011 and 25 consecutive patients following 30 Oct 2018. The patients will be identified through the local European Society for Blood and Marrow Transplantation (EBMT) registry at UUH.

UUH is the referral hospital for seven Swedish regions with a total population of 2 151 353 at Dec 31 2022, which constitutes roughly one fifth of the population of Sweden.

Data collection Study data will be collected through systematic analysis of medical records from UUH and all the hospitals referring patients to UUH and from the Swedish Cancer Registry. All severe adverse events (AEs) will be collected until day 100 after ASCT2 according to National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) v5.0.

Primary endpoints

• Mean TNT after ASCT1 and ASCT2 for each individual patient (each patient as its own control), for BBM and HDM-treated patients

Secondary endpoints

• Median time to next treatment (TNT) after ASCT2
• Median progression free survival (PFS) after ASCT2
• Depth of best response (stable disease (SD), partial response (PR), very good partial response (VGPR), complete remission (CR), stringent complete remission (sCR)) after ASCT2
• Median Overall survival after ASCT2
• Treatment related mortality rate at ASCT2
• Mean duration of neutropenia (ANC < 0,5) at ASCT2
• Mean time until engraftment
• Mean duration of hospitalization after stem cell infusion at ASCT2
• The frequency of all serious adverse events according to version 5.0 of National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) during hospitalization and until day +100 after ASCT2.

Prespecified subgroups will include depth of best response prior to ASCT2, any specific maintenance therapies following ASCT2, patients receiving Granulocyte Colony Stimulating Factor (G-CSF) following ASCT, and patients receiving daratumumab as a part of induction or maintenance therapy at ASCT2.

In addition, an exploratory subgroup analysis is planned for patients with high-risk cytogenetics including p53-aberrations and patients with early relapse after ASCT1 (less than 3 years), although missing data is expected to be high.