EHA 2024: Monoclonal Antibodies Show Promise in Multiple Myeloma Treatment
Key Insights
The DREAMM-8 trial demonstrated that Blenrep combined with pomalidomide and dexamethasone significantly improved progression-free survival in relapsed/refractory multiple myeloma (search) (RRMM) patients compared to pomalidomide, bortezomib, and dexamethasone.
Linvoseltamab monotherapy in the LINKER-MM1 study showed substantial efficacy in RRMM patients, with a high objective response rate and durable responses, marking it as a promising treatment option.
The GMMG-HD7 trial indicated that adding Sarclisa to standard-of-care induction therapy resulted in deeper responses and higher rates of minimal residual disease negativity in newly diagnosed multiple myeloma (search) patients.
Monoclonal antibodies continue to show promise in treating multiple myeloma (search) (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.