Highlights in multiple myeloma

In this video, Prof Dr Michel Delforge, Haematologist at the University Hospitals Leuven (Leuven, Belgium) shares his key take aways from ASH 2024 related to the management of patients with multiple myeloma (MM).

The most noteworthy abstract in the field of smoldering multiple myeloma (SMM) discussed the results of the randomized phase III AQUILA study. In this trial, 390 patients with high-risk SMM were randomly assigned to receive daratumumab or undergo active monitoring.¹ After a median follow-up of 65.2 months, daratumumab proved to be associated with a 51% lower risk of disease progression or death compared to active monitoring (median PFS: not reached vs. 41.5 months; HR[95%CI]: 0.49[0.36-0.67]). Importantly, this delayed disease progression also translated into a significantly longer overall survival (OS) for patients in the daratumumab arm, with a 5 year OS rate of 93% for daratumumab as compared to 86.9% with active monitoring (HR[95%CI]: 0.52[0.27-0.98]).¹ As such, these findings provide a firm argument for physicians to treat patients with high-risk SMM, something that is currently not routine practice in Belgium.

For patients with transplant-eligible MM, ASH 2024 featured an interesting update of the randomized, phase III GMMG HD-7 study.² Previously, this trial demonstrated that the addition of isatuximab (Isa) to lenalidomide, bortezomib, and dexamethasone (RVd) significantly improved the rate of minimal residual disease (MRD) negativity at the end of induction therapy. At ASH 2024, PFS results for this study were presented, showing a significantly longer PFS for patients treated with Isa-RVd compared to RVd alone. This benefit was maintained after accounting for the second randomization in this trial (Isa-R or R maintenance) with a 3-year weighted PFS rate of 84% and 73% for Isa-RVd and RVd, respectively (HR[95%CI]: 0.63[0.38-1.07]).² A second presentation of this study confirmed the higher rate of MRD-negativity with Isa-RVd compared to RVd alone and demonstrated that this superiority was maintained over time.³

A second study in the transplant-eligible setting that was selected by Prof Delforge evaluated the possibility of stopping lenalidomide maintenance in patients with sustained MRD negativity.⁴ This study zoomed in on 51 patients who had at least 3 consecutive MRD negative results and had received at least 36 months of maintenance therapy with lenalidomide. Two years after stopping lenalidomide, 91.6% of these patients were still treatment free, dropping to 75.8% after three years. Importantly, most of the patients who did relapse in this study had high-risk features. As such, these findings suggest that treatment discontinuation may be feasible in patients without high-risk features who obtain a sustained MRD negativity under lenalidomide maintenance.⁴

In the transplant ineligible setting, results of the IMROZ trial showed that Isa-VRd followed by Isa-Rd led to a greater depth of response compared to VRd followed by Rd, with higher rates of MRD-negativity both at the end of induction and during the maintenance phase.⁵

Moving to relapsed/refractory (RR) MM, ASH 2024 featured updated results of the DREAMM-7 trial. This study compared the combination of belantamab mafodotin, bortezomib, and dexamethasone (BVd) to daratumumab, bortezomib, dexamethasone (DVd) in 494 MM patients with disease progression after ≥1 prior line of therapy.⁶ The study met its primary endpoint by showing a significantly longer PFS for patients treated with BVd compared to DVd (median: 36.6 vs. 13.4 months; HR[95%CI]: 0.41[0.31-0.53]; p< 0.00001). In addition, also the OS was significantly longer for BVd-treated patients compared to DVd, with 3-year OS rates of 74% and 60%, respectively HR[95%CI]: 0.58[0.43-0.79]; p= 0.00023).⁶

Other interesting abstracts on R/R MM assessed the optimal use of bispecific agents and CAR-T therapy, while others evaluated novel treatment modalities such as CELMoDs and bromodomain inhibitors. As such, ASH 2024 once again illustrated the rapidly changing treatment landscape in MM, opening new therapeutic avenues for patients across the entire disease course.