Lisocabtagene Maraleucel, a CD19-Directed CAR T-Cell Product, in High-Risk Patients with R/R CLL/SLL, Including Those Previously Treated with Ibrutinib

Conference Correspondent —January 16, 2020

Lisocabtagene maraleucel (liso-cel) is an investigational, anti-CD19, defined composition, 4-1BB chimeric antigen receptor (CAR) T-cell product, administered at a target dose of CD4+ and CD8+ CAR T-cells. An ongoing, open-label phase 1/2 (TRANSCEND CLL 004; NCT03331198) study is evaluating liso-cel in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL); updated results of the study were presented at the 2019 ASH meeting and are summarized here.

Eligible patients with CLL/SLL had received ≥3 (standard-risk disease) or ≥2 (high-risk disease) prior lines of therapy, including a Bruton’s tyrosine kinase inhibitor (BTKi). Following lymphodepletion (3 days) with fludarabine/cyclophosphamide, patients received liso-cel infusion (dose level [DL]1 = 50 × 106 and DL2 = 100 × 106 CAR+ T-cells). Dose-limiting toxicities (DLTs) were evaluated for 28 days postinfusion. Minimal residual disease (MRD) was assessed at a sensitivity of ≤10-4 in blood and/or bone marrow (BM) lymphocytes. Liso-cel CAR T-cells were monitored by flow cytometry of blood cells from treated patients over time. Serum cytokines and chemokines were assessed via an electrochemiluminescence platform.

In this analysis, 23 patients were evaluable for safety and 22 for efficacy. The median age among the study population was 66 years (range, 49-79); the majority (83% [19/23]) of patients had high-risk disease (del[17p], TP53 mutation, unmutated IGHV, or complex karyotype). Patients had received a median of 5 prior therapies (range, 2-11). All patients had received prior ibrutinib; 39% (9/23) had progressed on a BTKi and failed venetoclax; 91% (21/23) were R/R to ibrutinib.

Using established processes, liso-cel was successfully manufactured in 96% of patients. At DL2, 2 patients had DLTs (grade 4 hypertension in 1 patient; grade 3 encephalopathy, grade 3 muscle weakness, and grade 4 tumor lysis syndrome in 1 patient). The most common grade 3/4 treatment-emergent adverse events were thrombocytopenia (70%), anemia (78%), neutropenia (56.5%), and leukopenia (43.5%). Grade 3 cytokine release syndrome (CRS) was reported in 2 patients, and grade ≥3 neurologic events (NEs), including encephalopathy, were reported in 5 patients. The median time to first onset of CRS was 4 days (range, 1-10), and time to onset of NEs was 4 days (range, 2-21). The median duration of CRS and NEs was 12 days (range, 2-50) and 21 days (range, 6-56), respectively.

At a median follow-up of 11 months, the best overall response rate among 22 evaluable patients was 81.5%, including a complete response (CR)/CR with incomplete hematologic response rate of 45.5%. The depth of responses increased over time in 6 patients. The majority of MRD-evaluable patients (n = 20) achieved blood (15 [75%]) and/or BM (13 [65%]) undetectable (u)MRD.

The study investigators concluded that liso-cel treatment in heavily pretreated patients with R/R CLL/SLL who had failed ibrutinib was manageable and produced durable uMRD responses.

Siddiqi T, et al. ASH Abstract 503. Session 642.

Related Articles
Triplet Therapy with Acalabrutinib, Venetoclax, and Obinutuzumab in Patients with Treatment-Naïve Chronic Lymphocytic Leukemia
Conference Correspondent
Use of a time-limited triplet combination of acalabrutinib, venetoclax, and obinutuzumab in patients with chronic lymphocytic leukemia offers high rates of undetectable minimal residual disease in bone marrow with acceptable tolerability.
Resistance to Acalabrutinib in Chronic Lymphocytic Leukemia Is Mediated Predominantly by BTK Mutations
Conference Correspondent
For patients with chronic lymphocytic leukemia who are treated with acalabrutinib, disease progression is largely attributed to specific mutations in Bruton tyrosine kinase (BTK). Acalabrutinib resistance mechanisms are similar to those seen with ibrutinib.
Ibrutinib + Venetoclax for First-Line Treatment of CLL: Results from the MRD Cohort of the Phase 2 CAPTIVATE Study
Conference Correspondent
In the minimal residual disease (MRD) cohort of the phase 2 CAPTIVATE study, first-line ibrutinib + venetoclax treatment resulted in high rates of undetectable MRD in both peripheral blood and bone marrow of patients with chronic lymphocytic leukemia (CLL).
Last modified: November 5, 2020

Subscribe to the Journal of Oncology Navigation & Survivorship®

To sign up for our print publication or e-newsletter, please enter your contact information below.

  • First Name *
    Last Name *
     
     
    Profession or Role
    Primary Specialty or Disease State

    Please enter your mailing address.

    Address
     
    Address Line 2
    City
     
    State
    Zip Code
    Country