Liso-cel Sustains Disease Improvement in Primary Refractory or Early Relapsed LBCL

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Patients with large B-cell lymphoma in the TRANSFORM trial showed improvements over 3-year period compared with standard of care.

Manali K. Kamdar, MD, a hematologist/oncologist and the clinical director of Lymphoma Services at the University of Colorado Cancer Center

Manali K. Kamdar, MD

(Credit: University of Colorado)

The use of lisocabtagene maraleucel (Breyanzi; Bristol Myers Squibb) as a second-line therapy in patients with primary refractory or early relapsed large B-cell lymphoma (LBCL) appears to be safe and was associated with an accumulating therapeutic response and improvement in efficacy end points compared with standard of care treatment, according to long-term data with a median follow-up of approximately 3 years.1

The investigators noted that the data on the autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy, known colloquially as liso-cel, confirm the ongoing benefit of its use. The data were compiled from an analysis of the phase 3 TRANSFORM clinical trial (NCT03575351) and were presented by Manali K. Kamdar, MD, a hematologist/oncologist and the clinical director of Lymphoma Services at the University of Colorado Cancer Center, at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, held May 31 to June 4, in Chicago, Illinois.

In an interview after her presentation, Kamdar told CGTLive® that "the FDA approved liso-cel as a second-line option for patients with primary refractory and early relapsed large B cell lymphoma if they're transplant–eligible based on the TRANSFORM study. So I think this 3 year update is important to figure out if all of these analyses hold true. The short answer is yes they do." She added that these 3-year data "demonstrate superior efficacy, safety, extremely [good] tolerability, and thus [do] support its use in transplant–eligible primary refractory and early relapsing large B cell lymphoma patients who are transplant eligible because it does support a curative potential for these patients."

Recent Regulatory Decisions for Liso-Cel

The CAR T therapy has emerged as an effective option for many patient populations in recent years. In fact, this presentation at ASCO comes just days after the CAR T therapy received FDA approval for the treatment of relapsed/refractory mantle cell lymphoma (MCL) in those who had been previously treated with at least 2 lines of systemic therapy, including a Bruton tyrosine kinase inhibitor—the fourth subtype of non-Hodgkin lymphoma the treatment has received agency approval.2 That decision was based on data from the MCL cohort in the phase 1 TRANSCEND NHL 001 clinical trial (NCT02631044). And, just 15 days prior to that, the treatment was awarded accelerated approval for adults with relapsed or refractory follicular lymphoma (FL) who have received 2 or more prior lines of systemic therapy.3

READ MORE: No GvHD With Allogeneic CRISPR-edited CAR T for LBCL, PFS Associated With Partial HLA Match

Liso-cel received its FDA approval for adults with LBCL in 2022,4 and in 2023,5 the treatment was also approved by the European Commission for the treatment of adult patients with diffuse LBCL, as well as high-grade B-cell lymphoma (HGBCL), primary mediastinal LBCL (PMBCL), and FL grade 3B whose disease relapsed within 12 months from the completion of first-line chemoimmunotherapy or those whose disease is refractory to first-line chemoimmunotherapy.

ASCO 2024 Analysis

Kamdar and colleagues noted that previously, “in prespecified interim and primary analyses of TRANSFORM, liso-cel showed significant improvements in efficacy vs standard of care in patients with relapsed/refractory LBCL.”

For this analysis, 184 patients were randomly assigned (n = 92 per arm) to either standard of care of treatment, of which 66% (n = 61) crossed over to receive liso-cel in the open-label phase. The median follow-up was 33.9 months (range, 0.9-53.0), and the median event-free survival (EFS), progression-free survival (PFS), and duration of response (DOR) were longer for liso-cel vs standard of care, similar to the primary analysis. All told, EFS and PFS values for liso-cel vs standard of care were 45.8 (95% CI, 35.2-56.5) vs 19.1 (95% CI, 11.0-27.3), 50.9 (95% CI, 39.9-62.0) vs 26.5 (95% CI, 15.9-37.1) at 36 months, respectively. Media DOR was not reached (95% CI, 16.9 to not reached) for the liso-cel arm compared with 9.1 months (95% CI, 5.1 to not reached) with standard of care.

