Autologous stem cell transplantation plus RVd improves PFS in multiple myeloma  

Lenalidomide-bortezomib-dexamethasone (RVd) plus autologous stem cell transplantation (ASCT) delivered superior progression-free survival (PFS) in patients with newly diagnosed multiple myeloma compared with dexamethasone alone in the phase 3 DETERMINATION trial. However, no difference in overall survival (OS) was observed between the 2 regimens after 6 years of follow-up. 

The phase 3 DETERMINATION trial (NCT01208662) randomised patients with newly diagnosed multiple myeloma to RVd alone (n=357) or RVd plus ASCT (n=365). After the induction phase, ASCT, and consolidation therapy, all patients received lenalidomide maintenance therapy. The primary outcome measure was PFS. Prof. Paul Richardson (Harvard Medical School, MA, USA) presented the results [1].

The median PFS was significantly improved in patients who underwent ASCT in addition to RVd therapy compared with those who did not (67.5 vs 46.2 months; HR 1.53; P<0.0001). Interestingly, this effect appeared to be more pronounced in patients with international staging system (ISS) I disease (HR 1.83) than in patients with ISS II (HR 1.38) or ISS III disease (HR 1.14). Also, patients with a high cytogenetic risk benefitted relatively more from early ASCT (HR 1.99) than those with standard risk (HR 1.38). Another remarkable observed subgroup difference was that Black patients (20% of the included patients; HR 1.07) benefitted less from early ASCT than White patients (HR 1.67). Furthermore, a preliminary analysis of MRD status showed that a higher number of patients in the ASCT group reached MRD-negative status (54.4% vs 39.8%) and that MRD-negativity was associated with longer PFS, regardless of received treatment. Importantly, after a median follow-up of 76 months, OS was not improved in the ASCT arm compared with the control arm (80.7 vs 79.2 months; HR 1.10; P=0.99).

RVd plus ASCT was associated with higher but mostly manageable rates of toxicity. In total, 1.6% and 0.3% of the patients experienced fatal adverse events (AEs) in the ASCT plus RVd arm and RVd alone arm, respectively. In addition, grade ≥3 events (94.2% vs 78.2%) and haematologic grade ≥3 events (89.9% vs 60.5%) were more common in the combination arm.

“The PFS benefit with early ASCT in the first-line treatment of patients with multiple myeloma reaffirms ASCT as a standard-of-care. However, the similar OS results for both treatment arms supports the use of a personalised approach. Furthermore, we should investigate the impact of quadruplet therapies and perform whole-genome sequencing analyses to gain better insights in which patients should be selected for ASCT,” concluded Prof. Richardson.

1. Richardson PG, et al. Lenalidomide, bortezomib, anddexamethasone (RVd) ± autologous stem celltransplantation (ASCT) and R maintenance toprogressionfornewlydiagnosed multiple myeloma (NDMM): The phase 3 DETERMINATION trial. LBA4, ASCO 2022 Annual Meeting, 3–7 June, Chicago, IL, USA.

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Posted on 5 August 202218 March 2024