CAR T-Cell Therapy

Non-Hodgkin Lymphoma

Marcelo C. Pasquini, MD, discusses the rationale for analyzing real-world data for the use of tisagenlecleucel, a chimeric antigen receptor T-cell therapy, as a treatment for patients with acute lymphoblastic leukemia and diffuse large B-cell lymphoma. This CD19 CAR T cell was approved 2 years ago for use in both ALL and DLBCL.

Now in it 24th year, the annual International Congress on Hematologic Malignancies: Focus on Leukemias, Lymphomas, and Myeloma, hosted by Physicians’ Education Resource, LLC, continues to bring significant advances in hematology to the forefront.

To improve the efficacy of chimeric antigen receptor T-cell therapies, Nirali N. Shah, MD, MHSc, suggested including new constructs that target more than 1 antigen in patients with acute lymphoblastic leukemia, during a presentation at the 2019 SOHO Annual Meeting.<br /> &nbsp;

In an interview with&nbsp;Targeted Oncology, Sattva S. Neelapu, MD, discussed the evolving role for CAR T-cell therapy in patients with B-cell lymphomas. He also highlighted the toxicities commonly associated with these therapies and how physicians can treat these AEs as they arise.

The initial pilot study of CTL019 in heavily pretreated CD19-positive hematologic malignancies demonstrated the feasibility of CAR T-cell therapy in patients with CLL. A presentation at the 2019 American Society of Gene &amp; Cell Therapy Annual Meeting reported 2 cases of chemotherapy-resistant CLL, with ongoing follow- up at 8 years showing persistence of CAR-engineered T cells and sustained remission, as determined by flow cytometry and deep sequencing of immunoglobulin H rearrangements.&nbsp;

In an interview with <em>Targeted Oncology</em>, Chong, a fellow at the University of Pennsylvania, discussed the 4-year follow-up data for CAR T cells in patients with DLBCL and FL. She also addressed the challenges that need to be overcome in order to give more patients access to this type of therapy.

In the phase I/II TRANSCEND CLL 004 study, chimeric antigen receptor T-cell therapy lisocabtagene maraleucel led to undetectable minimal residual disease in patients with relapsed/refractory chronic lymphocytic leukemia.

Kieron Dunleavy, MD, discussed current approaches to treating patients with MCL, highlighting peer discussions on the subject and information about the ZUMA-2 trial, in an interview with&nbsp;<em>Targeted Oncology</em>.

The FDA has granted an orphan drug designation to MB-102, a CD123-directed CAR T-cell therapy, for the treatment of patients with acute myeloid leukemia.

Significant activity was observed when ibrutinib was administered concurrently with CD19-directed CAR T-cell therapy compared with separately in patients with&nbsp;high-risk relapsed/refractory chronic lymphocytic leukemia who had progressed on or were intolerant of ibrutinib.&nbsp;Data presented at the 15th International Conference on Malignant Lymphoma show a high response rate with this concurrent treatment.&nbsp;

The FDA has granted P-BCMA-101 with an orphan drug designation for the treatment of patients with relapsed and/or refractory multiple myeloma.

A discussion between&nbsp;regulators and special interest groups has cooled some of the excitement generated by the emergence of chimeric antigen receptor T-cell therapy for treating hematologic cancers.

Frederick L. Locke, MD, discusses how chimeric antigen receptor (CAR) T-cell therapies have evolved over the last 30 years of research in the field of hematologic malignancies.

The success of chimeric antigen receptor T-cell therapy observed in hematologic malignancies has not yet translated into the solid tumor setting; however, efforts continue to try to bring this new modality into the treatment paradigm for solid tumors, including pancreatic cancer.&nbsp;

In data presented at the 2018 ASH Annual Meeting,&nbsp;bispecific T-cell engager antibody constructs demonstrated encouraging activity in patients with&nbsp;multiple myeloma and acute myeloid leukemia.

According to results from a small clinical study, checkpoint&nbsp;inhibitors in combination with&nbsp;chimeric antigen receptor T-cell therapy showed promise for improving CAR T-cell persistance in some patients with relapsed B-cell acute lymphoblastic leukemia. &nbsp; &nbsp;&nbsp;<br /> &nbsp;

Patients with&nbsp;acute lymphoblastic leukemia saw a reduction in the risk for recurrence after receiving a stem cell transplant for the first time following treatment with CD19 chimeric antigen receptor T-cell therapy.

According to a retrospective phase I/II study, over 80% of patients with relapsed or refractory chronic lymphocytic leukemia responded to concurrent treatment with ibrutinib and the CD19-targeted chimeric antigen receptor CAR T-cell therapy, JCAR014.¹ Findings from this study were presented at&nbsp;the 60th American Society of Hematology Annual Meeting.