Al-Ola A Abdallah, Associate Professor and Plasma Cell Disorder Program Director of the Division of HMCT at the University of Kansas Medical Center, shared a post on X:
“Dual-Target CAR-T Strikes Hard in EMD: ORR 97%, PFS 6 months! Is Persistence the Missing Piece?
Anti-BCMA/GPRC5D bispecific CAR-T showed impressive early activity.
Study: Single-center, open-label phase II trial.
- N=37 RRMM patients with extraosseous EMD.
- Anti-BCMA/GPRC5D bispecific CAR-T.
- Median follow-up: 10.1 months.
Historically, EMD remains one of the biggest unmet needs in myeloma.
Efficacy signals:
- ORR: 97%
- sCR: 43%
- MRD negativity: 97%
For a population with aggressive biology and prior heavily treated disease, these response rates are striking.
But durability tells another story:
- Median DOR: 5 months.
- Median PFS: 5.8 months.
- Median OS not reached.
Excellent early disease control… But maintaining remission remains challenging.
Interesting observation.
Bone marrow MRD negativity often persisted despite progression.
Progression frequently manifested as:
- New/increasing plasmacytomas.
- Extramedullary progression.
- Rising markers.
Suggests BM MRD is not equal to whole disease biology in EMD.
Safety:
CRS: 73% – All Grade 1-2.
ICANS: 5%
No treatment-related deaths reported.
Overall toxicity appears manageable and similar to currently available CAR-T platforms.
GPRC5D on-target effects:
- Nail changes: 19%
- Pruritus/rash.
- Dry skin.
No cerebellar toxicity observed.
Potential strengths:
- Dual antigen targeting.
- Broader antigen coverage.
- Potential reduction in antigen escape.
- Specifically studied extraosseous EMD.
Critique #1:
Single-center study. Entire cohort from China. External validity remains uncertain.
Need multicenter validation and broader demographics.
Critique #2:
Not as heavily pretreated as many US CAR-T populations:
Only:
- 84% prior anti-CD38 exposure.
- 38% prior autoSCT.
Could inflate efficacy compared with Western real-world cohorts.
Critique #3:
The major paradox:
- ORR 97%
- Median PFS only 5.8 months.
Dual targeting may improve initial tumor kill, but long-term persistence and EMD microenvironment resistance remain unresolved.
Key clinical question:
Could EMD require:
- Repeated immune pressure?
- CAR-T + maintenance?
- Sequential CAR/BsAb strategies?
- Novel microenvironment approaches?
Perhaps response induction isn’t the main problem anymore – durability is.
Take-home:
Dual-target BCMA/GPRC5D CAR-T may represent an important advance for EMD, but we should avoid equating deep initial responses with durable disease control.
The next frontier may be sustaining remission rather than achieving it.”
Title: Anti-BCMA/GPRC5D CAR T in relapsed or refractory multiple myeloma patients with extraosseous extramedullary disease
Authors: Dian Zhou, Yuekun Qi, Sha Ma, Qian Sun, Weiying Gu, Jieyun Xia, Xiaotian Zhang, Wei Chen, Hai Cheng, Kunming Qi, Feng Zhu, Fan Xia, Lili Zhu, Hujun Li, Huanxin Zhang, Dongmei Yan, Tingting Qiu, Yanlei Zhang, Shuixiu Peng, Wei Sang, Depeng Li, Alex H Chang, Bin Pan, Zhiling Yan
Other articles featuring Al-Ola A Abdallah on OncoDaily.