Patients eligible for transplant

Phase II GRIFFIN study topline results released

The phase II GRIFFIN study (MMY2004, NCT02874742) investigated the use of daratumumab (dara) in combination with bortezomib (V), lenalidomide (R), and dexamethasone (d; dara-VRd) in patients with newly diagnosed multiple myeloma (NDMM) who are eligible for high-dose chemotherapy and autologous stem cell transplant (ASCT). This was compared to VRd alone1

During the American Society of Hematology (ASH) meeting in San Diego, US, 2018, study investigators reported the quadruplet regimen (dara-VRd) had a manageable toxicity profile, and achieved minimal residual disease (MRD) negativity (10-5) in 50% of patients post-consolidation.2

It has now been announced that the study has met its primary endpoint with a higher percentage of patients achieving a stringent complete response (sCR) with dara-VRd compared to VRd alone.1

Given as dara-VRd versus VRd unless otherwise stated

  • Study design: This randomized, open-label study compared dara-VRd to VRd in 223 patients. The primary endpoint was sCR post-consolidation1
  • Efficacy:1
    • sCR: 42.4% vs 32.0%
      • Odds ratio: 1.57
        • 95% CI, 0.87-2.82
        • p = 0.1359
    • This exceeded the statistical significance at the pre-set 2-sided alpha level of 0.2
  • Safety: The safety profile of the dara-VRd quadruplet was similar to that reported for the drugs when used separately.1
  • Future directions: The company responsible for the study has initiated two phase III studies – PERSEUS and CEPHEUS in frontline multiple myeloma (MM) indications.1
Conclusion

These results add to the evidence that the addition of daratumumab to traditional triplet induction regimens can improve efficacy. This was supported by the CASSIOPEIA, part one, trial results which showed that daratumumab in combination with V + thalidomide (T) + d (dara-VTd), improved efficacy in the transplant eligible, NDMM setting. In the CASSIOPEIA trial, dara-VTd gave a 53% reduction in the risk of progression or death compared to VTd alone.3

The development of an optimal induction regimen for ASCT has evolved significantly in recent years, and was discussed by Professor Mohamad Mohty during the 45th Meeting of the European Society for Blood and Marrow Transplantation (EBMT), 2019. During this presentation, Professor Mohty noted that the GRIFFIN trial, using daratumumab in combination with a traditional triplet, like VRd, creating a quadruplet (dara-VRd), was one of the most recent innovations in ASCT induction regimen optimization.4

Additionally, the recent results of the COLUMBA trial, showing subcutaneous administration of daratumumab is non-inferior to intravenous administration, may further increase uptake of daratumumab-containing regimens, whilst increasing the patient’s quality of life during treatment.5

References
  1. Genmab Announces Positive Topline Results in the Phase II GRIFFIN Study of Transplant Eligible, Newly Diagnosed Patients with Multiple Myeloma Treated with Daratumumab in Combination with Lenalidomide, Bortezomib, and Dexamethasone. https://ir.genmab.com/news-releases/news-release-details/genmab-announces-positive-topline-results-phase-ii-griffin-study [accessed 2019 Jul 09]
  2. Voorhees P. M. et al. Efficacy and Updated Safety Analysis of a Safety Run-in Cohort from Griffin, a Phase 2 Randomized Study of Daratumumab (Dara), Bortezomib (V), Lenalidomide (R), and Dexamethasone (D; Dara‐Vrd) Vs. Vrd in Patients (Pts) with Newly Diagnosed (ND) Multiple Myeloma (MM) Eligible for High‐Dose Therapy (HDT) and Autologous Stem Cell Transplantation (ASCT). 2018 Nov 21. Abstract #151. ASH 60th Annual Meeting and Exposition, San Diego, US
  3. Moreau P. et al. Phase 3 randomized study of daratumumab + bortezomib/thalidomide/dexamethasone (D-VTd) vs VTd in transplant-eligible newly diagnosed multiple myeloma: CASSIOPEIA Part 1 results. 2019 Jun 02. Abstract #8003. American Society of Clinical Oncology meeting 2019, Chicago, US.
  4. Mohty M. et al. Multiple myeloma (MM) treatment in real-world clinical practice: a focus on induction regimens prior to autologous stem cell transplantation (auto-SCT) from the prospective, multinational, non-interventional EMMOS study. 2019 March 27. Abstract #OS12-3. 45th Annual Meeting of the European Society of Blood and Marrow Transplantation (EBMT), Frankfurt, DE
  5. Mateos M-V. et al. Efficacy and safety of the randomized, open-label, non-inferiority, phase 3 study of subcutaneous (SC) versus intravenous (IV) daratumumab (DARA) administration in patients (pts) with relapsed or refractory multiple myeloma (RRMM): COLUMBA. 2019 Jun 02. Abstract #8005. American Society of Clinical Oncology meeting, Chicago, US.
Download this article:

You can now download this article in Adobe PDF® format.

Download as PDF
Was this article informative? Thank you for your feedback!