Liso-Cel Proves Active Across High-Risk MCL Subgroups

News
Article

Liso-cel may be an effective treatment option for patients with relapsed/refractory mantle cell lymphoma and high-risk features.

M. Lia Palomba, MD

M. Lia Palomba, MD

Efficacy with lisocabtagene maraleucel (liso-cel; Breyanzi) was not hindered by the presence of a high Ki-67 proliferation index, TP53 mutations, blastoid morphology, or secondary central nervous system (CNS) lymphoma in patients with relapsed/refractory mantle cell lymphoma (MCL), according to findings from a subgroup analysis of the phase 1 TRANSCEND NHL 001 trial (NCT02631044) presented at the 2024 Tandem Meetings on Transplantation & Cellular Therapy.1

Response rates, progression-free survival (PFS), and overall survival (OS) across subgroups were consistent with the overall MCL cohort. PFS was 15.3 months (95% CI, 6.6-24.9) in the overall MCL cohort, and 15.3 months (95% CI, 6.6-24.9) in patients with Ki-67 ≥ 30%, 24.0 months (95% CI, 2.4-NR) in patients with Ki-67 < 30, 7.4 months (95% CI, 3.3-NR) for patients with a TP53 mutation, and 7.8 months (95% CI, 3.1-NR) for patients with blastoid morphology. OS rates in each of the subgroups were 18.2 months (95% CI, 12.9-36.3), 18.2 months (95% CI, 10.7-NR), 13.5 months (95% CI, 2.4-NR), 17.1 months (95% CI, 6.6-NR), and 12.9 months (95% CI, 5.6-NR), respectively.2

Notably, high overall response rates (ORR) and a sustained complete response (CR) rate was observed, as well as extended PFS and OS rates. The ORR in the overall MCL cohort was 83% (95% CI, 73.3%-90.5%). ORRs were 85% (95% CI, 74.2%-93.1%), 71% (95% CI, 41.9%-91.6%), 89% (95% CI, 66.9%-98.7%), and 70% (95% CI, 49.8%-86.2%) in the Ki-67 ≥ 30%, Ki-67 < 30, TP53 mutation, and blastoid morphology subgroups, respectively.1

While TP53 mutation assessment was limited, the study authors noted, patients in this subgroup experienced a lower median duration of response (DOR) at 6.2 months (95% CI, 2.3-NR), compared with the overall MCL cohort at 15.7 months (95% CI, 6.2-24.0). They added that this is likely due to a higher proportion of objective responders achieving a partial response (PR) rather than a CR.

Among those with a TP53 mutation who achieved a CR, responses were durable with 6 of 11 patients maintaining an ongoing response at the time of the data cutoff. Of the 7 pts with secondary CNS lymphoma, response rates were high, with an ORR of 86% (n = 6) and a CR rate of 71% (n = 5). Three of 5 patients who achieved a CR were in an ongoing response at data cutoff.

“In this analysis of patients with relapsed or refractory mantle cell lymphoma with high-risk disease features consisting of Ki-67 proliferation index of equal or more than 30%, TP53 mutations, or blastoid morphology, and patients with secondary CNS lymphoma, liso-cel demonstrated clinically meaningful efficacy across all the subgroups with high response rates and durable responses,” explained M. Lia Palomba, MD, attending physician from Memorial Sloan Kettering Cancer Center, in a presentation of the data.

High-risk features in relapsed/refractory MCL–such as TP53 mutation, high Ki-67 proliferation index, blastoid morphology, and secondary CNS involvement–are associated with a poor prognosis. Liso-cel is a CAR T-cell therapy that has been shown to be effective in relapsed/refractory MCL treatment.

A clinical trial sought to evaluate the efficacy of liso-cel in 88 patients with relapsed/refractory MCL and high-risk features after they received at least 2 prior lines of therapy. Enrollment in this cohort of the study was open to patients with PET-positive relapsed/refractory MCL after ≥ 2 lines of prior therapy, including a BTK inhibitor, alkylating agent, and CD20-targeted agent.

Once enrolled, patients were treated with liso-cel at a target dose of 50 × 106 or 100 × 106 CAR+ T cells after lymphodepleting chemotherapy. Patients were allowed to have bridging therapy.

