Liso-Cel Shows Durable Responses in R/R Mantle Cell Lymphoma

"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 relapsed or refractory [MCL]," according to Michael Wang, MD, professor in the Department of Lymphoma and Myeloma and Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center.

Lisocabtagene maraleucel (liso-cel; Breyanzi) yielded long-lasting responses among patients with relapsed or refractory mantle cell lymphoma (MCL) in the phase 1 TRANSCEND NHL 001 trial (NCT02631044) and in those with follicular lymphoma in the phase 2 TRANSCEND FL trial (NCT04245839), according to a press release from Bristol Myers Squibb on the trials’ primary analysis data.

Liso-cel produced an overall response rate (ORR) of 86.5% (95% CI, 76.5%-93.3%; P <.0001) among 74 evaluable patients in the TRANSCEND NHL 001 trial after a median follow-up of 16.1 months. Additionally, the complete response (CR) rate was 74.3% (95% CI, 62.8%-83.8%; P <.0001).

“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 relapsed or refractory [MCL],” lead study investigator Michael Wang, MD, professor in the Department of Lymphoma and Myeloma and Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, said in the press release on the TRANSCEND NHL 001 data. “Liso-cel offers the potential for [CRs] with a one-time infusion and a manageable safety profile, representing a potential new treatment option for these patients.”

In the TRANSCEND FL study, the ORR was 97% (95% CI, 91.6%-99.4%; P <.0001), and the CR rate was 94% (95% CI, 87.5%-97.8%; P <.0001). With a median follow-up of 16.6 months, the median duration of response (DOR) was not reached, and 81.9% of responders had an ongoing response at 12 months. Additionally, the median progression-free survival (PFS) was not reached after a median follow-up of 17.5 months, and the 12-month PFS rate was 80.7%.

“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,” lead study investigator Franck Morschhauser, MD, PhD, professor of Hematology at Centre Hospitalier Universitaire de Lille, Groupe de Recherche sur les forms Injectables et les Technologies Associées, Lille, France, said in the press release. “[These] data show the potential of liso-cel as a promising treatment option for patients with relapsed or refractory follicular lymphoma.”

In the open-label, multi-center phase 1 TRANSCEND NHL 001 trial, investigators assessed adult patients with relapsed or refractory MCL following at least 2 lines of therapy and those with other types of relapsed or refractory B-cell non-Hodgkin lymphoma including large B-cell lymphoma and high-grade B-cell lymphoma. Patients received 50x106 or 100x106 CAR-positive viable T cells.

The primary end points included treatment-related adverse effects (TRAEs), ORR, and dose-limiting toxicities. Secondary end points included CR rate, DOR, overall survival (OS), and health-related quality of life.

Patients 18 years and older with archived tumor biopsy tumor tissue from the last relapse and a corresponding pathology report were eligible to enroll on the TRANSCEND NHL 001 trial. Additional inclusion criteria included having an ECOG performance status of 0 or 1; adequate bone marrow, renal, hepatic, pulmonary, and cardiac function; and adequate vascular access for leukapheresis.

In the open-label, international, multi-center phase 2 TRANSCEND FL trial, patients with relapsed or refractory indolent B-cell non-Hodgkin lymphoma, including those with follicular lymphoma and marginal zone lymphoma, received 100x106 CAR-positive viable T cells.

The primary end point was ORR. Secondary end points included CR rate, DOR, PFS, OS, and AEs.

Patients 18 years and older who received at least 1 line of therapy including an anti-CD20 and alkylating agent were eligible for enrollment on the TRANSCEND FL trial. Additional eligibility criteria included having an ECOG performance status of 0 or 1, adequate organ function, and adequate vascular access for leukapheresis.

Among 88 evaluable patients in the safety set of the TRANSCEND NHL 001 trial, any-grade cytokine release syndrome (CRS) affected 61% of patients, which included grade 3/4 CRS in 1% of patients. Additionally, 31% of patients had any-grade neurologic events, and 9% of patients experienced grade 3/4 instances. There were no grade 5 neurologic events or instances of CRS.

In a safety set including 130 patients in the TRANSCEND FL trial, 58% of patients experienced any-grade CRS, and 1% had grade 3 CRS. Additionally, any-grade neurologic events occurred in 15% of patients, including grade 3 events in 2% of patients. Investigators observed no instances of grade 5 CRS or neurologic events.

Investigators presented data from these trials at the 2023 International Conference on Malignant Lymphoma on June 17.

Reference

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 20, 2023. bit.ly/43RTjoC