Inaugural post: MM Fighters Breakdown of ASH 2023 - Part 1
Our first post for the myeloma fighters! Breakdown of ASH 2023 for Multiple Myeloma. Please note: These opinions are my own and do not represent the positions of UW Medicine.
Welcome, myeloma fighters! I am Andrew Cowan, MD, an Associate Professor of Medicine at UW Medicine and Fred Hutch, and the clinical director of the multiple myeloma service at Fred Hutch and UW Medicine. After many discussions with the well-established multiple myeloma fighters patient group in Seattle, WA, we have created a Substack to help reach the broader community with patient-friendly information about updates in multiple myeloma treatment and supportive care. This Substack is meant to be interactive and fun. I will try to respond to messages and notes as I can, but will be posting here on a quarterly basis.
For our first post, I thought it would be useful to provide a breakdown of the ASH 2023 meeting in San Diego, California, with a focus on what’s exciting in multiple myeloma! For those not familiar, every year, the American Society of Hematology hosts a large congress in early December, where the most exciting new research and clinical trials are presented. I am going to focus this post on the most exciting clinical trial data for newly diagnosed multiple myeloma. In a future post, I will focus more on the basic and translational research, and studies in relapsed MM, that were most exciting and impactful from this meeting.
Newly Diagnosed Multiple Myeloma - Updates from ASH 2023
There were so many exciting trials presented for newly diagnosed MM in 2023 at ASH - it’s hard to pick where to start!
However, I think the trial that attracted most attention (and rightfully so) were the results of the phase 3 PERSEUS trial - a randomized trial comparing the combination of Dara RVd induction to RVd in a transplant eligible population of newly diagnosed multiple myeloma patients. A link to the abstract is here.
The PERSEUS trial (details shown below) design is similar to the randomized phase 3 GRIFFIN trial, the results of which have been previously published in Blood and Lancet Haematology.
PERSEUS Trial Design (Ref: https://www.myeloma-europe.org/trials/emn-17/).
The key different between PERSEUS and GRIFFIN, as astute readers may note, is the inclusion of daratumumab discontinuation after 1 year of sustained MRD negativity. This trial demonstrated that use of Dara RVd induction and consolidation resulted in improved PFS, 84.3% at 2 years for the Dara RVd group, and 67.7% at 2 years for the VRd group. PFS means “progression free survival”.
PFS stands for Progression-Free Survival, which is a term we use in medicine to describe the length of time during and after treatment that a patient lives with a disease, such as cancer, without it getting worse or the patient passing away from any cause. Essentially, it’s a way to measure how effective a treatment is in keeping the disease under control.
This trial confirms the significant benefits seen with Dara RVd for newly diagnosed multiple myeloma in the randomized phase 2 GRIFFIN trial. In this myeloma doctor’s opinion, these findings cement Dara RVD as a standard for patients with newly diagnosed multiple myeloma who are transplant eligible.
The second clinical trial that garnered deserved attention were the results of the randomized phase 3 IsKIA trial, a randomized trial comparing Isatuximab, carfilzomib, lenalidomide, and dexamethasone, to carfilzomib, lenalidomide, and dexamethasone for patients with newly diagnosed transplant eligible multiple myeloma. Readers might note that KRd (carfilzomib lenalidomide and dexamethasone) is not widely used - which is largely due to the results of the phase 3 ENDURANCE trial that failed to show a PFS benefit for KRd as compared to RVd. That said, interest in carfilzomib in newly diagnosed multiple myeloma has persisted, and further efforts are underway to re-look at carfilzomib vs bortezomib in newly diagnosed MM in randomized trial.
The trial study design was similiar to PERSEUS, except that in both arms, consolidation and light consolidation with either Isa KRd or KRd were continued for 4 and 12 cycles, respectively, post autologous stem cell transplantation. As expected, the Isa KRd regimen outperformed KRd, specifically with respect to achievement of MRD negativity at 10 to the minus 6, which as many readers may know, is the sensitivity achieved with next generation sequencing of the IGH (the most common assay for this is Adaptive Clonoseq’s MRD assay in the US).
Strikingly, post-consolidation, 67% of patients receiving Isa KRd achieved MRD negativity at 10 to the minus 6, as compared to 48% who received KRd. The PFS and OS data were not mature enough to present at the meeting, but even just the MRD results were remarkable. The Isa KRd combination was also proven to be safe, with <5% of patients in either arm experiencing grade 3/4 cardiac disorders, and comparable proportions of patients with infections (36% all grade in Isa KRD vs 32% all grade with KRd).
In summary - for newly diagnosed multiple myeloma, transplant eligible, this ASH 2023 has revealed the superiority of the CD38, proteasome inhibitor (PI), immunomodulatory (IMID) agent and steroid combinations over the PI/IMID/steroid combination alone. I would argue that these data strongly support the routine use of this regimen in this patient population based on the PFS and MRD data that were presented.
That’s all for today. Please send feedback! Look forward to engaging with the myeloma patient community.