Overview of the IsKia Trial Results Evaluating Isatuximab + KRd in Transplant-Eligible 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 Perspective featuring: Douglas Sborov, MD.

The phase 3 IsKia trial compared carfilzomib, lenalidomide, and dexamethasone (KRD) with isatuximab-KRD (Isa-KRD) in patients with transplant-eligible newly diagnosed multiple myeloma. Patients received Isa-KRD or KRD induction, autologous stem cell transplant, then consolidation with their induction regimen, then dose-reduced 3- or 4-drug consolidation for 12 cycles. The primary end point analysis presented was minimal residual disease (MRD) after the first 4 consolidation cycles.

As in most frontline trials, less than 20% of patients had high-risk cytogenetics. MRD-negativity rates (10-5 and 10-6 thresholds) were significantly higher with the Isa-KRD quadruplet vs KRD triplet: 77% and 67% for Isa-KRD vs KRD, respectively. As seen previously, MRD negativity improved over time and was high across cytogenetic-risk subgroups for quadruplet therapy.

Data continue to show superior responses and progression-free survival with quadruplets over triplets up front. The choice between daratumumab vs isatuximab or bortezomib vs carfilzomib should depend on patient factors.

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