New Data Supports Breyanzi’s Expansion to Chronic Lymphocytic Leukemia

Breyanzi is currently approved for the second-line or later treatment of large B-cell lymphomas.

The phase 1/2 TRANSCEND CLL 004 trial (NCT03331198) of lisocabtagene maraleucel (Breyanzi; Bristol Myers Squibb) met its primary endpoint of achieving complete responses (CRs) compared to historical control in the prespecified subset of patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) refractory to a BTK inhibitor and pretreated with a BCL-2 inhibitor, according to topline results from the study announced today.1

“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, senior vice president and head, Cell Therapy Development, Bristol Myers Squibb (BMS), said in a statement.1 “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 pre-treated patients with relapsed or refractory CLL or SLL, with results showing the potential of Breyanzi as a personalized one-time treatment approach for patients with this difficult-to-treat disease.”

The multicenter, open-label, single-arm TRANSCEND CLL 004 study is evaluating Breyanzi, a CD19-targted chimeric antigen receptor (CAR) T-cell therapy, in patients with R/R CLL or small lymphocytic lymphoma. The trial started off with a phase 1 portion which evaluated safety and determined the phase 2 recommended dose while the phase 2 portion is currently evaluating efficacy of this dose. The phase 2 portion met its primary endpoint of CR rate including CR with incomplete bone marrow recovery, based on independent review committee according to the International Workshop on Chronic Lymphocytic Leukemia 2018 guidelines. More detailed data from TRANSCENNE CLL 004 will be presented at an upcoming medical meeting and BMS will discuss these results with regulatory agencies.

Breyanzi was approved by the FDA as a second-line therapy for patients with large B-cell lymphomas (LBCL) that relapsed or were refractory within 12 months of first-line treatment who are not eligible for hematopoietic stem cell transplant in June 2022.The therapy was original approved in February 2021 for adults with relapsed or refractory diffuse LBCL who have not responded to at least 2 other treatments based off data from the pivotal phase 3 TRANSFORM (NCT03575351) trial.2,3 It is also approved in Europe, Switzerland, Canada and Japan for R/R LBCL 2 or more lines of systemic therapy and is currently being evaluated in earlier lines of treatment of LBCL and other types of lymphoma and leukemias.

READ MORE: Advocating for Patients With Chronic Lymphocytic Leukemia

BMS also recently announced results from the phase 3 TRANSFORM study (NCT03575351) that demonstrated superiority over standard-of-care (SOC) chemotherapy induction and autologous stem cell transplant (ASCT) in second-line treatment of high-risk, R/R LBCL. Second-line liso-cel was found to reduce the risk of an event occurring by 64.4% compared with SOC chemoimmunotherapy induction and ASCT.4 The median event-free survival (EFS) was not yet reached with liso-cel compared with 2.4 months for SOC (HR, 0.356; 95% CI, 0.243-0.522) after a median follow-up of 17.5 months in the open-label study. The 18-month EFS rate was 52.6% with liso-cel (95% CI, 42.3%-62.9%) vs 20.8% with SOC (95% CI, 12.2%-29.5%).

“The primary analysis of the TRANSFORM study confirms the superiority of liso-cel over SOC. Liso-cel resulted in significant improvements in event-free survival, complete response rates, and progression-free survival, with 18-month event-free and progression-free survival rates for liso-cel more than double those of standard of care,” lead study author Jeremy S. Abramson, MD, from the Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, said in a statement.4 “Despite allowing for crossover, overall survival numerically favored liso-cel and a supportive overall survival adjusting for crossover showed an overall survival benefit in favor of liso-cel."

1. Bristol Myers Squibb announces TRANSCEND CLL 004 trial of Breyanzi® (lisocabtagenemaraleucel) met primary endpoint of complete response rate in patients with relapsed or refractory chronic lymphocytic leukemia. News release. Bristol Myers Squibb. January 25, 2023.
2. U.S. FDA Approves Bristol Myers Squibb’s CAR T Cell Therapy Breyanzi® for Relapsed or Refractory Large B-cell Lymphoma After One Prior Therapy. News release. Bristol Myers Squibb. June 24, 2022.
3. FDA Approves New Treatment For Adults With Relapsed Or Refractory Large-B-Cell Lymphoma. News release. FDA. February 5, 2021.
4. Abramson JS, Solomon SR, Arnason JE, et al. Lisocabtagenemaraleucel (liso-cel) versus standard of care (soc) with salvage chemotherapy followed by autologous stem cell transplantation (asct) as second-line (2L) treatment in patients with relapsed or refractory large B-cell lymphoma (LBCL): primary analysis of the randomized, phase 3 Transform study. Blood. 2022;140(suppl 1):1581-1583. doi:10.1182/blood-2022-159702
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