The early study of the investigational CAR-T cell therapy lisocabtagene maraleucel shows how patients with relapsed/refractory CLL/SLL may have a viable new treatment option.
In high-risk patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), lisocabtagene maraleucel (liso-cel) treatment resulted in a high rate of undetectable minimal residual disease (uMRD) with rapid and durable responses, according to updated follow-up results of the ongoing TRANSCEND CLL 004 study presented at the 2020 ASH Annual Meeting and Exposition.
The phase 1/2 trial examining liso-cel, the investigational chimeric antigen receptor (CAR)-T cell therapy, enrolled a total of 23 patients with R/R CLL or SLL. All were evaluable for safety profiles of liso-cel, while 22 were evaluable for efficacy.
The median age of patients on the trial was 66 years old; all patients had undergone a median of 6 prior therapies; and 83% of patients had high-risk disease. All 23 patients had previously received Imbruvica (ibrutinib), but 91% were refractory to, or relapsed on, Imbruvica and two patients were intolerant to ibrutinib. Forty-eight percent of patients were refractory to both a prior BTK inhibitor and Venclexta (venetoclax).
“For patients who had failed both BTK inhibition and venetoclax prior to enrolling onto our study, the baseline disease characteristics of those 11 patients were fairly similar to the monotherapy total cohort of 23 patients,” explained lead author Dr. Tanya Siddiqi, M.D., in a presentation at ASH.
At the 15-month follow up and the 18-month follow up, researchers found responses were maintained by 53% and 50% of patients respectively. However, at a median follow up of 18 months, the median duration of response was not reached in patients who had initially responded to liso-cel, and median progression-free survival (PFS) was 18 months.
MRD, the number of leukemic cells that remain in the patient during treatment, was assessed in the patient’s blood by flow cytometry, with 20 of the 23 patients being MRD evaluable. Fifteen patients had uMRD in the blood while 13 had uMRD in their bone marrow. Sixty percent of patients achieved uMRD by day 30 of treatment with liso-cel.
Siddiqi, a hematologist oncologist at the City of Hope, went on to note that lico-cel therapy elicited rapid, deep and durable responses and highlighted how, after a 24-month follow up, all seven patients who completed the two-year study maintained their response.
“These responses appear to be durable over time. At the 12-month mark, 50% of patients were in response and only 2 of these responders progressed beyond the 12-month mark,” Siddiqi said in her presentation.
Additionally, researchers found the safety profile of liso-cel to be in line with previously reported outcomes, with no late or delayed side effects emerging during the 2-year follow-up.
However, three patients experienced Richter’s transformation during treatment, an event that changes the CLL cells over time when patients are refractory to treatment making responses harder. The most common side effects encountered during treatment were grade 3/4 and included low platelet levels (70%), anemia (78%), neutropenia (57%) and leukopenia (43%) a reduction in the number of white blood cells.
Overall, patients in this heavily pretreated, high-risk population who were treated withliso-cel had a high rate of uMRD, which was even seen in patients who were refractory to both a BTK inhibitor and venetoclax. Siddiqui concluded by noting that the phase 2 monotherapy expansion of the TRANSCEND CLL 004 study is currently enrolling.