Today is effectively the final day of ASH but it was still full of information, and to be honest, I’m a bit brain-fried. However, the day was broken up with the opportunity to meet with several Pharma companies:
- Takeda (Velcade, Ninlaro), who discussed their new Patient Advocacy Liaisons (Oncology Nurses) who will offer presentations to multiple myeloma patients covering a number of topics such as Myeloma 101 and Understanding Labs in 2021.
- Karyopharm (selinexor) which reviewed the efficacy of newly approved Selinexor and its unique mechanism: XPO1 Inhibitor so that myeloma cells keep their tumor suppressors that effectively result in myeloma cell death (my layman’s explanation). In trials, Sel-Vel-dex and Sel-Pom-dex have both shown benefit over those treatments without Selinexor…for instance, SVd in groups like high-risk and frail patients improved progression-free survival (PFS) at 15 months versus 6 months and 14 months versus 9 months, respectively. Or selinexor, pomalidomide and dex (SPd) versus pomalidomide and dex produced an overall response rate (ORR) of 60% vs 40%. However, there’s been a concern with side effects, particularly GI, that this oral drug showed early-on. But now these newer trials are dosing selinexor only once a week, rather than twice. And at this lower dosage, side effects appear manageable. Also, there are not unexpected side effects. Karyopharm also has some excellent patient support programs which you can learn more about at https://www.karyforward.com/.
- Janssen Darzalex (daratumumab) and Darzalex Faspro and Cartitude (CAR T), current and future important products for treating myeloma.
And now for a few highlights from today’s ASH
An NIH study was presented on treating high-risk smoldering multiple myeloma patients with Kyprolis (carfilzomib), Revlimid (lenalidomide) and dexamethasone (KRd) for 8 cycles followed by Rev maintenance with a goal to prevent symptomatic MM. Impressive results for 54 patients:
- 8 year, progression-free survival—91%
- 8 year overall survival—100%
- Overall response rate (ORR)—100% (>=Very Good Partial Response —94%),
- and minimal residual disease negative—70%.
So after 8 years, only 10% developed multiple myeloma whereas with no treatment, historical rates show that 75% would have progressed. 
- Griffin: This trial examines the benefit of four-drug induction, adding daratumumab at every stage except stem cell transplant: Velcade, Revlimid, and dex plus stem cell transplant; Velcade, Revlimid, and dex; and consolidation-Revlimid maintenance. Then, these 2 arms were compared after 12 months of maintenance. The Dara arm favored all comparisons: 10-5 MRD- 62% vs 27%; Complete Response (CR) 82% vs 61%. However, at 27 months f/u, there’s no different yet in PFS or OS. Will DaraVRd become a standard? 
- TOURMALINE-MM2: Isatuximab, Revlimid, and dex versus placebo, Revlimid, and dex for transplant ineligible newly diagnosed multiple myeloma patients (pts). N=705 pts. 18 cycles followed by reduction till progression improved PFS by 13 months (35 vs 22 mos). ORR 82% vs 80% similar but deeper responses shown by CR 26% vs 14%. The presenter indicated that this all-oral therapy was comparable to VRd but that DaraRd was probably better. 
- There were 2 very interesting biological studies: 1) The first revealed an enzyme called APOBEC. When mutated in MGUS or SMM, this led to higher progression to MM (80%) versus normal APOBEC activity showed lower progression (13%).  2) BCMA is becoming a common target of immunotherapies CAR-T and BiTEs and more. But after treatment with one of these, what about being treated again with a different BCMA-targeted drug? There was a presentation indicating that a tumor-intrinsic factor resulting in loss of BCMA expression may make subsequent BCMA-targeted treatment less effective. In addition, patients with del16p and del17p may develop tumor-intrinsic resistance. .
- The first results of Iberdomide (CC-220) + dex, with either Dara (N=27) or Vel (N=23) for relapsed/refractory multiple myeloma (RRMM) were presented, although numbers are small. Importantly Iber (which binds to Cereblon) was shown to be effective in patients who were resistant to Rev and Pom. The ORR for the Dara and Vel arms were 42% and 61% respectively even though most patients were refractory to Dara and Vel. 
Finally, there was also a very important Education session where myeloma expert doctors presented information and the answered question about treating difficult Myeloma cases that involved: Renal (kidney) insufficiency (RF), Plasma Cell Leukemia (PCL), Extramedullary Disease (EMD), and Central Nervous System (CNS) disease. Some of my takeaways were:
- RF: Dose-reduce Rev but not necessary for Pom. PI’s and mAb’s also ok with no dose reductions and SCT can be effective.
- EMD: Vel, DCEP treatments
- CNS: Unusual (1-2%) but radiation, dex, IMIDs, Selinexor cross the bloo-brain barrier and can be effective.
Well, that’s it for 2020 ASH, although I’ll likely created a blog with my final thoughts. This “virtual” platform worked out well, though I did miss connecting face-to-face with others.
Be your own best patient advocate.
— Jack Aiello, on Twitter @JackMAiello