Discussion of Final Analysis of the GRIFFIN Study Comparing DARA+RVd versus RVd

Opinion
Video

Discussion of the final data analysis comparing daratumumab plus lenalidomide, bortezomib and dexamethasone to lenalidomide, bortezomib and dexamethasone alone.

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 2 GRIFFIN study investigated adding daratumumab to standard-of-care lenalidomide, bortezomib, and dexamethasone (RVD) in the autologous stem cell transplant setting. Two arms were compared: RVD induction, transplant, RVD consolidation, and lenalidomide maintenance vs daratumumab-RVD (Dara-RVD) induction, transplant, Dara-RVD consolidation, and Dara-lenalidomide maintenance. Primary end point was stringent complete response rate after consolidation. Secondary end points included response rates, minimal residual disease (MRD) negativity, progression-free survival (PFS), overall survival, safety, and quality of life. Final analysis occurred after 1 year or more of maintenance.

Ultimately, GRIFFIN showed Dara-RVD improved overall response, complete response/better, and MRD negativity rates over time vs RVD. By trial end, complete response or better rate was 83% and MRD negativity rate (10-5 threshold) was 64% with Dara-RVD. The primary end point was met. At 50-month median follow-up, Dara-RVD led to a 55% reduction in disease progression/death risk. Along with other data, Griffin set the stage for adoption of quadruplet regimens in the US and for the PERSEUS phase 3 trial powered for PFS comparing quadruplet and triplet regimens.

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

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