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Expanding Approved CAR T-Cell Therapy Treatment Options for Patients With Lymphoma

Jeremy S. Abramson, MD, MMSc

Associate Professor
Department of Medicine
Harvard Medical School
Director, Center for Lymphoma
Massachusetts General Hospital
Boston, Massachusetts


Jeremy S. Abramson, MD, MMSc, has disclosed that he has received consulting fees from AbbVie, Allogene, AstraZeneca, BeiGene, Bluebird, C4 Therapeutics, Celgene, EMD Serono, Genentech, Incyte, Karyopharm, Kite, Morphosys, and Novartis.


View ClinicalThoughts from this Author

Released: March 12, 2021

Lisocabtagene maraleucel (lisocabtagene maraleucel) is a CAR T-cell therapy approved by the FDA in February 2021 for the treatment of adult patients with relapsed or refractory (R/R) large B-cell lymphoma (including diffuse large B-cell lymphoma [DLBCL] not otherwise specified [including DLBCL arising from indolent lymphoma], high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B) after 2 or more lines of systemic therapy. In this commentary, I discuss the data supporting this approval and how I plan to incorporate this recently approved agent into my clinical practice.

Lisocabtagene Maraleucel Composition
Lisocabtagene maraleucel is a CD19‑directed CAR T‑cell therapy that includes a 4‑1BB costimulation domain and is generated by separating out the patient’s CD4+ and CD8+ T‑cells, separately transducing and expanding them, and then administering them back to the patient at equal target doses, which means giving a defined CAR T‑cell product to each patient. This is the only approved CAR T-cell product with this defined composition of T-cells.

TRANSCEND‑NHL‑001
The approval of lisocabtagene maraleucel was based on the pivotal seamless design phase I TRANSCEND‑NHL‑001 study. This study included patients with large B-cell lymphomas described in the indication above and in the Table below. Of note, the eligibility criteria for this trial were distinct from previous pivotal studies of approved CAR T-cell products, such that a broader patient population was enrolled, including patients with lymphoma involvement of their central nervous system or patients with moderate medical comorbidities (including those with a left ventricular ejection fraction as low as 40% or a creatinine clearance as low as 30 mL/min), and patients who had received previous allogeneic stem cell transplant. In addition, a small number of patients who were treated on this study had a performance status of 2.

TRANSCEND‑NHL‑001 was the largest CAR T‑cell study reported to date, with 269 evaluable patients with a median age of 63 years (range: 18-86 years). Two thirds of patients were chemotherapy refractory. The ORR in this study was 73%, with 53% of patients having a CR. Responses were rapid and durable, with first responses occurring at a median of 1 month and the median duration of response not reached at the most recent follow-up. The 1‑year PFS was 44% and 1‑year OS was 58%.

Lisocabtagene maraleucel was well tolerated, with the majority of patients having no cytokine-release syndrome (CRS) or neurologic toxicities. The incidence of CRS was 42%, with only 2% of patients having grade 3/4 CRS. Neurotoxicity was seen in 30% of patients and only 10% of patients had grade 3/4 event. Correspondingly, the use of the rescue medications tocilizumab or corticosteroids occurred in 20% and 21% of patients, respectively. The median time to onset of CRS was 5 days. The late onset and low incidence of these key toxicities lent this product to evaluation in the outpatient setting; indeed, 25 patients on the TRANSCEND trial were treated in the outpatient setting.

A Closer Look at the Approval
The table below lists the approved CAR T-cell therapies as of March 2021. Lisocabtagene maraleucel is indicated for a broader range of histologies than other products approved for R/R large B-cell lymphomas due to the broader patient population in TRANSCEND‑NHL‑001. Whereas axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel are approved for DLBCL arising from follicular lymphoma, lisocabtagene maraleucel is also approved for grade 3B follicular lymphoma and DLBCL arising from other indolent histologies.

Table. FDA-Approved CD19-Targeted CAR T-Cell Therapies

Close

Integrating Lisocabtagene Maraleucel Into Clinical Practice
The TRANSCEND‑NHL‑001 trial demonstrated that lisocabtagene maraleucel is a highly effective and well-tolerated CAR T‑cell therapy for patients with many R/R large B‑cell lymphomas, including multiple histologic subtypes and patients with high‑risk features, including double-hit or triple‑hit lymphomas, secondary central nervous system involvement, and moderate medical comorbidities. I think this is an exciting addition to our treatment armamentarium for a very difficult-to-treat population, showing high efficacy and a favorable safety profile.

Your Thoughts
How will you use lisocabtagene maraleucel for your patients with R/R large B‑cell lymphomas? Answer the polling question and join the conversation by posting a comment in the discussion section.

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