Welcome to the first day of our recap of the latest findings on myeloma treatments reported at the International Myeloma Society (IMS) meeting that kicked off Wednesday in Rio De Janeiro, Brazil. Today gave us important updates on the several treatment combinations for first-line and maintenance therapy for patients with newly diagnosed multiple myeloma (NDMM).
The Phase 3 PERSEUS study that showed that adding Darzalex (daratumumab) to Velcade (bortezomib), Revlimid (lenalidomide), and dexamethasone (D-VRd), which has become a standard of care in the US, followed by a maintenance regimen of Darzalex (by injection) plus Revlimid (D-R) led to impressive results with more than 90% of patients with standard risk disease having no disease progression after more than 4.5 years. Patients with high-risk disease also had incredibly promising results, further indicating that this is a standard for all patients. Results from the primary analysis of the PERSEUS study were published earlier this year in The New England Journal of Medicine (Sonneveld P, 2024).
With regards to the high-risk patient population, this abstract (Abstract OA-48), researchers from Greece reported updated efficacy findings in 709 NDMM patients with chromosomal abnormalities who received either D-VRd or VRd. Chromosomal abnormalities are widely accepted markers for high risk of poor prognosis in patients with multiple myeloma, such as the presence of deletion of chromosome 17p [del(17p)], translocation of chromosomes 4 and 14 [t(4;14)], translocation of chromosomes 14 and 16 [t(14;16)], and either gain or amplification of chromosome 1q21. To learn more about high-risk myeloma and chromosomal abnormality terminology please see our FAQ blog here and our biomarkers infographic here.
Their analysis confirms the strength of this combination as a standard of care for patients with NDMM, regardless of cytogenetic status.
On September 20 the Food and Drug Administration expanded the label of Sarclisa (isatuximab-irfc) to include treatment with VRd for NDMM patients. The FDA approval was based on the IMROZ trial of 446 patients; updated results were presented at the IMS Meeting.
In this abstract (Abstract OA-53), researchers from Germany presented findings from a long-term study with 153 high-risk patients (regardless of ASCT status) who received Sarclisa, Kyprolis, Revlimid, and dexamethasone (Isa-KRd) up to 6 years ago. Patients with high-risk multiple myeloma were defined by ISS stage 2 or 3 and any of del17p, t(4;14), t(14;16), or 3 or more copies of 1q21 (amp1q21). Patients with these high-risk characteristics may have a shorter survival rate than other patients when treated with older regimens. These results were encouraging for high-risk patients with survival rates exceeding 70% at four years and 60% at six years, which is in line with survival rates for all patients.
Long-term follow-up results from this trial suggest that Isa-KRd may be an alternative treatment regimen to Dara-VRd, particularly for patients with high-risk disease.
Researchers from Spain presented data (Abstract OA-64) from an early phase trial that showed Blenrep (belantamab mafodotin) in combination with VRd (Bela-VRd) was safe and effective as first-line treatment for patients with NDMM who were eligible for an ASCT. In this study, 50 patients received Bela-VRd as first-line therapy, followed by ASCT, and then maintenance therapy with Revlimid until disease progression or toxicity and Blenrep for two years.
Eye toxicity such as blurred vision and dry eye were the most common side effects with Bela-VRd treatment. Patients who experienced these side effects were given a lower dose of Blenrep and the side effects tended to resolve quickly, while patients continued to respond to treatment. This early data continues to build evidence for the utility of Blenrep as a treatment option for patients once available.
Maintenance therapy with Revlimid (lenalidomide) is the standard of care following induction therapy and ASCT; however, all patients are at risk of relapse following transplantation, and up to 30% stop Revlimid maintenance therapy due to intolerable side effects. Thus, new treatment options with improved activity and tolerability are needed for maintenance therapy.
Iberdomide is a novel, potent oral cereblon E3 ligase modulator (CELMoD™), which is like but more potent than Revlimid, with a dual function: activate the immune system and directly kill myeloma cells by inducing the destruction of proteins that drive cancer growth.
Findings from a small, early phase clinical trial of 11 patients reported (Abstract OA-50) that iberdomide maintenance therapy following ASCT showed an improvement in response over time in patients who received Revlimid plus either Velcade or Kyprolis/PI-based induction with or without Darzalex or Sarclisa and high-dose chemotherapy with stem cell transplant (ASCT) The most common serious side effects observed with iberdomide were low blood cell counts, infections, and fatigue.
Dr Tanya Wildes from the University of Nebraska and colleagues conclude that iberdomide may represent an alternative to current standard of care Revlimid maintenance therapy strategy. Iberdomide is currently being studied (versus Revlimid) as maintenance therapy following ASCT in a phase 3 trial.
Stay tuned tomorrow for additional updates on quadruplet regimens for newly diagnosed disease and real-world evidence on CAR T-cell therapy for relapsed/refractory multiple myeloma.
