Although anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapy has led to dramatic results in patients with hematological malignancies who are seemingly out of treatment options, it is far from a panacea for all patients, as a meaningful portion have disease that either never responds to CAR-T or eventually comes back after treatment with CAR-T.
To develop drugs for these patients who have exhausted yet another treatment option, drug developers need to know how long these patients survive after CAR-T therapy so that they have historical controls in the post–CAR-T setting. These controls are thought to be the most useful as benchmarks for future trials.
“Not a lot is known as to what happens in the patients for whom CAR-T therapy does not work,” James Gerson, MD, assistant professor of clinical medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, told Cancer Therapy Advisor. “Anecdotally, we say that patients often progress rapidly and aren’t able to get further therapies, but it’s not something there’s a lot of data for.”
With CAR-T therapy coming to the forefront as a treatment option, he said “a lot” of patients are going to get CAR-T therapy earlier on in their treatment course. As a result, drug discovery is most likely going to move forward in the post–CAR-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 after a median of 11 months.
Patients were retrospectively evaluated and found to have lived a median of 10.4 months after CAR-T therapy. “Now we at least have a number that tells you what’s the expected survival if you were to have CAR T cells,” said Premal Lulla, MBBS, assistant professor at the Center for Cell and Gene Therapy at Baylor College of Medicine and member of the Dan L Duncan Comprehensive 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 said large, multicenter analyses are needed to get a more comprehensive picture of what happens to patients after CAR-T therapy fails.
The study also revealed 2 factors that were predictive of outcomes in this patient population. However, lead author Mazyar Shadman, MD, MPH, assistant member, clinical research division at Fred Hutchinson Cancer Research Center, Seattle, Washington, cautioned against overinterpretation of the data given that the study was retrospective and had a relatively small sample size.
The first factor identified was the extent of treatment before CAR-T therapy. Specifically, patients whose disease progressed during treatment with ibrutinib and treatment with venetoclax before CAR-T therapy lived only a median of 7 months after CAR-T therapy. In contrast, patients whose disease progressed during treatment with only 1 of these drugs lived a median of 16.4 months, an improvement that was determined to be statistically significant (P =.01).