Monoclonal antibodies continue to show promise in treating multiple myeloma (MM), the third most prevalent blood cancer worldwide. Several Phase I-III studies targeting haematological malignancies were presented at the European Hematology Association Hybrid Congress 2024 (EHA 2024), highlighting the potential of new therapeutic options for both newly diagnosed and relapsed/refractory MM (RRMM).
DREAMM-8 Trial: Blenrep Combination Therapy
The Phase III DREAMM-8 trial evaluated the efficacy and safety of GSK’s Blenrep (belantamab) in combination with pomalidomide plus dexamethasone versus Bristol Myers Squibb’s Pomalyst/Imnovid (pomalidomide) plus bortezomib and dexamethasone for patients with RRMM who had undergone more than one prior line of therapy, including lenalidomide. After a median follow-up of 21.8 months, the median progression-free survival (PFS) was not reached for the Blenrep arm, compared to 12.7 months for the pomalidomide, bortezomib, and dexamethasone arm, with a hazard ratio (HR) of 0.52 (P<0.001). The 12-month PFS rates were 71% and 51%, respectively. The objective response rate (ORR) for the Blenrep arm was 77%, while it was 72% for the comparator arm. The complete response (CR) rate was 40% in the Blenrep arm versus 16% in the comparator arm. While a favorable trend in overall survival (OS) (HR 0.77) was observed, follow-up is ongoing. Adverse events (AEs) occurred in over 99% of patients receiving Blenrep (91% grade 3/4) and 96% of patients in the comparator arm (73% grade 3/4). Ocular AEs were reported in 89% of Blenrep patients (43% grade 3/4), while only 30% of comparator arm patients experienced them (2% grade 3/4). Serious adverse events (SAEs) occurred in 63% and 45% of patients, respectively. Fatal SAEs occurred in 11% of both groups. The treatment discontinuation rate due to AEs was 15% in the Blenrep arm and 12% in the comparator arm. These results, combined with those from the Phase III DREAMM-7 trial, suggest that this combination treatment will become a new option for individuals after a first relapse or those heavily pre-treated for MM.
LINKER-MM1 Study: Linvoseltamab Monotherapy
Data from the Phase I/II first-in-human, open-label LINKER-MM1 study, which investigated the safety, tolerability, and anti-tumour activity of Regeneron's linvoseltamab monotherapy as a treatment for RRMM, were also presented. Linvoseltamab exhibited substantial efficacy in RRMM patients during a median follow-up of 14.3 months for 117 patients in the 200 mg dosing cohorts. The ORR was 71%, with partial response (≥VGPR) at 65% and a CR or greater at 50%. The median duration of response (DOR) was 29.4 months, with a 12-month likelihood of maintaining response of 81% for all responders. The 12-month PFS was 70% for all patients and 96.3% for those with CR. The 12-month OS was 75% for all patients and 100% for those with CR. Cytokine release syndrome (46.2%), neutropenia (42.7%), and anemia (38.5%) were the most frequently reported treatment-emergent adverse events. The FDA has granted linvoseltamab Fast Track designation and accepted it for priority review for RRMM treatment, with a decision expected by August 22, 2024. Regulatory MAA applications are also under review by the EMA.
GMMG-HD7 Trial: Sarclisa in Newly Diagnosed MM
The interim analysis of the Phase III GMMG-HD7 trial evaluated the addition of Sanofi's Sarclisa (isatuximab) to standard-of-care induction (lenalidomide, bortezomib, and dexamethasone; RVd) followed by high-dose therapy (HDT) and autologous stem cell transplantation (ASCT). The trial, which included 662 patients, demonstrated that the Sarclisa and RVd therapy combination arm (Isa-RVd) had significantly deeper responses and higher rates of minimal residual disease (MRD) negativity than the RVd arm. Specifically, the Isa-RVd arm exhibited higher rates of CR or better (43.5% versus 34.0%) and VGPR (82.8% versus 68.7%). Furthermore, 66.2% of patients in the Isa-RVd arm attained MRD negativity following the most recent ASCT, compared to 47.7% in the RVd arm. After intensification, MRD negativity rates remained higher for Isa-RVd (72.0% versus 56.5%). In the BENEFIT trial, Sarclisa increased MRD negativity to 47%, compared to 24% in patients treated with lenalidomide and dexamethasone (Rd) in transplant-ineligible newly diagnosed MM patients. The FDA has also accepted a priority review for this combination regimen for transplant-ineligible treatment-naïve MM patients, with an expected outcome by 2024.