The primary end points of the study included treatment-emergent adverse events (TEAEs) and ORR by independent review committee. Secondary end points of the study consisted of CR rate, DOR, PFS, cellular kinetics, health-related quality-of-life, hospital resource utilization, and OS.

Eighty-eight patients were enrolled in the MCL cohort and given liso-cel. Patients were followed for an average of 16 months (range, 0.4-60.5). In the overall MCL cohort, patients were heavily pretreated, having received an average of 3 prior chemotherapy regimens (range, 1-11), and the median age of patients was 68.5 years (range, 36-86). Among the patients treated with liso-cel, 75% had Ki-67 ≥ 30% and 17% had Ki-67 < 30% (not reported, 8%); 23% had TP53 mutation and 39% did not (indeterminate, 5%; not reported, 34%); and 31% had blastoid morphology and 55% did not (not reported, 15%).

The majority of patients with high-risk features also had disease refractory to last therapy received and/or to a prior BTK inhibitor, and had complex karyotype. Additionally, several patients (8%) had secondary CNS lymphoma, including 5 with refractory disease, 5 with Ki-67 ≥ 30%, 1 with a TP53 mutation, and 1 with blastoid morphology.

The safety profile of liso-cel remained consistent across different patient subgroups. This mirrored that observed with overall MCL cohort. Between high-risk and non-high-risk subgroups, TEAEs of special interest–including cytokine release syndrome (CRS) and neurological events–were similar and mostly low grade. Any-grade CRS was observed in 61% of patients and was grade 3 to 4 in 1%, while any-grade neurological events were seen in 31% of patients and were grade 3 to 4 in 9%. No grade 5 CRS or neurological events were observed.

Among the 7 pts with secondary CNS lymphoma, 5 had low-grade CRS and 3 had low-grade neurological events. No cases of grade ≥ 3 CRS or neurological events were observed; however, 1 patient had a grade ≥ 3 infection.

“Safety outcomes in the subgroups were generally consistent with those of the overall study population. There were no clear differences in pharmacokinetics observed across the subgroups,” said Palomba. “After liso-cel infusion, the incidence of B-cell aplasia peaked by month 2 in the overall study population.”

Overall, these results suggest that liso-cel is effective and safe in the MCL setting, even in patients with high-risk features. The study authors noted that more research is needed to confirm these findings, but liso-cel has the potential to improve the outlook for patients with relapsed/refractory MCL and high-risk features.

“While some subgroups were limited by small numbers, these results suggest a favorable benefit-risk profile for liso-cel in patients with high-risk disease features, a patient population for which effective treatment options are at this point very limited,” concluded Palomba.

References

  1. Palomba ML, Siddiqi T, Gordon LI, et al. Lisocabtagene maraleucel (liso-cel) in patients (Pt) with R/R MCL: subgroup analyses in pts with high-risk disease features from the MCL cohort of the TRANSCEND NHL 001. Presented at: 2024 Transplantation and Cellular Therapies Meeting; February 21-24, 2024; San Antonio, TX. Abstract 17.
  2. Wang M, Siddiqi T, Gordon LI, et al. Lisocabtagene maraleucel in relapsed/refractory mantle cell lymphoma: primary analysis of the mantle cell lymphoma cohort from TRANSCEND NHL 001, a phase I multicenter seamless design study. J Clin Oncol. Published online December 10, 2023. doi:10.1200/JCO.23.02214

Clinicians referring a patient to MSK can do so by visiting msk.org/refer, emailing referapatient@mskcc.org, or by calling 833-315-2722.

Related Videos
Sumanta Kumar Pal, MD, FASCO,
A panel of 3 experts on breast cancer
A panel of 3 experts on breast cancer
Stephen V. Liu, MD
S. Vincent Rajkumar, MD
Jonathan E. Rosenberg, MD
Jean L. Koff, MD, MS
Angela Jia, MD, PhD, of University Hospitals
Robert Wang, MD, of Fox Chase Cancer Center
Alexander Kutikov, MD, FACS, of Fox Chase Cancer Center