Review of Primary Outcomes from the PERSEUS Trial of Subcutaneous DARA+VRd in Transplant-Eligible Newly Diagnosed Multiple Myeloma

EP: 1.Patient Profile: A 54-Year-Old Woman with Newly Diagnosed Multiple Myeloma

EP: 2.Overview of Results from the DETERMINATION Trial of RVd plus ASCT for Newly Diagnosed Multiple Myeloma

EP: 3.Discussion of Final Analysis of the GRIFFIN Study Comparing DARA+RVd versus RVd

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EP: 4.Review of Primary Outcomes from the PERSEUS Trial of Subcutaneous DARA+VRd in Transplant-Eligible Newly Diagnosed Multiple Myeloma

EP: 5.Overview of the IsKia Trial Results Evaluating Isatuximab + KRd in Transplant-Eligible Newly Diagnosed Multiple Myeloma

EP: 6.Summary of Final Analysis from the MASTER Trial of DARA+KRd

EP: 7.Discussion of Phase 2 IFM 2018-04 Study Data Presented at 2023 ASH Examining DARA+VTd with Tandem ASCT for High Risk Transplant-Eligible Newly Diagnosed Multiple Myeloma

EP: 8.Key Clinical Insights for the Management of Newly Diagnosed Multiple Myeloma

Case: A 54-Year-Old Woman with Newly Diagnosed Multiple Myeloma (NDMM)

Clinical Presentation:

• FH is a 54-year-old woman who presents to her physician with complaints of back pain, fatigue, nausea, constipation, and occasional, but recurring dizziness

Initial Clinical Workup and Diagnosis:

• Hb 7.0 g/dL
• Calcium 11.3 mg/dL
• Creatinine, 1.5 mg/dL
• Albumin, 3.2 g/dL
• β2-microglobulin, 6.0 mg/dL
• LDH 200 U/L
• Bone marrow biopsy showed monoclonal plasma cells, 22%.
• Serum monoclonal protein, 5.0 g/dL
• Serum kappa FLC, 240.0 mg/L
• FISH: (+) IGH Translocations; none
• ECOG PS 1
• AG was diagnosed with R-ISS stage II/R2-ISS stage III IgG-kappa myeloma.
  • CAR T eligible

Treatment:

• Patient was initiated on daratumumab/bortezomib/ lenalidomide/ dexamethasone (D-VRd) induction therapy prior to receiving ASCT, followed by lenalidomide maintenance therapy.
  • She achieved VGPR post-induction, and
  • Maintained VGPR post-ASCT

This is a video synopsis/summary of a Case-Based Peer Perspectives featuring Douglas Sborov, MD.

The phase 3 PERSEUStrial compared subcutaneous daratumumab plus lenalidomide, bortezomib, and dexamethasone (Dara-RVD) with RVD alone in patients with transplant-eligible newly diagnosed multiple myeloma. Data were first presented at the 2023 American Society of Hematology Annual Meeting and Exposition. The design mirrored the Griffin trial, except for maintenance therapy. The Dara-RVD arm had 2 years of Dara-lenalidomide maintenance, with those patients with minimal residual disease (MRD) positive continuing Dara-lenalidomide and those who were MRD negative continuing lenalidomide alone. Primary end point was progression-free survival (PFS); key secondary end points included response rates, MRD negativity, safety, and overall survival.

PERSEUS solidified quadruplet over triplet therapy in this population based on the significantly improved PFS. As in Griffin, Dara-RVD improved response rates, complete response, and MRD negativity vs RVD consistently across subgroups. Complete response or better rate was 87.9% with Dara-RVD; MRD-negativity rate (10-5 threshold) was 75.2%. At 47.5-month median follow-up, PFS was significantly improved with Dara-RVD (4-year PFS, 84.3%). Whereas Griffin was underpowered for PFS, PERSEUS resolved prior doubts, cementing quadruplet therapy as standard of care for patients with transplant-eligible newly diagnosed multiple myeloma. However, there is debate over the optimal proteasome inhibitor and anti-CD38 antibody in quad regimens.

Video synopsis is AI-generated and reviewed by Targeted Oncology® editorial staff.