Jakubowiak Talks Daratumumab Quadruplet Therapy and the GRIFFIN Study at 2021 ASH

In an interview at the 2021 ASH Annual Meeting, Andrzej Jakubowiak, MD, PhD, talks about daratumumab-based quadruplet therapies being evaluated in clinical trials and the potential impact they’ll have on the multiple myeloma treatment landscape.

At the 63rd American Society of Hematology Annual Meeting & Exposition, Andrzej Jakubowiak, MD, PhD, director of the Myeloma Program at University of Chicago Medicine, spoke about which research he was most excited to see the results of. In an interview with CancerNetwork®, he detailed results of the GRIFFIN trial (NCT02874742) of daratumumab (Darzalex) added to lenalidomide (Revlimid), bortezomib (Velcade), and dexamethasone (D-RVd) in conjunction with autologous stem cell transplant (ASCT), followed by daratumumab plus lenalidomide maintenance vs RVd and lenalidomide maintenance alone for patients with newly diagnosed multiple myeloma.1


The one [presentation] which probably made biggest impact—not only on me, but many of us—is updated results from the GRIFFIN trial. This is a trial in which newly diagnosed patients are treated with [D-RVd or] RVd, which has been our most common choice of initial treatment in the United States until recently, or standard of care. In this trial that was updated at this meeting, the addition of the antibody daratumumab to RVd in the treatment plan, which includes transplant after 4 cycles and additional maintenance with daratumumab and lenalidomide, generates very good results. This phase 3 randomized trial generated clearly superior depth of response, complete responses, and MRD [minimal residual disease] negativity, but now we are seeing very clear separation of Kaplan-Meier curves of superior progression-free survival on daratumumab compared with the RVd arm without daratumumab, which is [producing a] hazard ratio under 0.5. For most larger studies, this is statistically significant; [however, this trial] has not yet reached such statistical significance at this point. It is anticipated that this will be provided at the next meeting and further evaluated in another larger similar study, the PERSEUS trial [NCT03710603], which in a larger patient group, patients will be able to establish this treatment strategy as one of the top choices and possibly standard of care across the United States and the world.

I would add that in a similar way, but it was not a randomized trial, there was a very impressive update from the MASTER trial [NCT03224507],2 which used a different backbone of KRd [carfilzomib (Kyprolis), lenalidomide, and dexamethasone] with daratumumab as well. Similarly, like in GRIFFIN, it was followed by transplant, followed by KRd for the duration of treatment, which was per study design, [with the achievement of] MRD negativity leading to discontinuation treatment. In this study—which is 1 arm, so it’s difficult to see how it will impact our practice—the results were probably the best we’ve seen in myeloma, with up to 80% of [patients achieving] MRD negativity and a very promising [median] PFS at this point. Quadruplets are impressing me with RVd and KRd with daratumumab most advanced with others coming. When we incorporate them into extended treatment and transplant, we achieve responses and duration of responses that we’ve never seen before.


  1. Laubach JP, Kaufman JL, Sborov DW, et al. Daratumumab (DARA) plus lenalidomide, bortezomib, and dexamethasone (RVd) in patients (pts) with transplant-eligible newly diagnosed multiple myeloma (ndmm): updated analysis of GRIFFIN after 24 months of maintenance. Blood. 2021;138(suppl 1):79. doi:10.1182/blood-2021-149024
  2. Costa LJ, Chhabra S, Callander NS, et al. Daratumumab, carfilzomib, lenalidomide and dexamethasone (Dara-KRd), autologous transplantation and MRD response-adapted consolidation and treatment cessation. final primary endpoint analysis of the MASTER trial. Blood. 2021;138(suppl 1):481. doi:10.1182/blood-2021-145494