Mark Leick, MD, physician investigator, CCR Group C Monthly, Massachusetts General Research Institute, assistant professor, medicine, Harvard Medical School, assistant in medicine, Medicine-Hematology/Oncology, Massachusetts General Hospital, discusses the challenges and limitations associated with the use of CAR T-cell therapy across hematologic malignancies, highlighting how ongoing research may potentially ameliorate present unmet needs.

The development of CAR T-cell therapy has become a unified endeavor, with multiple companies dedicating resources to this field, Leick begins. However, the logistical aspects of administering this therapy poses a significant challenge, he says. CAR T-cell therapy is custom-manufactured for individual patients, with the exception of some clinical trials. This process involves collecting the patient's T-cells, sending them for manufacturing, and then returning them for subsequent treatment, Leick details. The variation in T cell behavior can present a substantial challenge. Moreover, the costs involved in manufacturing CAR T-cell therapy can create difficulties in terms of payments and insurance approval, Leick adds.

Another limitation with the use of CAR T-cell therapy lies in extending its use to other disease types, Leick continues. Although efforts are underway to address this need, the therapy has not yet proven as effective when treating solid tumors, Leick explains. Nonetheless, advancements in this area could yield positive outcomes in the near future, Leick says. Notably, investigators at Stanford University have achieved promising results by using CAR T-cell therapy to treat diffuse intrinsic pontine glioma, a pediatric brain tumor, he describes, adding that further research and collaboration are necessary to achieve this outcome, Leick states.

Lastly, researchers are striving to develop allogeneic CAR T-cell products that can be readily administered to patients without customization-related manufacturing delays, Leick says. This approach could resemble the current model of blood donation, where standardized products can be readily used, Leick continues. The use of modern genetic technologies to prevent complications such as cross tolerance and graft-vs-host disease could increase the efficacy of allogeneic CAR T-cell therapies across a broader group of individuals. Although progress is being made, additional work and refinement are needed to overcome these obstacles and make allogeneic CAR T-cell therapy a viable option, Leick concludes.

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Mark Leick, MD, discusses the challenges and limitations associated with the use of CAR T-cell therapy across hematologic malignancies, highlighting how ongoing research may potentially ameliorate present unmet needs.

Dr Leick on Limitations Associated With CAR T-Cell Therapy in Hematologic Malignancies

Mark Leick, MD, physician investigator, CCR Group C Monthly, Massachusetts General Research Institute, assistant professor, medicine, Harvard Medical School, assistant in medicine, Medicine-Hematology/Oncology, Massachusetts General Hospital, discusses the varying role of CAR T-cell therapy across various hematologic malignancies, elaborating on the cause of its effectiveness in these disease spaces.

CAR T-cell therapies are designed to target tumor-specific antigens, Leick begins, stating that the most common target is CD19. This marker is found on B-cells and is expressed in a variety of lymphomas. The success of this drug class has been notable in B-cell malignancies including acute lymphoblastic leukemia and diffuse large B-cell lymphoma, leading to initial approvals in both disease types, Leick says.

Over time, the use of CAR T-cell therapy has expanded to other B-cell lymphomas such as mantle cell lymphoma or follicular lymphoma, the latter of which is considered less aggressive, Leick describes. Notably, there have been 2 FDA approvals for CAR T-cell therapy in relapsed/refractory multiple myeloma: 

idecabtagene vicleucel (Abecma) was approved in March, 2021

iltacabtagene autoleucel (Carvykti) was approved in February, 2022

. Both are currently used for the treatment of patients whose disease has progressed on 4 or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.

The key to this success lies in the fact that CD19 is expressed on normal B cells in the body, which are not essential for survival, Leick explains. Patients can therefore receive artificial replacements for the immunoglobulins produced by B cells, allowing them to function normally without these cells, he adds.

This targeted approach has enabled CAR T-cell therapy to address a wide spectrum of cancers associated with B cells while minimizing the impact on essential bodily functions, Leick states. Ultimately, these outcomes reflect the precision and adaptability of this treatment modality, he concludes.

Mark Leick, MD, discusses the varying role of CAR T-cell therapy across various hematologic malignancies, elaborating on the cause of its effectiveness in these disease spaces.
 

Mark Leick, MD

Articles

Dr Leick on Limitations Associated With CAR T-Cell Therapy in Hematologic Malignancies

Dr Leick on the Use of CAR T-Cell Therapy Across Hematologic Malignancies