One patient was still in response more than five years after a single infusion. For chronic lymphocytic leukemia, a disease that normally means treatment for life, that is an unusual sentence to write.
It comes from Tanya Siddiqi of City of Hope, an investigator on TRANSCEND CLL 004, the trial behind the first CAR-T therapy cleared for CLL. “CLL is not typically a curable condition,” she told Healio, “but we are trying to get more patients moving toward a potential cure using CAR T cells.”
What the FDA approved
In March 2024 the US Food and Drug Administration gave accelerated approval to Breyanzi (lisocabtagene maraleucel), sold by Bristol Myers Squibb. It covers adults whose CLL or small lymphocytic lymphoma has returned or resisted treatment, after at least two earlier lines that included a BTK inhibitor as well as a BCL-2 inhibitor. Bristol Myers Squibb called it the first CAR T for these patients, noting that earlier attempts with other cell therapies had met little success.
The decision rested on the phase 1/2 trial’s 65 patients who could be evaluated for efficacy. Their median age was 66, and they had been through a median of 5 prior therapies. Most had high-risk disease: 43% carried a del(17p) change and 62% a complex karyotype.
Twenty percent reached a complete response. The overall response rate was 45%, with a median duration of response of 35.3 months. The first response typically arrived after 1.1 months. Among the patients with a complete response, 100% were still responding at 12 months and 87.5% at 18 months.
The earlier Lancet results
Results published earlier in The Lancet, covering 117 adults, used a different yardstick. In the 87-patient full efficacy group, 18% achieved complete remission, or complete remission with incomplete marrow recovery. That was about three times the rate seen in historical controls, and it met the trial’s primary endpoint. Siddiqi called the findings in patients who had failed a BTK inhibitor and venetoclax “highly statistically significant.” In that subgroup of 49, median progression-free survival was 11.9 months and median overall survival 30.3 months.
Cost to the patient
This is a heavy therapy. In the 89 patients assessed for safety, 60% had serious toxicities and 1.1% had a fatal adverse event. Cytokine release syndrome occurred in 83%, with grade 3 or worse in 9%. Encephalopathy affected 44%, and 18% of those cases were grade 3 or higher. Siddiqi explained the reactions are more frequent in CLL than in lymphoma because the leukemia cells circulate in the blood. Five treatment-related deaths occurred in the Lancet analysis; investigators tied one, from macrophage activation syndrome, to the drug.
Early real-world signal
At ASCO 2026, researchers reported registry data from the CIBMTR on 59 patients who received Breyanzi in everyday practice from May 2024 through the end of 2025. The overall response rate was 83% and the complete response rate 55%. Of 22 complete responders who had residual disease testing, 18 were negative. Oncologist Emily Tomasulo, who reviewed the data, said the results exceeded expectations.
Sources
- FDA Approves Lisocabtagene Maraleucel for Relapsed or Refractory CLL or SLL | OncLive
- CAR-T may move more patients with CLL 'toward a potential cure' | Healio
- CAR-T may move more patients with CLL 'toward a potential cure' | Healio (part 2)
- A CAR-T Therapy Is Working Better Than Expected for Patients With Hard to Treat Leukemia | CURE
