The Chronic Lymphocytic Leukemia Channel on VJHemOnc is an independent medical education platform, supported with funding from AstraZeneca (Diamond), AbbVie (Platinum), BeOne Medicines (Silver) and Lilly (Silver). Supporters have no influence on the production of content. The levels of sponsorship listed are reflective of the amount of funding given.
The Lymphoma Channel on VJHemOnc is an independent medical education platform, supported with funding from AstraZeneca (Diamond), BMS (Gold), Johnson & Johnson (Gold), Takeda (Silver) and Galapagos (Bronze). Supporters have no influence on the production of content. The levels of sponsorship listed are reflective of the amount of funding given.
SOHO 2024 | Pirtobrutinib as a bridge to CAR-T therapy in B-cell malignancies
Nirav Shah, MD, Medical College of Wisconsin, Milwaukee, WI, discusses the novel non-covalent BTK inhibitor, pirtobrutinib, and its efficacy across B-cell malignancies, particularly in diseases like mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL). He highlights its role as a bridge to CAR T-cell therapy, with promising early data showing potential improvements in the quality of T-cells. This interview took place at the Twelfth Annual Meeting of the Society of Hematologic Oncology (SOHO 2024) congress in Houston, TX.
These works are owned by Magdalen Medical Publishing (MMP) and are protected by copyright laws and treaties around the world. All rights are reserved.
Transcript
Pirtobrutinib is a novel, sort of first-in-class, non-covalent BTK inhibitor. So it’s a little bit different mechanistically than the BTK inhibitors we have to date, drugs like ibrutinib, zanubrutinib, acalabrutinib, which are all in a class of drugs called covalent inhibitors. They sort of irreversibly bind BTK. There was large data that came out that these drugs are, that pirtobrutinib is effective across B-cell malignancies, most effective in diseases like mantle cell lymphoma and chronic lymphocytic leukemia, but if you looked at the Phase I data, it actually showed efficacy across B-cell malignancies...
Pirtobrutinib is a novel, sort of first-in-class, non-covalent BTK inhibitor. So it’s a little bit different mechanistically than the BTK inhibitors we have to date, drugs like ibrutinib, zanubrutinib, acalabrutinib, which are all in a class of drugs called covalent inhibitors. They sort of irreversibly bind BTK. There was large data that came out that these drugs are, that pirtobrutinib is effective across B-cell malignancies, most effective in diseases like mantle cell lymphoma and chronic lymphocytic leukemia, but if you looked at the Phase I data, it actually showed efficacy across B-cell malignancies.
We know for patients who are trying to get to CAR T-cell therapy, disease control is really important going into CAR-T. We also know that CAR-T is logistically challenging, itcan sometimes take days, if not weeks, from the point in which you sort of think about CAR-T as an option to actually delivering the CAR-T cells. And so what we need for patients is a safe, effective way to manage and control their disease.
With the safety profile of pirtobrutinib, its ability to have sort of some efficacy across B-cell malignancies, we have used this agent sort of clinically as a bridge to CAR T-cell therapy. We shared some data at ASCO that actually showed that patients who got pirtobrutinib as a bridge actually saw some improvements in the quality of the T-cells that we actually produced as part of our ongoing clinical trials.
So taking this data together, we’ve developed a Phase I combination study of pirtobrutinib with a dual targeted 2019 CAR that our program has sort of been working with for many years. And we hope to launch that study soon. And we’re also going to be doing pirtobrutinib maintenance as a way to improve duration of response after CAR T-cell therapy. And so we think there’s benefit from a disease biology standpoint, but what we’re really excited to see in the prospective clinical trial is this pirtobrutinib and disease stabilization improve the fitness of the final CAR T-cell product. So I look forward to talking to you again, hopefully in a year or two when we have that data.
Read more...
