DETERMINATION: Does one size fit all in multiple myeloma?

A subgroup analysis of the DETERMINATION trial, comparing lenalidomide, bortezomib, and dexamethasone (RVd) alone with RVd plus autologous stem cell transplant (ASCT) in patients with newly diagnosed multiple myeloma (MM), suggested that one size does not fit all. According to the authors, further studies are warranted to personalise therapy for patients.

The DETERMINATION trial (NCT01208662) randomised 729 newly diagnosed patients with MM (Black/African American 18.8%; White 76.4%) 1:1 to RVd alone or RVd plus ASCT [1]. The primary outcome of progression-free survival (PFS) showed that patients in the RVd plus ASCT arm had a significant benefit over patients in the control arm, with a median PFS of 67.5 months versus 46.2 months (HR 1.53; P<0.0001) [2]. “MM is a heterogeneous disease and newly diagnosed patients with MM are diverse,” Dr Hani Hassoun (Memorial Sloan Kettering Cancer Center, NY, USA) pointed out. “Therefore, we need to investigate whether one size fits all.” A subgroup analysis for PFS was performed to gain insights into this matter.

“Although most subgroups appeared to benefit from a transplant, some subgroups need to be considered,” continued Dr Hassoun. The benefit of transplant may be more apparent in White participants (HR 1.67; 95% CI 1.29–2.15) compared with Black/African American participants (HR 1.07; 95% CI 0.61–1.89). Also, those with a BMI <25 (HR 2.60; 95% CI 1.56–4.31) displayed a more pronounced advantage of transplant than those with a BMI between 25 and 30 (HR 1.24; 95% CI 0.86–1.80) or those with a BMI ≥30 (HR 1.41; 95% CI 0.98–0.02). Finally, patients with revised MM international staging system (R-ISS) III (HR 0.96; 95% CI 0.43–2.13) may have less benefit from transplant than those with R-ISS II (HR 1.63; 95% CI 1.22–2.19) or R-ISS I (HR 1.38; 95% CI 0.90–2.12). However, Dr Hassoun mentioned that R-ISS status and race were independent prognostic factors for PFS, favouring R-ISS I over R-ISS II and III in both arms and favouring Black over White in the RVd alone arm.

“We observed that there may be a differential impact of baseline prognostic factors on the treatment that is applied, potentially indicating differences in myeloma pathobiology within certain subgroups,” explained Dr Hassoun. “These data could help to differentiate patients who would benefit from ASCT, especially in the context of newer immunotherapies,” he decided.

1. Hassoun H, et al. Response rates and outcomes in newly diagnosed multiple myeloma patient subgroups receiving RVd + ASCT plus lenalidomide maintenance until progression in the phase 3 DETERMINATION trial. OS02-08, European Society for Blood and Marrow Transplantation (EBMT) 49^th Annual Meeting, 23–26 April 2023, Paris, France.
2. Richardson PG, et al. N Engl J Med 2022;387:132–147.

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Posted on 14 June 202315 February 2024