On Wednesday 27 March 2019, Oral Session 20 (OS20) took place at the 45th Annual Meeting of the European Society of Blood and Marrow Transplantation (EBMT), Frankfurt, DE. During that session, Abstract OS20-2 was presented by Yongxian Hu from Zhejiang University, Hangzhou, CN.
In an attempt to improve the response rates and lower the toxicity with chimeric antigen receptor T-cell (CAR-T) therapy in B-cell non-Hodgkin lymphoma (B-NHL), the preliminary clinical evaluation of a dual targeting CD19 and CD22 CAR-T construct was presented here. The primary aim of this study was to assess the safety of the dual CAR-T construct. The investigators also compared the efficacy of the dual CAR-T construct to a single-targeting CD19 CAR-T construct. The cytotoxicity of the dual CAR-T construct was assessed in vitro and in mouse models in vivo prior to this in-human preliminary trial.
Study design & baseline characteristics
- N = 20 heavily pre-treated patients with B-cell lymphoma infused with either:
- CD19/CD22 dual CAR-T construct: n = 11
- CD19 CAR-T construct: n = 9
- Dual CAR-T construct structure:
- CAR with antigen recognition domains of both CD19 (anti-CD19 ScFv) and CD20 (anti-CD22 ScFv)
- 4-1BB costimulatory domain
- CD3z signaling domain
- Lymphodepletion:
- Fludarabine (Flu): 30 mg/m2 1−3 days prior to CAR-T infusion
- Cytoxan (CTX): 500 mg/m2 2−3 days prior to CAR-T infusion
- Peripheral blood mononuclear cell (PBMC) collection for CAR-T engineering occurred approximately 11 days prior to infusion
- Computed tomography (CT) or positron emission tomography (PET)-CT was used for disease assessment every 30 days following CAR-T infusion
- No statistically significant differences in baseline characteristics between the single CD19 CART and the dual CD19/CD22 CAR-T groups:
| Characteristic | CD19 single CAR-T group (N = 9) | Dual CD19/CD22 CAR-T group (N = 11) |
| Median age (range) | 47.8 (27−65) years | 45.6 (25−65) years |
| Male patients | 55.6% | 54.5% |
| Disease type | ||
| DLBCL | 88.9% | 81. 8% |
| Burkitt lymphoma | 0% | 9.1% |
| SLL/CLL | 11.1% | 0% |
| Lymphoblastic lymphoma | 0% | 9.1% |
| Prior lines of treatment | ||
| 2−3 | 22.2% | 27.2% |
| 4−5 | 33.3% | 36.3% |
| > 5 | 44.4% | 36.3% |
| Disease stage | ||
| I−II | 22.2% | 18.2% |
| III−IV | 77.8% | 81.8% |
| Refractory status at study entry | ||
| Primary refractory | 44.4% | 36.4% |
| Refractory to ≥ 2 lines | 55.6% | 63.6% |
| Relapse after auto-SCT | 22.2% | 18.2% |
Key results
- Average CAR-T cell infusion dose (range):
- CD19/CD22 dual CAR-T group: 5.2 x 106/kg (1.1−10 x 106/kg)
- CD19 CAR-T group: 5.8 x 106/kg (1.6−10 x 106/kg)
- Comparison: P > 0.05
- Average peak CAR-T cell expansion after infusion (10.1 ± 3.32 and 9.2 ± 2.25 days):
- CD19/CD22 dual CAR-T group: 68.7% (6.9−78.6% in CD3+ T cells)
- CD19 CAR-T group: 36.8% (3.6−60.9% in CD3+ T cells)
- Grade 3−5 cytokine release syndrome (CRS):
- CD19/CD22 dual CAR-T group: 10%
- CD19 CAR-T group: 33%
- Neurotoxicity occurred in one patient infused with the dual CD19/CD22 CAR-T construct
- No patient died due to CAR-T-related adverse events
- Overall response rates (ORR):
- CD19/CD22 dual CAR-T group: 90%
- CD19 CAR-T group: 75%
- CR rates:
- CD19/CD22 dual CAR-T group: 70%
- CD19 CAR-T group: 50%
- Overall survival rates at Day 90 post infusion:
- CD19/CD22 dual CAR-T group: 90.0 ± 9.5%
- CD19 CAR-T group: 55.6% ± 16.6%
- The OS rates remain stable at Day 250 post infusion
Conclusions
Promising preliminary in-human results for the dual CD19/CD22 CAR-T construct with B-NHL patients achieving higher CR and ORR, with low severe CRS rates, compared to the standard CD19 single CAR-T construct. More in-human studies and of a larger scale with extended observation periods are needed to further validate these preliminary results.
Source:
-
Hu Y. et al. Novel CD19/CD22 dual targeting CAR-T cells have prominent anti-tumor activity against relapsed/refractory B-cell lymphoma. Abstract OS20-2: 45th EBMT Annual Meeting, Frankfurt, Germany
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Wow that was odd. I just wrote an very long comment but after I clicked submit my comment didn’t show up. Grrrr… well I’m not writing all that over again. Anyways, just wanted to say wonderful blog!
