GRIFFIN Trial: D-RVd in Transplant-Preferred Newly Diagnosed MM

Natalie Callander, MD, reviews the results and quality-of-life outcomes from the GRIFFIN trial on Dara-RVd for patients with transplant-eligible NDMM.

Case: A 61-Year-Old Woman with Transplant-Preferred Newly Diagnosed Multiple Myeloma (NDMM)

  • Patient ML is a 61 y/o woman.
    • PMH: Hypertension (well controlled on medication)
    • SMH: Does not smoke; drinks occasional glass of wine in social setting; Walks with friends 2-3 times weekly.

Clinical Presentation:

  • In October 2022, ML visited her PCP for her annual checkup. She reported having persistent pain in her shoulders.

Clinical Workup and Diagnosis:

  • Calcium 13.2 mg/dL
  • LDH 600 U/L (> ULN)
  • CrCl, 45 mL/min
  • Hgb, 7.0 g/dL
  • Beta-2-microglobulin, 6 mg/dL
  • Bone marrow biopsy showed 24% monoclonal plasma cells.
  • Serum monoclonal protein, 5 g/dL
  • Serum kappa FLC, 200 mg/dL
  • Del(17p) cytogenetic abnormalities were detected by FISH.
  • PET-CT showed osteolytic lesions in the shoulders; no EMD.
  • ECOG PS 1
  • ML was diagnosed with ISS stage II/R-ISS stage III IgG-kappa myeloma; determined to be transplant-preferred.

Current Treatment:

  • After discussions with her family and clinical team, ML was initiated on Daratumumab/bortezomib/lenalidomide/dexamethasone induction therapy (D-RVd).
  • Post-induction therapy, ML achieve very good partial response (VGPR).
  • Patient underwent stem cell mobilization and 3 months later underwent ASCT.
    • Post-ASCT response: VGPR


Natalie Callander, MD: The GRIFFIN trial [NCT02874742] is a randomized multi-center phase 2 trial that looked at using the standard regimen, which was RVd [lenalidomide, bortezomib, and dexamethasone; VRd] plus transplant, plus some consolidation. And then RVd maintenance vs the combination with the inclusion of daratumumab, both as part of the induction for 4 cycles. Transplant occurs, then consolidation followed by daratumumab with lenalidomide maintenance. And the GRIFFIN study has been presented now a few times, and we certainly have seen a PFS [progression-free survival] advantage. But what’s been updated recently is that there’s really an MRD [minimal residual disease] advantage as well for the combination using daratumumab. And in particular, that is very true for patients who are judged to have either 0 or 1 high-risk cytogenetic feature. They seem to do quite well with this treatment combination. And there’s a little bit less durability of MRD negativity, which is quite high in this study for those who have 2 or more high-risk cytogenetic abnormalities, but they still benefited over VRd.

One of the reassuring things is that there has been a concern that the inclusion of daratumumab would increase the rate of adverse effects, very significant adverse effects, and impact negatively on the quality of life. And 2 of the things that we got to see at ASH [American Society of Hematology Annual Meeting] were some long-term data looking at adverse events. And really there is not a big difference. There is somewhat more neutropenia in the quadruplet regimen, but it ended up being not that significantly different for other adverse effects. And Connie Silverman, DNP, FNP, from Oregon Health & Science University in Portland, Oregon, presented some very nice data, specifically looking at the quality of life in people who were treated on the GRIFFIN trial. The idea was when using a quadruplet regimen, you’re really going to negatively impact the quality of life. And she was able to show in her analysis that, No. 1, they had a high rate of return on these QOL [quality of life] questionnaires. Sometimes that happens in studies, that very few people fill them out, but the majority of patients did. They were able to show that there seemed to be an improvement in the quality of life for the quadruplet vs the triplet, although both groups improved.

But one of the very interesting take-home messages for me was that when you looked at going through the package of treatment, so that is moving on through maintenance, if you look at the first time that there was a decline in global health scores, it was significantly longer for the quadruplet for daratumumab plus VRd. [It was] somewhere close to 4 years vs only about 16 or 17 months for people on VRd before they started to show a deterioration in their quality health. I think it was a very important presentation.

Transcript edited for clarity.

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