Liso-cel Achieves Durable Responses in Patients With R/R Follicular Lymphoma and R/R Mantle Cell Lymphoma

Lisocabtagene maraleucel (liso-cel; Breyanzi; Bristol Myers Squibb), a CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy currently marketed in the United States and European Union for large B-cell lymphoma indications, has produced durable responses among patients with relapses/refractory (r/r) follicular lymphoma (FL) treated in the phase 2 TRANSCEND FL clinical trial (NCT04245839) and patients with r/r mantle cell lymphoma (MCL) treated in the phase 1 TRANSCEND NHL 001 clinical trial (NCT02631044).¹

In TRANSCEND FL, 101 patients with FL that was r/r after 2 prior lines of therapy were evaluated for efficacy. The overall response rate (ORR) in this group was 97% (95% CI, 91.6-99.4; one-sided P <.0001) and the complete response (CR) rate was 94% (95% CI, 87.5-97.8; one-sided P <.0001). At a median follow-up of 16.6 months, the median duration of response was not reached. Furthermore, at 12 months of follow-up, 81.9% of patients whose disease responded to the therapy had sustained responses. At a median follow-up of 17.5 months, median progression-free survival (PFS) was not reached; 80.7% of the patients achieved 12-month PFS.

The safety analysis included 130 patients with FL that was r/r after 1 or 2 prior lines of therapy. Among these patients, who had a median follow-up of 18.9 months, 58% experienced cases of cytokine release syndrome (CRS) and 15% experienced neurological events (NEs). Furthermore, 1% of patients experienced grade 3 CRS and 2% of patients experienced grade 3 NEs. There were no cases of CRS or NEs grade 4 or higher observed. The safety profile of liso-cel in this group was deemed manageable.

“In the treatment of r/r FL, there are few options that offer significant and lasting responses, particularly for patients with high-risk disease features and those who experience early disease progression after front-line therapy,” Franck Morschhauser, MD, PhD, the lead investigator and a professor of hematology at Centre Hospitalier Universitaire de Lille, Groupe de Recherche sur les forms Injectables et les Technologies Associées, in Lille, France, said in a statement.¹ “In TRANSCEND FL, the overall and complete response rates achieved with liso-cel were very high, and appear mostly durable at 12 months, and, importantly, the safety profile was favorable. This data shows the potential of liso-cel as a promising treatment option for patients with relapsed or refractory follicular lymphoma.”

In TRANSCEND NHL 001, 74 patients with MCL that was r/r after 2 or more prior lines of therapy were included in the efficacy analysis for the trial’s MCL cohort. At a median follow-up of 16.1 months, the ORR for these patients was 86.5% (95% CI, 76.5-93.3; one-sided P <.0001) and the CR rate was 74.3% (95% CI, 62.8-83.8; one-sided P <.0001). All of the patients in this group had previously been treated with a BTK inhibitor. The patients received liso-cel at 2 dose-levels: 50x10⁶ CAR-positive viable T-cells and 100x10⁶ CAR-positive viable T-cells.

The safety analysis included 88 patients. In this group, 61% of patients experienced cases of CRS and 31% of patients experienced NEs. Grade 3 to grade 4 cases of CRS were observed in 1% of the patients and grade 3 to grade 4 NEs were observed in 9% of the patients. Grade 5 cases of CRS and grade 5 NEs did not occur in any of the patients in the safety set. The safety profile of liso-cel in this group was deemed well-tolerated.

“Despite advances in treatment, there remains a critical unmet need for additional therapies that offer deep and durable responses in patients with high-risk, aggressive r/r MCL,” Michael Wang, MD, the lead investigator and a professor in the Department of Lymphoma and Myeloma in the Division of Cancer Medicine at the University of Texas MD Anderson Cancer Center in Houston, Texas, said in a statement.¹ “Liso-cel offers the potential for complete responses with a 1-time infusion and a manageable safety profile, representing a potential new treatment option for these patients.”

The new data from TRANSCEND FL and TRANSCEND NHL 001 are the latest in a series of positive updates regarding liso-cel that have been announced by Bristol Myers Squibb in recent months. In early May, the company noted that TRANSCEND FL and TRANSCEND NHL 001 had met the primary end point of ORR and that both trials also met the CR rate end point.² A few days later, it was announced that liso-cel had been approved by the European Commission in all EU member states for the treatment of adult patients with diffuse large B-cell lymphoma (LBCL), high grade B-cell lymphoma, primary mediastinal LBCL, and FL grade 3B (FL3B) whose disease relapsed within 12 months from the completion of first-line chemoimmunotherapy or those whose disease is refractory to first-line chemoimmunotherapy.³ Then, in early June, data showing that liso-cel had produced durable CRs among patients with r/r chronic lymphocytic leukemia and small lymphocytic lymphoma treated in the phase 1/2 TRANSCEND CLL 004 clinical trial (NCT03331198) were presented at the American Society of Clinical Oncology (ASCO) 2023 Annual Meeting, held June 2 to 6, in Chicago, Illinois.^4,5

REFERENCES
1. Bristol Myers Squibb’s Breyanzi (lisocabtagene maraleucel) delivers deep and durable responses in relapsed or refractory follicular lymphoma and mantle cell lymphoma in TRANSCEND clinical trials presented at ICML 2023. News release. Bristol Myers Squibb. June 17, 2023. Accessed June 23, 2023. https://news.bms.com/news/details/2023/Bristol-Myers-Squibbs-Breyanzi-lisocabtagene-maraleucel-Delivers-Deep-and-Durable-Responses-in-Relapsed-or-Refractory-Follicular-Lymphoma-and-Mantle-Cell-Lymphoma-in-TRANSCEND-Clinical-Trials-Presented-at-ICML-2023/default.aspx
2. Bristol Myers Squibb’s TRANSCEND FL and TRANSCEND NHL 001 studies of Breyanzi (lisocabtagene maraleucel) in relapsed or refractory follicular lymphoma and mantle cell lymphoma meet primary endpoint of overall response rate. News release. Bristol Myers Squibb. May 1, 2023. Accessed June 23, 2023. https://news.bms.com/news/corporate-financial/2023/Bristol-Myers-Squibbs-TRANSCEND-FL-and-TRANSCEND-NHL-001-Studies-of-Breyanzi-lisocabtagene-maraleucelin-Relapsed-or-Refractory-Follicular-Lymphoma-and-Mantle-Cell-Lymphoma-Meet-Primary-Endpoint-of-Overall-Response-Rate/default.aspx
3. 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 23, 2023. 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
4. Siddiqi T, Maloney DG, Kenderian S, et al. Lisocabtagene maraleucel (liso-cel) in R/R chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL): Primary analysis of TRANSCEND CLL 004. Presented at: the American Society of Clinical Oncology (ASCO) 2023 Annual Meeting, held June 2-6, in Chicago, Illinois. Abstract #7501
5. Bristol Myers Squibb’s Breyanzi (lisocabtagene maraleucel) is first and only CAR T to deliver deep and durable efficacy in pivotal multicenter trial in relapsed or refractory chronic lymphocytic leukemia, based on data presented at ASCO 2023. News release. Bristol Myers Squibb. May 25, 2023. Accessed June 23, 2023. https://news.bms.com/news/corporate-financial/2023/Bristol-Myers-Squibbs-Breyanzi-lisocabtagene-maraleucel-is-First-and-Only-CAR-T-to-Deliver-Deep-and-Durable-Efficacy-in-Pivotal-Multicenter-Trial-in-Relapsed-or-Refractory-Chronic-Lymphocytic-Leukemia-Based-on-Data-Presented-at-ASCO-2023/default.aspx