The morning started by meeting with Takeda, one of our IMF’s generous sponsors enabling several of us to attend ASH; the other 4 sponsors are BMS (Celgene), Janssen, Karyopharm, and Regeneron. We are so thankful for their support.
Next, I attended an Education session that addressed improving outcomes for relapsed/refractory multiple myeloma (RRMM) patients. Three questions were addressed:
- How do you treat a “functional high-risk patient, which is commonly defined as a patient who doesn’t necessarily show high-risk cytogenetics but rather shows suboptimal response (< Partial Remission) or relapses shortly (< 18 months) after induction? Dr. Francesca Gay suggested considering Kyprolis (carfilzomib), Revlimid (lenalidomide) and dexamethasone, or KRd; or if it wasn’t part of the induction, the addition of Darzalex (daratumumab, or D); or CAR T-cell therapies, which are expected to be available for earlier lines of treatment based on recent trial results.
- Dr. Monique Hartley-Brown tackled the question of relapse after induction including anti-CD38 treatment, such as daratumumab or Sarclisa (isatuximab). She reminded us not to forget about a transplant if it wasn’t part of the first line. Selinexor as well as BCMA-targeted therapies should also be considered (which includes Blenrep which hopefully will once again receive FDA approval).
- Finally, Dr. Adam D. Cohen considered treatment options after a patient relapses from BCMA treatment. Another BCMA treatment could be considered (although not the same as previously tried). A non-BCMA treatment might be preferred. Or, even a non-T cell-directed therapy might be tried.
Outcomes Research in Myeloma: What’s New?
This group of abstracts compared real-world results with prior clinical trial outcomes.
- After consolidating 8 trials in Canada, the conclusion was that the corresponding clinical trials showed median progression-free survival (mPFS) at 3-18 months higher and median overall survival (mOS) at greater than 19 months. As such, real-world patients are experiencing 44% worse PFS and 75% worse OS compared to randomized clinical trial patients. [Visram, 541]
- This study examined N=110 patients across multiple institutions and compared these real-world results with MajesTEC-1 study that resulted in FDA approval of Teclistamab. MajesTEC-1 reported an overall response rate (ORR)=63% and mPFS=12mos. In contrast, the real-world study, which included both triple class and penta-refractory, as well as prior BCMA (not allowed in MajesTEC-1) patients, ORR=62% (very similar) and 6 months PFS=52% (so likely worse). The use of prophylactics such as IVIG improved infection rates. [Mohan, 545]
Plenary Session
When your abstract is selected to be presented within the plenary session, it’s denoted as one of the top abstracts at ASH. Such was the case with Dr. Francesca Gay’s abstract: A phase III trial comparing Isa-KRd vs KRd as induction and post-stem cell transplant (SCT) consolidation (x4) and “light” consolidation (x12). The Primary Endpoint was minimal residual disease (MRD ), which is not yet approved as a surrogate for PFS or OS.
After consolidation, MRD- at 10-5 was 77% v 67% and at 10-6 67% v 48%. For very high-risk patients (with two or more high-risk factors), MRD- at 10-6 was 77% v 27%. Although MRD improved at every phase, ORR of 94% was essentially the same for both arms. Dr. Gay plans to provide one-year MRD sustainability in 2024. Yet this, along with another abstract presented this coming Tuesday, really strengthens the benefits of 4-drugs v 3. [Gay, 4]
Today’s oral presentations examined prognostic factors for newly diagnosed multiple myeloma patients, new drug and optimized treatment approaches, as well as prognostic markers. I’ll show some of the abstract results below from those sessions. We also met with representatives from Karyopharm — They manufacture Xpovio (Selinexor) and are one of the sponsors supporting the IMF’s sending patients to ASH. And, finally, the day ended with a wonderful tribute from CURE Magazine, which recognized several patient advocates including myeloma patient advocates Cindy Chmielewski (@MyelomaTeacher) and Tiffany Williams (@MyelomaHope) who are both patients and long-time friends of mine. It was so nice to see them called out for their unrelenting advocacy work.
So that’s it for today. Tomorrow is the final whole day of ASH but then I’ll personally be spending time off trying to digest all of this amazing information.
Be your own best patient advocate.
— Jack Aiello, on X (Twitter) @JackMAiello