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LISOCABTAGENE MARALEUCEL (LISO-CEL) IN R/R CHRONIC LYMPHOCYTIC LEUKEMIA (CLL)/SMALL LYMPHOCYTIC LYMPHOMA (SLL): PRIMARY ANALYSIS OF TRANSCEND CLL 004 B Introduction: b Achieving durable CR with current treatment is uncommon in patients (pts) with R/R CLL/SLL that progressed on BTKi and failed venetoclax (ven)-based treatment. Keyword: cellular therapies B Conflicts of interests pertinent to the abstract b B T. Siddiqi b Consultant or advisory role: Astra Zeneca, BMS, Celgene, Kite pharma, Beigene, Abbvie Research funding: Astra Zeneca, BMS, Celgene, Oncternal, Ascentage pharma, Kite pharma, TG therapeutics, Pharmacyclics, Juno therapeutics Other remuneration: Speaker's Bureau: Astra Zeneca, BMS, Beigene B D. G. Maloney b Consultant or advisory role: A2 Biotherapeutics, Member of the Scientific Advisory Board GRAPH Navan Technologies, Member of the Scientific Advisory Board GRAPH Chimeric Therapeutics, Member of the Scientific Advisory Board GRAPH Genentech, Member and Chair of the Lymphoma Steering Committee GRAPH BMS, Member of the JCAR017 EAP-001 Safety Review Committee GRAPH BMS, Member, CLL Strategic Council GRAPH ImmPACT Bio, Member, Clinical Advisory Board, CD19/CD20 bi-specific CAR-T Cell Therapy Program GRAPH Gilead Sciences, Member, Scientific Review Committee, Research Scholars Program in Hematologic Malignancies GRAPH Interius. [Extracted from the article]

Background: Ibrutinib has been approved by the Food and Drug Administration for the treatment of patients with untreated chronic lymphocytic leukemia (CLL) since 2016 but has not been compared with chemoimmunotherapy. We conducted a phase 3 trial to evaluate the efficacy of ibrutinib, either alone or in combination with rituximab, relative to chemoimmunotherapy.Methods: Patients 65 years of age or older who had untreated CLL were randomly assigned to receive bendamustine plus rituximab, ibrutinib, or ibrutinib plus rituximab. The primary end point was progression-free survival. The Alliance Data and Safety Monitoring Board made the decision to release the data after the protocol-specified efficacy threshold had been met.Results: A total of 183 patients were assigned to receive bendamustine plus rituximab, 182 to receive ibrutinib, and 182 to receive ibrutinib plus rituximab. Median progression-free survival was reached only with bendamustine plus rituximab. The estimated percentage of patients with progression-free survival at 2 years was 74% with bendamustine plus rituximab and was higher with ibrutinib alone (87%; hazard ratio for disease progression or death, 0.39; 95% confidence interval [CI], 0.26 to 0.58; P<0.001) and with ibrutinib plus rituximab (88%; hazard ratio, 0.38; 95% CI, 0.25 to 0.59; P<0.001). There was no significant difference between the ibrutinib-plus-rituximab group and the ibrutinib group with regard to progression-free survival (hazard ratio, 1.00; 95% CI, 0.62 to 1.62; P=0.49). With a median follow-up of 38 months, there was no significant difference among the three treatment groups with regard to overall survival. The rate of grade 3, 4, or 5 hematologic adverse events was higher with bendamustine plus rituximab (61%) than with ibrutinib or ibrutinib plus rituximab (41% and 39%, respectively), whereas the rate of grade 3, 4, or 5 nonhematologic adverse events was lower with bendamustine plus rituximab (63%) than with the ibrutinib-containing regimens (74% with each regimen).Conclusions: Among older patients with untreated CLL, treatment with ibrutinib was superior to treatment with bendamustine plus rituximab with regard to progression-free survival. There was no significant difference between ibrutinib and ibrutinib plus rituximab with regard to progression-free survival. (Funded by the National Cancer Institute and Pharmacyclics; ClinicalTrials.gov number, NCT01886872 .). [ABSTRACT FROM AUTHOR]

Background: Ibrutinib, idelalisib, and venetoclax are approved for treating CLL patients in the United States. However, there is no guidance as to their optimal sequence. Patients and methods: We conducted a multicenter, retrospective analysis of CLL patients treated with kinase inhibitors (KIs) or venetoclax. We examined demographics, discontinuation reasons, overall response rates (ORR), survival, and post-KI salvage strategies. Primary endpoint was progression-free survival (PFS). Results: A total of 683 patients were identified. Baseline characteristics were similar in the ibrutinib and idelalisib groups. ORR to ibrutinib and idelalisib as first KI was 69% and 81%, respectively. With a median follow-up of 17 months (range 1-60), median PFS and OS for the entire cohort were 35 months and not reached. Patients treated with ibrutinib (versus idelalisib) as first KI had a significantly better PFS in all settings; front-line [hazard ratios (HR) 2.8, CI 1.3-6.3, P = 0.01], relapsed-refractory (HR 2.8, CI 1.9-4.1, P < 0.001), del17p (HR 2.0, CI 1.2-3.4, P = 0.008), and complex karyotype (HR 2.5, CI 1.2-5.2, P = 0.02). At the time of initial KI failure, use of an alternate KI or venetoclax had a superior PFS when compared with chemoimmunotherapy. Furthermore, patients who discontinued ibrutinib due to progression or toxicity had marginally improved outcomes if they received venetoclax (ORR 79%) versus idelalisib (ORR 46%) (PFS HR .6, CI.3-1.0, P = 0.06). Conclusions: In the largest real-world experience of novel agents in CLL, ibrutinib appears superior to idelalisib as first KI. Furthermore, in the setting of KI failure, alternate KI or venetoclax therapy appear superior to chemoimmunotherapy combinations. The use of venetoclax upon ibrutinib failure might be superior to idelalisib. These data support the need for trials testing sequencing strategies to optimize treatment algorithms. [ABSTRACT FROM AUTHOR]