Urvi Shah Profile picture
22 Nov, 25 tweets, 28 min read
With #ASH20 around the corner, I wanted to share a summary of the major myeloma immunotherapy - CARs, Bispecifics, ADCs trials and #ASH20 abstracts to look out for #mmsm from a recent talk I gave bmj.com/content/370/bm…
I will focus on some of the major drugs in this thread (in the blue boxes). Although I may not be able to cover all of them, the trials I have typed over the image are the ones to watch out for at #ASH20
We will see updates at #ASH20 for cilta-cel (JNJ-4528) and P-BCMA 101. We will see subgroup analyses and correlative data for KarMMa and EVOLVE studies.
Here is a summary of all the ongoing KarMMa Trials (bb2121)
CRB-401 (bb2121)- Initial data for 33 patients was published in @NEJM @NoopurRajeMD
Updated data for 62 patients will be presented by Lin et al. at #ASH20 - ORR 76%, mPFS 8.8 months, CRS 76% and NT 44%
CRB-402 (bb21217)- ORR 55%, mDOR 11.9m at 15-450 million cells, CRS 67%, NT 22% will be presented by Alsina et al. #ASH20

KarMMa (ide-cel, bb2121) - Data was presented at #ASCO20 however we will see updates on subgroup analyses presented by @NoopurRajeMD for high risk MM, @ninashah33 for QOL improvement, @BerdejaJesus for elderly and @kansagraMD for CRS characterization #ASH20 #mmsm
EVOLVE (orva-cel, JCARH125) - Data presented at #ASCO20 by Sham Mailankody ORR 92%, PFS not reached. Orva-cel is characterized by a predominant central memory phenotype with high in vitro and in vivo proliferative potential - Colonna et al. #ASH20
Here is a summary of the three ongoing CARTITUDE trials
CARTITUDE-1 (cilta-cel, JNJ-4528) was presented @DMadduri at #ASH19 and @BerdejaJesus #ASCO20 ORR 100% in 29 patients. @DMadduri will present data for 97 patients - ORR 95%, mPFS not reached, CRS 95%, NT 21%
P-BCMA 101 - piggyBac system creates a product with high percentage of Tscm cells presented #ASH18 @TaraGregoryMD Updates at #ASH20 for 43 patients ORR 57%, CRS 17% by @Ccostello7
Allo-715 (allogeneic or off the shelf CAR T cell therapy) updates at #ASH20 by Sham Mailankody et al. @sloan_kettering for 19 patients.
This slide is a summary of the BCMA targeted bispecific data that was available prior to #ASH20. At #ASH20 we will see the data for many other bispecifics (see thread below) #mmsm @MM_Hub @myelomacrowd
AMG-701 - Updates @ASH_hematology by Harrison et al. @SLentzsch Phase 1 study, 75 patients, ORR 36% at 3-12mg dose, CRS 60% #ASH2020
Teclistamab - Initial promising data presented @ASCO #ASCO20 by @szusmani We will see updates at #ASH20 by @AlGarfall for 128 patients (SC or IV) - ORR at active doses 64%, mDOR NR, CRS 53%
PF-3135 BCMA bispecific - SC weekly, 18 patients, ORR 33%, ORR at highest 2 doses 75%, CRS 61% to be presented at #ASH20 by @LesokhinMD #mmsm
CC-93269 BCMA 2+1 bispecific was presented @ASCO #ASCO20 by @End_myeloma ORR 43% but 89% at highest doses, CRS 77% in 30 patients.
REGN5458 BCMA bispecific, 45 patients, ORR 36% (60% at highest dose level), CRS 38% to be presented at #ASH20 by @DMadduri
Talquetamab - first GPRC5D bispecific, phase 1, 137 patients, IV ORR 78%, SC ORR 67%, CRS 47%, NT 5%. Another very promising target. #ASH20 by Chari et al. The first GPRC5D CAR trial is recruiting @MSKHemOncTrials NCT04555551 ash.confex.com/ash/2020/webpr…
BCFR4350A - FcRH5 bispecific. Phase 1 study ORR 52% at all dose levels. More data to be presented at #ASH20 @CohenAd_MMdoc
The first BCMA Antibody Drug Conjugate - Belantamab mafodotin was recently approved for MM in 2020. Here is the data behind this approval and the updates that will be presented at #ASH20
DREAMM-1 phase 1 study Trudel et al published rdcu.be/ca9Gi
DREAMM-2 phase 2 study was published by @SagarLonialMD et al. in Lancet Oncol 2019. We will see 1 year outcomes at #ASH20 ORR 30-34%, mPFS 2.2-2.9m.
DREAMM-6 - Belamaf, Vd was presented at #ASCO20 by @AjayNookaMD with an ORR 78%. We will see updates at #ASH20 presented by @DrRakeshPopat Expected AEs corneal events common but manageable
Belamaf Pom Dex - phase 1 part 1, 35 patients, ORR 86%, Trudel et al. to be presented at #ASH20 Promising efficacy for a new combination.
MEDI2228 Another BCMA ADC with less corneal toxicity - 82 patients, MTD 0.14 mg/kg q3w, ORR 61%, mDOR NR, photophobia 54% but no visual loss, 24 discontinued treatment in the 0.14 mg/kg cohort, to be presented #ASH20 by @myelomaMD

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