At this time it appears like Drupal is the top blogging platform available right now. (from what I’ve read) Is that what you’re using on your blog?
Right now it looks like Drupal is the best blogging platform available right now. (from what I’ve read) Is that what you’re using on your blog?
Wow that was unusual. I just wrote an very long comment but after I clicked submit my comment didn’t appear. Grrrr… well I’m not writing all that over again. Regardless, just wanted to say great blog!
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Wow that was strange. I just wrote an incredibly long comment but after I clicked submit my comment didn’t appear. Grrrr… well I’m not writing all that over again. Anyways, just wanted to say wonderful blog!
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At this time it sounds like WordPress is the preferred blogging platform out there right now. (from what I’ve read) Is that what you are using on your blog?
At this time it appears like Drupal is the best blogging platform out there right now. (from what I’ve read) Is that what you’re using on your blog?
Currently it seems like Movable Type is the best blogging platform available right now. (from what I’ve read) Is that what you are using on your blog?
Aw, this was a very nice post. Finding the time and actual effort to make a very good article… but what can I say… I put things off a whole lot and don’t seem to get nearly anything done.
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Hey I know this is off topic but I was wondering if you knew of any widgets I could add to my blog that automatically tweet my newest twitter updates. I’ve been looking for a plug-in like this for quite some time and was hoping maybe you would have some experience with something like this. Please let me know if you run into anything. I truly enjoy reading your blog and I look forward to your new updates.
Wow that was unusual. I just wrote an very long comment but after I clicked submit my comment didn’t appear. Grrrr… well I’m not writing all that over again. Anyhow, just wanted to say excellent blog!
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Hey I know this is off topic but I was wondering if you knew of any widgets I could add to my blog that automatically tweet my newest twitter updates. I’ve been looking for a plug-in like this for quite some time and was hoping maybe you would have some experience with something like this. Please let me know if you run into anything. I truly enjoy reading your blog and I look forward to your new updates.
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Aw, this was a very good post. Finding the time and actual effort to generate a top notch article… but what can I say… I procrastinate a whole lot and don’t seem to get anything done.
Have you ever thought about including a little bit more than just your articles? I mean, what you say is important and everything. However think of if you added some great photos or videos to give your posts more, “pop”! Your content is excellent but with pics and clips, this website could certainly be one of the most beneficial in its field. Wonderful blog!
I love reading through an article that will make men and women think. Also, many thanks for allowing for me to comment!
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At this time it seems like WordPress is the best blogging platform available right now. (from what I’ve read) Is that what you’re using on your blog?
Hey I know this is off topic but I was wondering if you knew of any widgets I could add to my blog that automatically tweet my newest twitter updates. I’ve been looking for a plug-in like this for quite some time and was hoping maybe you would have some experience with something like this. Please let me know if you run into anything. I truly enjoy reading your blog and I look forward to your new updates.
Hey I know this is off topic but I was wondering if you knew of any widgets I could add to my blog that automatically tweet my newest twitter updates. I’ve been looking for a plug-in like this for quite some time and was hoping maybe you would have some experience with something like this. Please let me know if you run into anything. I truly enjoy reading your blog and I look forward to your new updates.
Currently it sounds like WordPress is the top blogging platform available right now. (from what I’ve read) Is that what you’re using on your blog?
Wow that was strange. I just wrote an extremely long comment but after I clicked submit my comment didn’t appear. Grrrr… well I’m not writing all that over again. Anyway, just wanted to say wonderful blog!
At this time it looks like WordPress is the preferred blogging platform available right now. (from what I’ve read) Is that what you’re using on your blog?
Aw, this was an extremely good post. Taking a few minutes and actual effort to make a good article… but what can I say… I procrastinate a whole lot and never manage to get nearly anything done.
May I just say what a comfort to discover someone that genuinely understands what they are discussing on the internet. You actually understand how to bring a problem to light and make it important. More people must read this and understand this side of the story. I can’t believe you’re not more popular since you definitely possess the gift.
Aw, this was a very good post. Taking a few minutes and actual effort to produce a good article… but what can I say… I procrastinate a lot and never manage to get anything done.
Hi there, You have performed an excellent job. I will definitely digg it and in my opinion recommend to my friends. I am sure they will be benefited from this website.
Right now it appears like BlogEngine is the top blogging platform available right now. (from what I’ve read) Is that what you are using on your blog?
Hey I know this is off topic but I was wondering if you knew of any widgets I could add to my blog that automatically tweet my newest twitter updates. I’ve been looking for a plug-in like this for quite some time and was hoping maybe you would have some experience with something like this. Please let me know if you run into anything. I truly enjoy reading your blog and I look forward to your new updates.
Hey I know this is off topic but I was wondering if you knew of any widgets I could add to my blog that automatically tweet my newest twitter updates. I’ve been looking for a plug-in like this for quite some time and was hoping maybe you would have some experience with something like this. Please let me know if you run into anything. I truly enjoy reading your blog and I look forward to your new updates.
At this time it sounds like Movable Type is the best blogging platform available right now. (from what I’ve read) Is that what you’re using on your blog?