Real-world data show liso-cel drives high responses in relapsed/refractory CLL, with an 85% ORR, a 44% CR rate, and manageable safety.
Data from an analysis presented during the
The overall response rate (ORR) reported in evaluable patients (n = 41) was 85% (n = 35), which included a complete response (CR) rate of 44% (n = 18), an unconfirmed CR rate of 5% (n = 2), and a CR with incomplete blood count recovery rate of 7% (n = 3). The median time to best response was 30 days. At a median follow-up of 3.3 months, the 6-month progression-free survival rate was 92% (95% CI, 83%-100%); 1 patient relapsed. The 6-month overall survival rate in those with a CR was 88% (95% CI, 74%-100%) vs 100% (95% CI, 100%-100%) in those without a CR. Three of the 41 patients died.
Given the results of the TRANSCEND CLL 004 trial (NCT03331198), investigators wanted to evaluate the relationship between pirtobrutinib (Jaypirca) as the last line of therapy and achievement of CR. Sixty-five percent of those who received pirtobrutinib as their last line of therapy (n = 24) experienced a CR vs 35% of those who received another treatment strategy (n = 17; P = .3). The P value between pirtobrutinib exposure and response rate was not determined as statistically significant.
Some patients were also treated with other Bruton tyrosine kinase (BTK) inhibitors besides pirtobrutinib. As such, investigators evaluated the association between any exposure to BTK inhibition and efficacy. Of those who received any BTK inhibitor as their last line of therapy (n = 31), 83% achieved a CR, compared with 17% among those who did not receive a BTK inhibitor (n = 10); this association was also not statistically significant (P = .4).
“The real-world CR [rate] and ORR of liso-cel for patients with relapsed or refractory CLL is 56% and 85%, respectively,” Jennifer Huang, MD, PhD, said in a presentation of the data. “This response rate is better than that of liso-cel monotherapy as described in TRANSCEND, and efficacy is perhaps more consistent with the TRANSCEND ibrutinib [Imbruvica] cohort. This may be due to the high utilization of BTK inhibitors, including pirtobrutinib as bridging therapy.”
Huang is a physician and assistant professor in the Clinical Research Division at Fred Hutch Cancer Center in Seattle, WA, as well as an assistant professor in the Division of Hematology and Oncology at the University of Washington School of Medicine.
In March 2024, the
The real-world safety and efficacy of the CAR T-cell therapy in this population is largely unknown, she added.1 To this end, the multi-institutional, retrospective CARE CAR-T CLL study was launched.
The study included patients who received commercial liso-cel for CLL/SLL across 19 US clinical sites; patients with Richter transformation were excluded from analysis. Responses were evaluated leveraging International Workshop on Chronic Lymphocytic Leukemia criteria, and the American Society for Transplantation and Cellular Therapy criteria were used to grade cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS).
Of the 41 patients, the median age was 68 years (range, 62-72). Most patients were male (71%), White (85%), and not Hispanic or Latino (95%). The median Cumulative Illness Rating Scale score was 4 (Q1, Q3: 2, 7). Patients had an ECOG performance status of 0 (27%), 1 (59%), 2 (10%), and 3 (5%).
Moreover, 9% of patients had an intermediate CLL International Prognostic Index (IPI) score, whereas 41% had a high score and 50% had a very high score; this score was unknown for 9% of patients. Most patients had bulky disease measuring less than 5 cm (80%). The majority of patients had high-risk cytogenetics, including deletion 17p (del[17p]) or TP53 mutations (63%); a little more than one-third (39%) had complex karyotypes.
Regarding treatment history, 76% of patients had prior chemotherapy, with a median of 1 line. The median number of any prior lines of treatment was 6 (Q1, Q3: 4, 7). Most patients (95%) had received 3 or more prior lines of any treatment; 73% had received 5 or more. Treatment history included BTK inhibition for all patients, BCL-2 inhibition for 95%, and pirtobrutinib for 90%.
Most (98%) patients received bridging therapy, with stop times before leukapheresis (2%), between leukapheresis and lymphodepletion (68%), or continued post liso-cel (29%). Last lines of therapy before receipt of CAR T-cell therapy included the following:
Lastly, of those who received BTK inhibition as their last line of therapy, 59% received pirtobrutinib, and 76% received any BTK inhibitor.
Responses were evaluated across patient and disease characteristics, with the following ORs:
Responses were also assessed with regard to treatment history, with the following ORs:
“CR correlates with less bulky disease and use of bridging therapy that extends past liso-cel infusion,” Huang said.
“[We] observed an expected and tolerable safety profile,” Huang noted.
Regarding CRS, 46% of patients experienced a grade 1 event (n = 19), 29% a grade 2 event (n = 12), and 10% a grade 3 event (n = 4). With regard to ICANS, 7% of patients had a grade 1 event (n = 3), 12% had a grade 2 event (n = 5), and 12% had a grade 3 event (n = 5). No grade 4 or 5 CRS or ICANS events occurred.
Huang noted that 3 patients experienced immune effector cell–associated HLH-like syndrome; 2 of these cases were grade 2, and 1 case was grade 5.
Disclosures: Huang reported receipt of honoraria from Eisai, Inc, receipt of research funds to the institution from Bristol Myers Squibb, and serving in a consultancy role for AbbVie.
