All content on this site is intended for healthcare professionals only. By acknowledging this message and accessing the information on this website you are confirming that you are a Healthcare Professional. If you are a patient or carer, please visit the Lymphoma Coalition.
Introducing
Now you can personalise
your Lymphoma Hub experience!
Bookmark content to read later
Select your specific areas of interest
View content recommended for you
Find out moreThe Lymphoma Hub website uses a third-party service provided by Google that dynamically translates web content. Translations are machine generated, so may not be an exact or complete translation, and the Lymphoma Hub cannot guarantee the accuracy of translated content. The Lymphoma Hub and its employees will not be liable for any direct, indirect, or consequential damages (even if foreseeable) resulting from use of the Google Translate feature. For further support with Google Translate, visit Google Translate Help.
The Lymphoma & CLL Hub is an independent medical education platform, sponsored by Beigene and Roche, and supported through educational grants from Bristol Myers Squibb, Ipsen Biopharmaceuticals, Lilly, Pfizer, and Pharmacyclics LLC, an AbbVie Company and Janssen Biotech, Inc., administered by Janssen Scientific Affairs, LLC View funders.
Bookmark this article
During iwCLL, on 15th May 2017, the “Additional Therapies for the Relapsed/Refractory CLL Patient” session took place and was co-chaired by Michael Keating (MD Anderson Cancer Center) and Jacqueline Barrientos (The Feinstein Institute for Medical Research).
“Anti-CD19 CAR-T Cell Therapy With Defined T-Cell Subsets for Ibrutinib-Refractory CLL” was a presentation given during this session by David G. Maloney, MD, PhD, from the Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Maloney began by explaining that CAR-T cells produced from distinct T-cell subsets differ in potency. NSG mice bearing Raji tumors (0.5x106 tumor cell inoculation; day 0) were treated with human CAR-T cells manufactured from distinct T-cell subsets (on day 7). CAR-T cells produced from CD8+ TCM cells were highly potent (Sommermeyer et al. 2015).
Engineering selected T-cell subsets could enhance potency and allow delivery of the same cell product in all patients, potentially providing more uniform data on dose response and toxicity.
Pre-clinical studies have established that a defined composition of CD8+ TCM derived and CD4+ derived CAR T-cells provides optimal potency.
The talk then focused on the outline of the phase I/II study of JCAR014 in adult B-cell ALL, NHL, and CLL patients (NCT01865617).
As of 9/1/16, 136 patients had been treated: ALL = 48, NHL = 64, and CLL = 24.
Dose Level |
Cells/kg |
---|---|
1 |
2x105 EGFRt+ |
2 |
2x106 EGFRt+ |
3 |
2x107 EGFRt+ |
Lymphodepletion and JCAR014 immunotherapy in high-risk CLL patients:
Treatment |
N=24 |
---|---|
Lymphodepleting chemotherapy |
|
Cyclophosphamide/fludarabine (Cy/Flu) |
21 (87%) |
Non-Cy/Flu |
3 (13%) |
CAR-T cell manufacturing |
|
CD8+ central memory and CD4+ |
7 (29%) |
CD8+ all subsets and CD4+ |
17 (71%) |
CD19 CAR-T cell dose level |
|
DL1 (2x105 EGFRt+ cells/kg) |
4 (17%) |
DL2 (2x106 EGFRt+ cells/kg) |
19 (79%) |
DL3 (2x107 EGFRt+ cells/kg) |
1 (4%) |
Cycles |
|
Single cycle |
18 (75%) |
Outpatient lymphodepletion and CAR-T cells |
18 (75%) |
Second cycle for residual disease or relapse |
6 (25%) |
Maloney then asked “can IGH sequencing of the marrow at 4 weeks after JCAR014 identify patients with better outcomes?”
Additionally, higher JCAR014 counts in the blood after infusion were associated with better bone marrow response in high-risk CLL. Patients with a higher peak CD3+/EGFRt+ CAR-T cell count in the blood had a reduced hazard of progression or death (HR, 0.56; 95% CI, 0.34–0.93; P = 0.025).
Maloney concluded that in high-risk CLL patients CD19 CAR-T cells of defined composition (JCAR014) can be administered with an acceptable early toxicity profile. JCAR014 and Cy/Flu lymphodepletion shows a high-level or anti-tumor activity as measured by:
Deep marrow clearance by IGHseq after JCAR014 provides early signs of durable responses with 100% PFS and OS.
Lastly, Maloney presented evidence that ROR1 presents as a novel target for CAR-T cell therapy for CLL, MCL, and solid tumors as it is highly expressed on the surface of malignant B-cells:
Understanding your specialty helps us to deliver the most relevant and engaging content.
Please spare a moment to share yours.
Please select or type your specialty
Your opinion matters
Subscribe to get the best content related to lymphoma & CLL delivered to your inbox