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Lisocabtagene Maraleucel for Relapsed or Refractory Large B-Cell Lymphomas


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In the TRANSCEND NHL 001 study reported in The Lancet, Jeremy S. Abramson, MD, and colleagues found that the autologous CD19-directed chimeric antigen receptor (CAR) T-cell agent lisocabtagene maraleucel (liso-cel) produced a high response rate in patients with relapsed or refractory large B-cell lymphomas.

Jeremy S. Abramson, MD

Jeremy S. Abramson, MD

Study Details

In the multicohort seamless design trial, conducted at 14 U.S. centers, 344 adult patients underwent leukapheresis for manufacture of CAR-positive T cells (liso-cel) between January 2016 and July 2019. Eligible histologic subgroups consisted of individuals with diffuse large B-cell lymphoma; high-grade B-cell lymphoma with rearrangements of MYC and either BCL2, BCL6, or both; diffuse large B-cell lymphoma transformed from any indolent lymphoma; primary mediastinal B-cell lymphoma; and follicular lymphoma grade 3B.

Patients were assigned to the sequentially tested liso-cel target dose levels of 50 × 10⁶ (one or two doses), 100 × 10⁶, and 150 × 10⁶ CAR-positive T cells; treatment was given as sequential infusion of CD8-positive and CD4-positive CAR-positive T cells at equal target doses. Patients had received a median of three (range = 1–8) previous lines of systemic treatment.

Responses

Of the 344 patients undergoing leukapheresis, 269 received at least one dose of liso-cel (safety population). Of these, 256 patients were included in the efficacy-evaluable population (all patients who had confirmed positron emission tomography–positive disease and received at least one dose of liso-cel). The overall safety and activity of liso-cel did not differ by dose level; the recommended target dose was 100 × 10⁶ CAR-positive T cells as 50 × 106 CD8-positive and 50 × 106 CD4-positive CAR-positive T cells.  

Among the 256 efficacy-evaluable patients, objective response on Lugano criteria as assessed by independent review committee was observed in 186 (73%), with complete response in 136 (53%). Median time to first complete or partial response was 1.0 month (range = 0.7–8.9 months). Median duration of response was not reached after median follow-up for response duration of 12.0 months; the estimated proportion of responders with response ongoing at 1 year was 55% among all responders and 65% among those with complete response.

KEY POINTS

  • Objective response was observed in 73% of evaluable patients, with complete response in 53%.
  • Median duration of response was not reached.

Median progression-free survival (after follow-up of 12.3 months) was 6.8 months; it was not reached among patients with complete response. Progression-free survival at 1 year was 44% for the total population and 65% among patients with complete response. Median overall survival was 21.1 months (after median follow-up of 17.5 months) and was not reached among patients with complete response; estimated 1-year rates were 58% for the total population and 86% among complete responders.

Adverse Events

The most common grade ≥ 3 adverse events were neutropenia (60%), anemia (37%), and thrombocytopenia (27%). Cytokine-release syndrome and neurological events of any grade occurred in 42% and 30% of patients and were grade ≥ 3 in 2% and 10%, respectively. Dose-limiting toxicity occurred in nine patients (6%), including one who died from diffuse alveolar damage. Febrile neutropenia occurred in 9% of patients.

Adverse events led to death in seven patients (3%), with causes consisting of diffuse alveolar damage, pulmonary hemorrhage, multiple organ dysfunction syndrome, cardiomyopathy, leukoencephalopathy, septic shock, and progressive multifocal leukoencephalopathy.

The investigators concluded, “Use of liso-cel resulted in a high objective response rate, with a low incidence of grade 3 or worse cytokine release syndrome and neurological events in patients with relapsed or refractory large B-cell lymphomas, including those with diverse histological subtypes and high-risk features. Liso-cel is under further evaluation at first relapse in large B-cell lymphomas and as a treatment for other relapsed or refractory B-cell malignancies.”

Dr. Abramson, of Massachusetts General Hospital, is the corresponding author for The Lancet article.

Disclosure: The study was funded by Juno Therapeutics, a Bristol Myers Squibb Company. For full disclosures of the study authors, visit thelancet.com.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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