Autologous stem cell transplantation plus RVd improves PFS in newly diagnosed multiple myeloma

Lenalidomide-bortezomib-dexamethasone (RVd) plus autologous stem cell transplantation (ASCT) delivered superior progression-free survival (PFS) to 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. Notably, approximately 20% of the included patients was African American. 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 months 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 may benefit relatively more from early ASCT (HR 1.99) than those with standard risk (HR 1.38). Another remarkable observed subgroup difference was that African American patients (HR 1.07) may benefit less from early ASCT than White/Caucasian 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 months 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.

1. Richardson PG, et al. Lenalidomide, bortezomib, and dexamethasone (RVd) ± autologous stem cell transplantation (ASCT) and R maintenance to progression for newly diagnosed 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 8 June, 20228 June, 2022