Babis Andreadis, MD
Chimeric antigen receptor (CAR) T-cell therapy has activity in patients with relapsed diffuse large B-cell lymphoma (DLBCL), but there are a number of considerations to keep in mind before choosing to proceed with this treatment, explained Charalambos (Babis) Andreadis, MD, MSCE.
“It's something that we're very excited about, especially for patients with relapsed disease. We also need to remember that it doesn't work for everyone, and it's not available to everyone,” said Andreadis. “It’s limited by significant financial considerations and coverage. Even in the patient who can get it, it works about one-third of the time. There's still room for improvement of CAR T-cell therapy with either new CAR designs or with the addition of adjunctive treatments.”
In October 2017, the FDA approved the CD19-directed CAR T-cell therapy axicabtagene ciloleucel (axi-cel; Yescarta) for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after 2 or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma, and DLBCL arising from follicular lymphoma.
The approval was based on complete remission (CR) rates in the phase II ZUMA-I trial. Long-term follow-up data have since been shared showing an overall response rate of 82%, with 42% remaining in response at a median follow-up of 15.4 months.1 The median duration of response was 11.1 months (95% CI, 3.9-not estimable).
Axi-cel joined tisagenlecleucel (Kymriah), which, in August 2017, became the first FDA-approved CAR T-cell therapy. Tisagenlecleucel was initially approved for the treatment of patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia that is refractory or in second or later relapse. In May 2018, the FDA approved tisagenlecleucel for use in adult patients with relapsed/refractory large B-cell lymphoma—Including DLBCL not otherwise specified, high-grade B-cell lymphoma, and DLBCL arising from follicular lymphoma—after 2 or more lines of systemic therapy.
Lisocabtagene maraleucel (liso-cel; JCAR017) has also demonstrated efficacy. Updated data from the phase I TRANSCEND trial presented at the 2018 ASCO Annual Meeting showed that the CAR T-cell therapy had a durable CR rate of 46% at 6 months for patients with high-risk DLBCL.
In an interview during the 2018 OncLive®
State of the Science Summit™ on Hematologic Malignancies, Andreadis, associate professor of clinical medicine, Department of Medicine, University of California, San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center, discussed the use of CAR T-cell therapy in patients with DLBCL and the associated toxicities with each product, as well as other promising therapies in the paradigm.
OncLive: How has CAR T-cell therapy impacted patients with DLBCL?
: In the relapsed setting, DLBCL is still a disease in need of additional therapies. [Patients can do well with] transplant and may cure one-third of patients. There are a lot of patients who are ineligible for transplant or who don't respond well enough to chemotherapy to benefit from transplant. For those patients, we have CAR T-cell therapy, which can be active. My presentation focused on how we manage the toxicities of CAR T-cell therapies and how we triage patients for one or the other. Then, how we establish the production, efficacy, and toxicity of this treatment in the real-world setting.
Could you elaborate on the 2 FDA-approved CAR T-cell products?
There are 2 approved products now. One is tisagenlecleucel, which is a 4-IBB product. The other is axicabtagene-ciloleucel, which is a CD28 product. They have very similar activity, in my mind. The clinical trials that have been done show response rates in the 50% range and long-term responses in the 30% to 40% category. Those are the responses we're interested in because those are potentially the patients who can be cured.