Adding Bortezomib and Bendamustine to High-Dose Melphalan in Autologous Haematopoietic Stem Cell Transplantation for...

High-dose melphalan (HDM) followed by autologous haematopoietic stem cell transplantation (ASCT) remains the standard of care for eligible patients with multiple myeloma (MM). Our objective was to evaluate the effectiveness and safety of adding bortezomib and bendamustine to melphalan (BBM) compared with HDM for relapsed MM, and investigate if BBM could offset the anticipated reduction in remission time observed after second ASCT (ASCT2) relative to first ASCT (ASCT1).

We conducted a retrospective analysis of medical records of 43 patients with relapsed MM who received BBM following first-line HDM from November 2011 to October 2018 at Uppsala University Hospital, and compared them with a cohort of 43 patients receiving HDM immediately before and after the BBM era.

The Kaplan-Meier estimated reduction in median time to next treatment was 26% for BBM- and 39% for HDM-treated patients in ASCT2 versus ASCT1 (p = 0.198), and 15% versus 39% in median progression-free survival (p = 0.0122). The estimated median overall survival after ASCT2 was 72.2 months versus 51.5 months (p = 0.14). Severe adverse events with BBM were consistent with those from HDM alone, although a trend toward increased risk of febrile neutropenia was observed.

Compared with standard HDM, the BBM-protocol in ASCT2 was associated with a smaller decline in progression-free survival relative to the ASCT1, and a consistent trend toward higher effectiveness across other measures. These findings suggest that BBM may help preserve efficacy in the setting of repeated transplantation and underscore the need for larger prospective studies to confirm these results.