Incorporating hematopoietic stem-cell transplantation after second-line carfilzomib-lenalidomide-dexamethasone (KRd)

Traditionally believed to be an integral part of multiple myeloma (MM) treatment, the role of hematopoietic stem-cell transplantation (HSCT) is being challenged. As such, we sought to evaluate the impact of HSCT in the era of novel agents.

A multicenter, retrospective, longitudinal cohort study was carried out between January 2016 and December 2018. A total of 55 patients who received VTD (bortezomib-thalidomide-dexamethasone) as first-line treatment and KRd (carfilzomib-lenalidomide-dexamethasone) as second-line treatment were analyzed for outcomes.

The enrolled patients were divided into Group 1, defined as those who continued KRd treatment until progression (n = 41), versus Group 2, defined as those who underwent HSCT after a certain number of cycles of KRd (n = 14). Both groups showed a generally favorable response to KRd, with overall response rate (ORR) of 87.9% and clinical benefit rate of 92.8% after a median of seven cycles in Group 1, and ORR 92.8% and clinical benefit rate 100% after median of five cycles in Group 2. However, significantly poorer progression-free survival (PFS) (p = 0.004) was observed in Group 1 (median 12 months) compared with Group 2 (median not reached). Multivariate analyses identified HSCT after KRd as potential risk factors associated with PFS. Also, in Group 1, bortezomib refractoriness was associated with significantly shorter PFS compared with those who were responsive (median 12 months versus 14 months, respectively, p = 0.039).

In conclusion, even with the advent of novel agents, HSCT still remains a valuable treatment modality with additive efficacy.