Cellular Therapies in Chronic Lymphocytic Leukemia and Richter’s Transformation: Recent Developments in Chimeric Antigen Receptor T-Cells, Natural Killer Cells, and Allogeneic Stem Cell Transplant
Abstract
:Simple Summary
Abstract
1. Introduction
2. What’s “New” in AlloHSCT for CLL and RT: Focus on Patients with Prior Novel-Agent Exposure
2.1. AlloHSCT in CLL
2.2. AlloHSCT for RT
2.3. AlloHSCT Limitations
3. CD19 CAR-T Therapies Approved in Other Indications
CAR-T Product | Approved Indication(s) | Construct | Studied in CLL and/or RT |
---|---|---|---|
Lisocabtagene maraleucel (Breyanzi) | Adult patients with relapsed(rel)/refractory(ref) large B-cell lymphoma including diffuse large B-cell lymphoma (DLBCL) NOS, including DLBCL arising from indolent lymphoma, high-grade B-cell lymphoma, primary mediastinal lymphoma, and follicular lymphoma (FL) grade 3B who are refractory to firstline chemoimmunotherapy or relapsed within 12 months, who are rel/ref after firstline and are ineligible for HSCT due to comorbidities or age, or rel/ref after two or more lines of systemic therapy [38,39] | Anti-CD19 4-1-BB CD3z CD4:CD8 1:1 | CLL [36,37,40] and RT [36,41] |
Tisagenlecleucel (Kymriah) | Adult patients with rel/ref DLBCL after two or more lines of systemic therapy, including DLBCL NOS, high grade B-cell lymphoma, and DLBCL arising from FL, adult patients with rel/ref FL after two or more lines of systemic therapy, and young patients (up to age 25) with refractory or in second or later relapse B-cell precursor acute lymphoblastic leukemia (ALL) [42,43,44] | Anti-CD19 4-1BB CD3z | CLL [7,45,46,47] |
Brexucabtagene autoleucel (Tecartus) | Patients with rel/ref mantle cell lymphoma and adult patients with relapsed or refractory B-cell precursor ALL [48,49] | Anti-CD19 CD28 CD3z Manufacturing step added to remove CD19 tumor cells | CLL [50] |
Axicabtagene ciloleucel (Yescarta) | Adult patients with large B-cell lymphoma that is refractory to firstline chemotherapy or that relapses within 12 months of firstline chemotherapy, adult patients with rel/ref large B-cell lymphoma after 2 or more lines of systemic therapy, including DLBCL NOS, primary media-stinal large B-cell lymphoma, and DLBCL arising from FL, and FL after 2 or more lines of systemic therapy [51,52,53] | Anti-CD19 CD28 CD3z | CLL [54] and RT [55] |
4. Emerging Strategies to Improve CAR-T Efficacy
4.1. Ibrutinib and Other Combinations
4.2. Novel CAR-T Targets and Constructs
4.3. Allogeneic CAR-T
4.4. Natural Killer CARs
4.5. CAR-T in Richter’s Transformation
5. Future Directions
6. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Coombs, C.C.; Easaw, S.; Grover, N.S.; O’Brien, S.M. Cellular Therapies in Chronic Lymphocytic Leukemia and Richter’s Transformation: Recent Developments in Chimeric Antigen Receptor T-Cells, Natural Killer Cells, and Allogeneic Stem Cell Transplant. Cancers 2023, 15, 1838. https://doi.org/10.3390/cancers15061838
Coombs CC, Easaw S, Grover NS, O’Brien SM. Cellular Therapies in Chronic Lymphocytic Leukemia and Richter’s Transformation: Recent Developments in Chimeric Antigen Receptor T-Cells, Natural Killer Cells, and Allogeneic Stem Cell Transplant. Cancers. 2023; 15(6):1838. https://doi.org/10.3390/cancers15061838
Chicago/Turabian StyleCoombs, Catherine C., Saumya Easaw, Natalie S. Grover, and Susan M. O’Brien. 2023. "Cellular Therapies in Chronic Lymphocytic Leukemia and Richter’s Transformation: Recent Developments in Chimeric Antigen Receptor T-Cells, Natural Killer Cells, and Allogeneic Stem Cell Transplant" Cancers 15, no. 6: 1838. https://doi.org/10.3390/cancers15061838