Additionally, of the 76 total deaths (liso-cel, n = 34; standard of care, n = 42; crossover pts, n = 33), 10 occurred since the start of the primary analysis (liso-cel, n = 6; SOC, n = 4; all crossover pts), and the majority (n = 6) were because of disease progression or complications.

As for safety, Rates of any-grade and severe cytokine release syndrome (CRS) and neurological events were low (1% and 4% grade 3 events, respectively), with no grade 4 or 5 events, and patients required little use of tocilizumab and steroids to manage those adverse events, without prophylactic use.

Kamdar and colleagues wrote that the “safety results were consistent with the primary analysis.” The primary analysis showed that 48.9% of patients treated with liso-cel experienced CRS, with 1% experiencing grade 3 cases of CRS; and 10.9% of patients treated with liso-cel experienced neurologic events, with 4.3% experiencing grade 3 cases.

Altogether, in the phase 3 study, patients in the liso-cel arm underwent lymphodepletion followed by liso-cel (100 × 106 CAR+ T cells), with bridging therapy allowed. Standard of care patients received 3 cycles of chemotherapy; those who responded then proceeded to high-dose chemotherapy plus autologous stem cell transplantation. Crossover to receive liso-cel was allowed for standard-of-care patients if criteria were met.

Expert Perspectives on Liso-Cel

In a recent News Network program put on by CGTLive’s sister publication, OncLive, experts Caron A. Jacobson, MD, and Miguel-Angel Perales, MD, discussed liso-cel while reviewing the impact of real-world analysis and how they may shape guidelines and clinical approaches with respect to the use of CAR T-cell therapy in LBCL, particularly noting how continued research bolsters the safety profile of these agents. Check out that conversation below for their insights.

Click here for more coverage from ASCO 2024.

REFERENCES
1. Kamdar MK, Solomon SR, Arnason J, et al. Lisocabtagene maraleucel (liso-cel) vs standard of care (SOC) with salvage chemotherapy (CT) followed by autologous stem cell transplantation (ASCT) as second-line (2L) treatment in patients (pt) with R/R large B-cell lymphoma (LBCL): 3-year follow-up (FU) from the randomized, phase 3 TRANSFORM study. Presented at: 2024 (ASCO) Annual Meeting; May 31 - June 4; Chicago, Illinois. Abstract #7013
2. U.S. Food and Drug Administration Approves Bristol Myers Squibb’s Breyanzi as a New CAR T Cell Therapy for Relapsed or Refractory Mantle Cell Lymphoma. News release. FDA. May 30, 2024. Accessed June 3, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-lisocabtagene-maraleucel-follicular-lymphoma
3. FDA grants accelerated approval to lisocabtagene maraleucel for follicular lymphoma. News release. FDA. May 15, 2024. Accessed June 3, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-lisocabtagene-maraleucel-follicular-lymphoma
4. Bristol Myers Squibb receives European Commission approval for CAR T cell therapy breyanzi (lisocabtagene maraleucel) for certain forms of relapsed or refractory large B-cell lymphoma. News release. Bristol Myers Squibb. April 5, 2022. Accessed June 3, 2024. https://news.bms.com/news/corporate-financial/2022/Bristol-Myers-Squibb-Receives-European-Commission-Approval-for-CAR-T-Cell-Therapy-Breyanzi-lisocabtagene-maraleucel-for-Certain-Forms-of-Relapsed-or-Refractory-Large-B-cell-Lymphoma/default.aspx
5. Bristol Myers Squibb receives European Commission approval for CAR T cell therapy Breyanzi (lisocabtagene maraleucel) for relapsed or refractory large B-cell lymphoma after one prior therapy. News release. Bristol Myers Squibb. May 3, 2023. Accessed June 3, 2024. https://news.bms.com/news/corporate-financial/2023/Bristol-Myers-Squibb-Receives-European-Commission-Approval-for-CAR-T-Cell-Therapy-Breyanzi-lisocabtagene-maraleucel-for-Relapsed-or-Refractory-Large-B-cell-Lymphoma-After-One-Prior-Therapy/default.aspx
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