Frederick L. Locke, MD
Chimeric antigen receptor (CAR) T-cell therapy has shown durable responses in patients with subtypes of non-Hodgkin lymphoma; however, the key to optimizing responses is early referral, said Frederick L. Locke, MD.
“It's important that community oncologists realize that early referral for CAR T likely drives outcomes,” said Locke, a medical oncologist at Moffitt Cancer Center. “We need to get these patients to us earlier because of the time that is needed to set up the therapy. The more widespread that understanding is, the more lives will be saved by this therapy.”
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 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% remainining in response at a median follow-up of 15.4 months. 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 (ALL) 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.
In an interview during the 2018 OncLive®
State of the Science Summit™ on Hematologic Malignancies, Locke, one of the lead authors of ZUMA-1, discussed the expansion of CAR T-cell therapy in patients with lymphomas following the 2017 approval of axi-cel and remaining research questions with the therapy.
OncLive: You have been involved in the trials with axi-cel. What is it like to see its FDA approval?
: We now have 2 FDA-approved CAR T-cell products for the treatment of adult [patients with] aggressive B-cell lymphomas. It's been fantastic. We knew from single-center trials that tested CD19-directed CAR T-cell therapy that it could work for patients with B-cell malignancies. As we were running the phase I and then phase II ZUMA-I trial, we saw the greater than 80% response rate in patients who had very little chance for response or complete response. Those responses are durable. Over 40% of patients remain in remission 1 year out with almost a 1.5-year median follow-up. The results have been remarkable.
Transitioning it to real-world care has also been very rewarding. We're able to treat any patient who needs the therapy. One of the main things I wanted to get across to my colleagues is that it's key that these patients are referred early for consideration of CAR T-cell therapy. If I was a practicing oncologist treating many different diseases, and had a patient with aggressive lymphoma who progressed through frontline R-CHOP chemotherapy, I would already be thinking about referring that patient for CAR T-cell therapy. It takes time. It takes up to 4 weeks from the initial consult until the insurance approvals [come through] and [the cells are shipped and returned]. We want the patients to go to the centers that administer CAR T-cell therapy as soon as possible.
What else have clinical trials revealed about the therapy?
One of the key things we've learned is that it's OK to give bridging chemotherapy. In the ZUMA-I trial, we collected cells for [the] manufacturer of axi-cel and then waited for them to return. On average, it took 17 days. In both the JULIET trial and now the ongoing TRANSCEND trial with other CAR T-cell products for lymphoma, bridging chemotherapy was allowed.