Liso-cel Meets CR End Point in Relapsed/Refractory CLL/SLL

The CAR T-cell therapy lisocabtagene maraleucel (liso-cel; Breyanzi) induced complete responses (CRs) in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL), meeting the primary end point of the phase 1/2 TRANSCEND CLL 004 trial (NCT03331198).¹

The primary end point of CR rate was compared with CR rates from a historical control of patients with relapsed/refractory CLL who were refractory to a BTK inhibitor and pretreated with a BCL-2 inhibitor. Bristol Myers Squibb (BMS) expects to release detailed findings at an upcoming medical meeting.

“CLL is an incurable disease with complex biology and immune dysregulation that has made the development of T cell–based therapies that provide deep remission very challenging,” Anne Kerber, BMS senior vice president and head of Cell Therapy Development, stated in a news release. “In a population that has limited options, the TRANSCEND CLL 004 study represents the first multicenter trial evaluating a CAR T-cell therapy in heavily pretreated patients with relapsed or refractory CLL or SLL, with results showing the potential of [liso-cel] as a personalized one-time treatment approach for patients with this difficult-to-treat disease.”

The open-label, single-arm, multicenter, phase 1/2 TRANSCEND CLL 004 trial is evaluating liso-cel as monotherapy and in combination with ibrutinib (Imbruvica) or venetoclax (Venclexta) in patients with relapsed/refractory CLL or SLL.² Patients enrolled to receive liso-cel monotherapy are required to have failed or be ineligible for treatment with a BTK inhibitor. Patients with high-risk features must have failed at least 2 prior lines of therapy, and those with standard-risk features must have failed at least 3 prior lines of therapy. Other key inclusion criteria include an ECOG performance status of 0 or 1 and adequate bone marrow and organ function.

For patients who received prior CD19-targeted therapy, they must have confirmed CD19-positive disease following the completion of prior treatment.

Key exclusion criteria include known active central nervous system metastases and a history of another primary malignancy that has not been in remission for at least 2 years. Patients with Richter’s transformation or prior treatment with any gene therapy were not eligible.

In phase 1 of the trial, patients received escalating doses of liso-cel to assess safety and establish the recommended phase 2 dose (RP2D). Patients enrolled in the phase 2 expansion cohort are receiving liso-cel at the RP2D of 100 × 10⁶ CAR+ T cells.³

The primary end point in phase 2 consists of CR rate, including complete remission with incomplete bone marrow recovery, by independent review committee assessment per the International Workshop on Chronic Lymphocytic Leukemia 2018 guidelines.

No new safety signals were reported for liso-cel.Previously reported data from the phase 1 portion of the trial showed that liso-cel was well tolerated and elicited rapid and deep responses in patients with relapsed/refractory CLL/SLL.³

Among 22 patients evaluable for efficacy, liso-cel demonstrated an overall response rate or 82%, including a CR rate of 45%. Additionally, among 20 patients evaluable for minimal residual disease (MRD), 75% and 65% achieved undetectable MRD in the blood and bone marrow, respectively.

Regarding safety, 74% of patients experienced cytokine release syndrome (CRS), and the rate of grade 3 CRS was 9%. Furthermore, 39% experienced any-grade neurological adverse effects, including 22% of patients with grade 3/4 neurological events.

References

1. Bristol Myers Squibb announces TRANSCEND CLL 004 trial of Breyanzi® (lisocabtagene maraleucel) met primary endpoint of complete response rate in patients with relapsed or refractory chronic lymphocytic leukemia. News release. Bristol Myers Squibb. January 26, 2023. Accessed January 26, 2023. http://bit.ly/3XJmqHE
2. 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 November 25, 2022. Accessed January 26, 2023. https://clinicaltrials.gov/ct2/show/NCT03331198
3. Siddiqi T, Soumerai JD, Dorritie KA, et al. Phase 1 TRANSCEND CLL 004 study of lisocabtagene maraleucel in patients with relapsed/refractory CLL or SLL. Blood. 2022;139(12):1794-1806. doi:10.1182/blood.2021011895