Day 1 ASH: It’s All About Immunotherapy

Jack Aiello |

Dec 5, 2020

Today I actually began watching ASH (American Society of Hematology) President Dr. Stephanie Lee interview Dr. Fauci. I appreciated that one of the questions she asked was “Should cancer patients with compromised immune systems get the vaccine?” He said that he understands that cancer patients may actually be getting immunosuppressants, and the the efficacy of a vaccine is unclear. The vaccine causes an immune system to build up antibodies against a specific disease. Even so, he would definitely recommend getting the vaccine, summarizing that “working to some extent is better than not at all.”

Then it was off to attend a number of oral abstract presentations. The format of these 15-minute talks is for the primary investigator of the abstract to present a pre-recorded 10-minute talk with slides. The presenter then appears live on screen for five minutes to answer typed-in questions. This format mostly worked, except when there was a poor video connection during the Q&A session. However, I’m impressed with how ASH has brought this meeting together. Just think, if this virus happened even five years ago, this very important ASH meeting might have been cancelled.

Most of today’s talks focused on immunotherapy treatments in early phase development, where patient numbers are small and they mostly focus on safety and determining the Recommended Phase 2 Dosage (RP2D). Assume all of the patient numbers are small (e.g. 20-50), and all patients are heavily previously treated unless otherwise noted. Still, it’s exciting to see these new treatment options. Plus, there were very low Grade 3 Cytokine Release Syndrome (CRS) side effects. I’ll highlight a few of these treatments within categories CAR-T, Bi-Specifics T-cell Engagers (BiTEs) and Antibody Drug Conjugates (ADCs).

CAR-T [abstract#]

  • Universal – An Allo (off-the-shelf) CAR-T. Overall Response Rate (ORR, defined as at least Partial Remission) 60% with a short median follow-up (f/u) of 3 months. [129]
  • CRB-402 (bb21217) ORR=68% but recent manufacturing changes have improved treatment efficacy. [130]
  • Ide-cell (bb2121). For 62 patients with 18 months median f/u, ORR=76%, median PFS (Progression Free Survival) and OS (Overall Survival) of 9 and 34 months respectively. This CAR-T platform has been submitted to FDA for approval which many folks believe will occur quarter 1 of 2021. [131]
  • CARTITUDE: N=97 pts. ORR=97% (inc sCR=67%); 12-month PFS and OS were 77% and 89% respectively so this may well be the next CAR-T submitted for FDA approval. [177]
  • GC012F Fast CAR-T has dual targets BCMA and CD19. 94% ORR [178]
  • Others include CT053 [132, 133], P-BCMA-101 [134], C-CAR088 [182]

BiTES (and one ADC)

  • Teclistamab: BCMA x CD3. ORR = 73% at higher doses. [180]
  • AMG 701: BCMA x CD3. 26% ORR but 5 of 6 pts ORR in most recent evaluable group. 64 of 85 pts discontinued treatment but most due to MM progression, likely on lower starting doses. [181]
  • Talquetamab: GPRC5D (not BCMA) x CD3. Likely going with subQ formulation for which higher-dose ORR=69% [290]
  • Cevostamab: FcRH5 (not BCMA) x CD3, ORR = 53% for active dosage, included responses from prior BCMA patients. [292]
  • Others include REGN5458 [291], TNB-383B [293]
  • MEDI2228 ADC ORR=66% but 74% ORR for 17/23 pts on dose expansion phase. No keratopathy but photophobia (sensitivity to light). [179]

One other interesting abstract: Since about 8% of RRMM patients have a BRAF mutation, the GMMG-Birma trial gave BRAF and MEK inhibitors to these patients and saw an 83% (10 of 12 patients) gain an ORR (CR=25%, VGPR=50%). It’s interesting that hey used drugs encorafenib (BRAF inhibitor) and binimetinib (MEK inhibitor), both of which are also used in melanoma. Note: all-oral and dex-free. [294]; 2)

Posters [abstract #]

Finally, while I won’t go into any details, there were are number of posters that examined:

  1. New treatment combination, e.g. selinexor plus carfilzomib and dexamethasone (dex) [1366] as well as Sel plus Rev-dex [1393];
  2. Subgroup results such as Ide-cel CAR-T for elderly patients [1367] or isatuximab plus pomalidomide-dex for frail patients [1411]; and
  3. Treatment comparisons such Kyprolis, dex, and daratumumab versus Velcade, dex, and daratumumab [1562].

That’s it for tonight. While my first meeting tomorrow isn’t till 9:30am; one benefit of a virtual ASH is that many sessions are recorded and available for replay. So I’ll start earlier in order to watch a replay of some abstracts covering transplants for myeloma.

Be your own best patient advocate.

— Jack Aiello, on Twitter @JackMAiello

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