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SAN DIEGO -- A majority of patients with relapsed and refractory lymphoma or leukemia obtained durable remissions following treatment with chimeric antigen receptor (CAR) T-cell therapy, according to studies reported here.

Two-thirds of children and young adults with acute lymphoblastic leukemia (ALL) who attained complete responses with tisagenlecleucel (Kymriah) remained in remission at 18 months. Overall, 70% of 79 patients followed for at least 3 months were alive at 18 months, reported Stephan A. Grupp, MD, PhD, of the Children's Hospital of Philadelphia, at the American Society of Hematology (ASH) annual meeting.

In a separate study at ASH, and simultaneously publishing in the , more than half of 99 patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) achieved objective responses with tisagenlecleucel, including 40% with a complete remission. Two-thirds of the patients initially in complete response maintained that status, said Richard Thomas Maziarz, MD, of Oregon Health & Science University Knight Cancer Center in Portland.

"The longer-term follow-up is very exciting to us," Grupp said during an ASH press conference. "It indicates there are a group of patients, most of whom do not go on to transplant, [for whom] this is a therapy that has potential for long-term disease control. Among all patients who were infused, we're seeing excellent overall survival [OS]."

Exploratory studies with an investigational next-generation sequencing (NGS) assay for minimal residual disease (MRD) showed that 80% of patients with a negative MRD result after attaining remission remained in remission long term, as compared with 20% of patients who had a positive NGS result.

"As we think about the role of transplant, this is a group of patients that I'm wondering whether they really need a transplant, and the vast majority of them did not get one," Grupp added.

The report on the ALL population represented an update that led to initial FDA approval of tisagenlecleucel. The study involved patients (ages 3 to 21) with bone marrow blasts ≥5. They received a single CAR T-cell infusion, and the trial had a primary endpoint of overall remission rate at 3 months.

The initial report from the trial came after a median follow-up of 24 months. Grupp's presentation covered a 35-month median follow-up.

Treatment with tisagenlecleucel led to complete responses (with and without complete hematologic recovery) in 82% of the patients, and 66% of that subgroup remained in complete remission at 18 months. Relapse-free survival among responding patients was 66% at 12 and 18 months and 62% at 24 months. The 12- and 18-month OS was 76% and 70%, respectively.

"Relapse looks a lot like relapse after a transplant," said Grupp. "If you're not relapsing after a year or two, the likelihood of that happening is a lot lower. Most relapses occur during the first year."

The adverse event profile has changed little over time. Three-fourths of patients developed cytokine release syndrome (CRS, managed with a protocol developed specifically for patients treated with CAR T-cell therapy), 43% had infections, 42% had cytopenias that persisted >28 days, 39% had neurologic events (no cerebral edema), and 5% had tumor lysis syndrome (TLS). Grade 3/4 events included CRS in 49% of patients, infections in 24%, persistent cytopenias in 36%, neurologic events in 13%, and TLS in 5%. Most adverse events occurred during the first 8 weeks after infusion, said Grupp.

The update of the DLBCL study is important because of inherent features of clinical trial design.

"When you look at early data, you always worry about selection bias," he said. "You pick the best patients, and that doesn't represent real life. As you move into a median follow-up of 19 months, you are looking at the real natural history of this disease. These are patients with multiple-relapse, refractory large-cell lymphoma."

The initial data analysis occurred after a median follow-up of 14 months. With an additional 5 months added to the median duration of follow-up, the data showed that 54% of the patients responded to tisagenlecleucel, including a 40% rate of complete remission. Additionally, half of patients who had partial responses subsequently converted to complete response, said Maziarz. Responses were observed across all DLBCL subgroups.

The median duration of response had yet to be reached. Median OS was 11.1 months for all patients who received tisagenlecleucel. Median survival could not be calculated for patients who attained complete responses.

The type and frequency of adverse events were similar to those observed in the ALL study. However, less grade 3/4 toxicity occurred, including CRS (23%), prolonged cytopenia (34%), infections (19%), neurologic events (11%), febrile neutropenia (15%), and TLS (2%). No treatment-related deaths occurred.