Day 2 ASH: Some new drugs, new processes

Today’s oral presentations examined prognostic factors for newly diagnosed multiple myeloma patients, new drugs, 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 longtime friends of mine. It was so nice to see them called out for their unrelenting advocacy work.

Now to those abstracts:

1. Circulating clonal plasma cells (CCPC) are potentially cells found in our blood stream at diagnosis. Quantifying these using multi-color flow cytometry provides an independent biomarker for the prediction of progression free survival (PFS) and overall survival (OS), perhaps being more informative than the International Staging System (ISS), the Revised International Staging System (R-ISS), and other multiple myeloma staging guidelines. [P Tembhare, See ASH Abstract 469.]
2. These abstracts both focused on Quality of Life (QoL) issues as determined by Patient-Reported Outcomes (PROs):
   • For frail patients, QoL benefits were seen in the MAIA study comparing Daratumumab, Revlimid and dexamethasone (DRd) with Revlimid and dexamethasone (Rd). The Dara arm showed benefit in pain symptoms and global health over Rd alone while both arms improved fatigue, emotional and social functions. [A Perrot. See ASH Abstract 472.]
     
   • For transplant-eligible patients, the GRIFFIN trial (Dara +/- [Velcade, Revilimid and dexamethasone, or VRd->stem cell transplant->VRd->R]) PRO analysis concluded that the Dara arm resulted in greater improvements in health-related QoL, with a notable reduction in pain. [R Silbermann, See ASH Abstract 473.]
3. Modakafusp alfa (“Moda”) fuses interferon (the killing machine) to a CD38 monoclonal antibody (multiple myeloma cell locator) from Takeda in relapsed/refractory multiple myeloma patients (RRMM), N=30 at 1.5mg/kg dose every 4 weeks, and showed a 43% ORR (39% for prior refractory CD38, 27% prior BCMA but 60% no prior BCMA). It had no constitutional or neurological side effects seen with the “original” interferon, but it did have cytopenias. Note that adding dex to Moda didn’t seem to make a difference. [D Vogl, See ASH Abstract 565.]
4. BMS-986354 CAR-T (BCMA) uses the NEX-T manufacturing process for N=65 RRMM with metastatic, or mLOT=5, and overall response rate (ORR)=95.1% as well as cytokine release syndrome (CRS) 80% all G1/2 except 1xG3 pt. The unique part of this presentation was the manufacturing process of only 1 week, compared with 4-5 weeks for today’s CAR-Ts. [L Costa, See ASH Abstract 566]
5. Since CRS is a major issue with most CAR-T’s and bispecifics, this study provided the bispecific cevostamab (FcRH5 x CD3) with either pretreatment of tocilizumab (“toci” often used to treat CRS) or no pretreatment. The pretreatment arm resulted in lower CRS (39% v 91%) as well as better ORR (55% v 37%). [S Trudel, See ASH Abstract 567.] Another cevostamab study showed that after 1 year of fixed length treatment, some patients maintained their response a year later, but data is small and early. [A Lesokhin, See ASH Poster 1924]
6. Mezigdomide (“Mezi”) is one of the cereblon E3 ligase modulator (CelMods) from BMS/Celgene, more powerful oral therapies than their earlier immunomodulatory drugs (IMiDs) Rev and Pomalidomide (Pom). For N=101 RRMM patients with >= 3 LOT, Mezi (1 mg/day 1-21) plus dex was given. ORR=41% (30% for patients with plasmacytomas, 50% for patients with prior BCMA). Going forward, Mezi will be combined with Kyprolis (carfilzomib) and dexamethasone, Velcade and dexamethasone (Vd), and Dara. [P Richardson, See ASH Abstract 568.]
7. The other CelMod is called iberdomide, which is less potent, so may be used earlier while Mezi gets used later. A study with iber (1.6 mg/day 1-21) + dex for RRMM N=41 with prior anti-BCMA therapy showed ORR 34.1%, mDoR 7.5 mos, and mPFS 2.3 mos. [S. Lonial, See ASH Poster 1918.]
8. ABBV-383 monotherapy at 40mg (N=55) and 60mg (N=61) Every three weeks (Q3W) doses are well tolerated in patients with RRMM. Durable responses (ORR 58%, 61% response) were observed at both doses, including in patients with triple-refractory RRMM. mPFS was long (13.7, 11.2 months). CRS 70% all but 1 patient was G1/2. G3 infections were 22%. [P Voorhees, See ASH Poster 1919.]
9. A “dex-sparing” regimen of Dara-Rev (DR) in frail, newly diagnosed multiple myeloma patients was compared with Rev-dex (Rd). DR showed better ORR (96% v 85%), but PFS analysis is ongoing. Personally, I was disappointed this study didn’t use patient Patient-Reported Outcomess. And DRd might have been a more informative arm. [S Manier, See ASH Abstract 569.]
10. How long should patients take maintenance treatment after a transplant? This study looked at patients in the large Myeloma XI trial. It concluded that there’s less value in the 5th year of maintenance than years 1-4, so perhaps there’s a stopping time between years 4 and 5? If the patient had sustained minimal residual disease negativity (MRD-), the data showed that they should still get maintenance for 3 years. Newer trials randomizing patients after sustained MRD-negativity (MRD-) are needed. [C Pawlyn, See ASH Abstract 570.]
11. Circulating Plasma Cells (CPC) was shown to perhaps be a better prognostic factor than bone marrow biopsy/aspirate for newly diagnosed multiple myeloma patients. [E Terpos, See ASH Abstract 647.]

That’s it for today. Tomorrow is the final whole day of ASH, but then I’ll personally be spending time of trying to digest all of this amazing information.

Be your own best patient advocate.

— Jack Aiello, on Twitter @JackMAiello