FDA Approves Liso-Cel in Relapsed or Refractory CLL/SLL

• Lisocabtagene maraleucel (liso-cel; Breyanzi) has been approved by the FDA in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) given a prior Bruton tyrosine kinase inhibitor (BTKi) and B-cell lymphoma 2 inhibitor (BCL2i).
• This marks the first chimeric antigen receptor (CAR) T-cell therapy available for this patient population.
• Findings from the TRANSCEND CLL 004 (NCT03331198) support this regulatory decision.

The FDA approved liso-cel, expanding its current indication to include adult patients with relapsed or refractory CLL or SLL who received a prior BTKi and BCL2i.¹

This approval is supported by data from the primary analysis of the phase 1/2 TRANSCEND CLL 004 study where liso-cel led to promising responses when used as a treatment for patients with relapsed/refractory CLL/SLL.^2,3 Among the 87 patients treated with liso-cel at dose level 2, the complete response (CR) rate/CR with incomplete hematologic recovery (CRi) rate as assessed by independent review committee (IRC) at a median follow-up of 21.0 months (95% CI, 17.5-26.6) was 18% (95% CI, 11%-28%). The IRC-assessed objective response rate in this group was 47% (95% CI, 36%-58%).

Further, the rate of undetectable minimal residual disease (uMRD) in the blood was 64% (95% CI, 53%-74%), and the uMRD rate in marrow was 59% (95% CI, 48%-69%). The best overall responses consisted of CR/CRis (18%), partial responses (PR)/non-confirmed PR (29%), stable disease (39%), and progressive disease (7%).

"For this difficult-to-treat multiple refractory patient population, this 1 shot of CAR T cells seems to lead to hopefully years of remission for these patients without maintenance, without pills, without continuous infusions, which is sort of priceless for them. They enjoy their quality of life and treatment, so I think it has a lot of clinical benefits," said Tanya Siddiqui, MD, hematologist, associate professor, medical director in the Division of Lymphoma at City of Hope Orange County in Duarte, California, in an interview with Targeted Oncology^TM.

Additional findings from the study were presented at the 2023 American Society of Clinical Oncology Annual Meeting. Six patients (7%) included in the study were not evaluable. In the full study population, the median time to first response was 1.5 months (range, 0.8-17.4) and the median time to first CR/CRi was 4.4 months (range, 1.1-17.9).

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About TRANSCEND CLL 004

The open-label, multicenter TRANSCEND CLL 004 sought to evaluate liso-cel for the treatment of patients with relapsed or refractory CLL or SLL.⁴ The phase 1 dose-escalation portion of the study evaluated the safety and recommended dose of liso-cel, which was then studied in phase 2. In phase 2 of the study, experts assessed liso-cel at the recommended dose determined in the phase 1 monotherapy arm.

The primary end point in phase 2 portion was CR rate, including CRi with bone marrow recovery.

Enrollment was open to patients aged 18 years and older with relapsed/refractory CLL/SLL. Patients were required to have previously progressed on or be ineligible for BTK inhibition; be at high or standard risk, defined by absence of efficacy with at least 2 or at least 3 prior lines of treatment, respectively; have an ECOG performance status of 0 or 1; adequate bone marrow, organ, and cardiac function; and absence of Richter transformation and active central nervous system involvement by malignancy.

"I think the biggest message to send, especially to referring physicians and patients alike, is send patients or have them come for clinical trials, because without clinical trials, we cannot get new drugs approved by the FDA and onto the market for the rest of the population to use," explained Siddiqi.

REFERENCES:

1. U.S. FDA approves Bristol Myers Squibb's Breyanzi as the first and only CAR T cell therapy for adults with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). News release. Bristol Myers Squibb. March 14, 2024. Accessed March 15, 2024. https://tinyurl.com/yf8ztnr5

2. U.S. food and drug administration accepts for priority review Bristol Myers Squibb’s application for breyanzi (lisocabtagene maraleucel) for relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). News release. Bristol Myers Squibb. November 9, 2023. Accessed January 15, 2024. https://tinyurl.com/434347ka

3. 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. J Clin Oncol. 2023;41(suppl 16):7501. doi:10.1200/JCO.2023.41.16_suppl.7501

4. Study evaluating safety and efficacy of JCAR017 in subjects with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). ClinicalTrials.gov. Updated August 29, 2023. Accessed January 15, 2024. https://clinicaltrials.gov/study/NCT03331198