Highlights in Multiple Myeloma

In this video, Dr Claudio Cerchione, Haematologist at the Istituto Romagnolo per lo Studio dei Tumori in Meldola, Italy shares his key take aways from ASH 2024 related to the management of multiple myeloma (MM).

During ASH 2024, several studies have generated evidence supporting the treatment of high-risk smoldering multiple myeloma (SMM). The most noteworthy of these studies consists of the phase III AQUILA trial. In this study, including 390 patients with high-risk SMM, 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 In addition to this, promising data were reported with the combination of carfilzomib, lenalidomide and dexamethasone and with ciltacabtagene autoleucel (cilta-cel) in patients with SMM.2,3

For patients with transplant-eligible MM, ASH 2024 featured an interesting update of the randomized, phase III GMMG HD-7 study.4 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.4

Moving to relapsed/refractory (RR) MM, ASH 2024 provided 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.5 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).5

Also in RRMM, very high rates of durable remissions were obtained with a combination of daratumumab and the new bispecific antibody ABBV-383 in a population of heavily pretreated patients.6 In the same setting, the phase Ib MagnetisMM-20 study demonstrated promising efficacy of the combination of elranatamab and carfilzomib-dexamethasone.7 Furthermore, different real-life studies including RRMM patients treated with elranatamab, teclistamab or CAR-T therapy demonstrate the feasibility of these treatment modalities outside of large academic centers. Finally, ASH 2024 confirmed the clinical potential of CELMoDs such as mezigdomide in patients with MM.8,9

In summary, the treatment landscape for patients with MM continues to evolve, with an ever-increasing list of potential treatment options across the different disease stages. With this growing number of therapeutic options, there is a need for biomarkers that allow for a better selection of the optimal treatment strategy for the individual patient.