Although anti-CD19 chimeric antigen receptor T-cell (CAR-T)therapy has led to dramatic results in patients with hematological malignancieswho are seemingly out of treatment options, it is far from a panacea for allpatients, as a meaningful portion have disease that either never responds toCAR-T or eventually comes back after treatment with CAR-T.

To develop drugs for these patients who have exhausted yetanother treatment option, drug developers need to know how long these patientssurvive after CAR-T therapy so that they have historical controls in thepostCAR-T setting. These controls are thought to be the most useful asbenchmarks for future trials.

Not a lot is known as to what happens in the patients forwhom CAR-T therapy does not work, James Gerson, MD, assistant professor ofclinical medicine, Perelman School of Medicine, University of Pennsylvania,Philadelphia, told Cancer Therapy Advisor. Anecdotally, we say thatpatients often progress rapidly and arent able to get further therapies, butits not something theres a lot of data for.

With CAR-T therapy coming to the forefront as a treatmentoption, he said a lot of patients are going to get CAR-T therapy earlier onin their treatment course. As a result, drug discovery is most likely going tomove forward in the postCAR-T space because that will be the unmet need.

Researchers from Fred Hutchinson Cancer Research Center and Seattle Cancer Care Alliance, Washington, are helping address this unmet need, specifically for patients with chronic lymphocytic leukemia (CLL).

At the Transplantation & Cellular Therapy Meetings held in early 2020 in Orlando, Florida, these researchers reported the outcomes and characteristics of patients with CLL who received an investigational anti-CD19 CAR-T therapy during a clinical trial (ClinicalTrials.gov Identifier: NCT01865617), but either never had a response or eventually had disease relapse.1 The trial enrolled approximately 200 patients with CD19-expressing CLL, acute lymphoblastic leukemia, or non-Hodgkin lymphoma.

A total of 28 patients with CLL were included in the study,and among these, 16 (57%) had stable or progressive disease and 12 (43%)initially had a response after CAR-T therapy but then had disease relapse aftera median of 11 months.

Patients were retrospectively evaluated and found to havelived a median of 10.4 months after CAR-T therapy. Now we at least have anumber that tells you whats the expected survival if you were to have CAR T cells,said Premal Lulla, MBBS, assistant professor at the Center for Cell and GeneTherapy at Baylor College of Medicine and member of the Dan L DuncanComprehensive Cancer Center at Baylor College of Medicine, Houston, Texas,during an interview with Cancer Therapy Advisor.

Although he was not involved in the study, Dr Lulla saidlarge, multicenter analyses are needed to get a more comprehensive picture ofwhat happens to patients after CAR-T therapy fails.

The study also revealed 2 factors that were predictive ofoutcomes in this patient population. However, lead author Mazyar Shadman, MD,MPH, assistant member, clinical research division at Fred Hutchinson CancerResearch Center, Seattle, Washington, cautioned against overinterpretation ofthe data given that the study was retrospective and had a relatively smallsample size.

The first factor identified was the extent of treatment beforeCAR-T therapy. Specifically, patients whose disease progressed during treatmentwith ibrutinib and treatment with venetoclax before CAR-T therapy lived only amedian of 7 months after CAR-T therapy. In contrast, patients whose diseaseprogressed during treatment with only 1 of these drugs lived a median of 16.4months, an improvement that was determined to be statistically significant (P =.01).

See the original post here:
An Early Look at When CAR-T Therapy Fails Patients With CLL - Cancer Therapy Advisor

Comments are closed.