Jeremy Abramson, MD, director, Jon and Jo Ann Hagler Center for Lymphoma, Massachusetts General Hospital, associate professor of medicine, Harvard Medical School, discusses the efficacy data of second-line lisocabtagene maraleucel (liso-cel; Breyanzi) vs standard-of-care (SOC) salvage chemotherapy followed by autologous stem cell transplant from the phase 3 TRANSFORM trial (NCT03575351) done in patients with relapsed/refractory large B-cell lymphoma (LBCL).

A preliminary analysis of the trial was presented at the 2022 ASH Annual Meeting. At a median follow-up of 17.5 months, the trial met its primary end point for event-free survival, according to Abramson. The median EFS was not reached (NR) in the liso-cel arm compared with 2.4 months for SOC. Notably, the 18-month EFS rates were 52.6% and 20.8% for liso-cel and SOC, respectively, Abramson adds.

Furthermore, liso-cel elicited a complete response rate of 74% vs 43% with SOC, Abramson says. The median progression-free survival with liso-cel was NR vs 6.2 months with SOC. Liso-cel also resulted in a numerical improvement in overall survival (OS) compared with SOC (NR vs 29.9 months), although these data were not statistically significant, Abramson notes.

Since patients from the SOC arm were permitted to cross over to the liso-cel arm, investigators conducted a supportive OS analysis to account for patient crossover, Abramson adds. Data from the supportive analysis showed a significant improvement for OS with liso-cel vs SOC, with a stratified hazard ratio of 0.415, Abramson says. The analysis provided further evidence of the benefit of liso-cel compared with SOC in the second-line treatment of patients with LBCL, Abramson concludes.

Videos

Jeremy Abramson, MD, discusses the efficacy data of second-line lisocabtagene maraleucel vs standard-of-care salvage chemotherapy followed by autologous stem cell transplant from the phase 3 TRANSFORM trial done in patients with relapsed/refractory large B-cell lymphoma.

Dr Abramson on the Efficacy of Second-line Liso-cel Vs SOC in Relapsed/Refractory LBCL

Jeremy S. Abramson, MD, director, Jon and JoAnn Hagler Center for Lymphoma, Massachusetts General Hospital, associate professor of medicine, Harvard Medical School, discusses the FDA approval of lisocabtagene maraleucel (liso-cel; Breyanzi) in refractory large B-cell lymphoma.

On February 5, 2021, the FDA approved liso-cel for the treatment of adult patients with certain types of large B-cell lymphoma who have not responded to, or who have relapsed after, at least 2 other types of systemic treatment. The approval of the CD19-directed product offers another highly effective option to patients, says Abramson. 

The regulatory decision was based on findings from the phase 1 TRANSCEND NHL 001 trial in which liso-cel induced an objective response rate of 73% and a complete response rate of 53% in patients with heavily pretreated large B-cell lymphoma. Moreover, the median time to first complete response or partial response was 1 month, suggesting patients can obtain rapid responses with liso-cel, explains Abramson. The median duration of response had not yet been reached at a median follow-up of 12 months, concludes Abramson. 

Jeremy S. Abramson, MD, discusses the FDA approval of lisocabtagene maraleucel in refractory large B-cell lymphoma.  



Dr. Abramson on the FDA Approval of Liso-Cel in Refractory Large B-Cell Lymphoma 

Jeremy S. Abramson, MD, director, Jon and JoAnn Hagler Center for Lymphoma, Massachusetts General Hospital, associate professor of medicine, Harvard Medical School, discusses the results of the multicenter phase I TRANSCEND NHL 001 study evaluating the safety and efficacy of lisocabtagene maraleucel (liso cel) in relapsed/refractory large B-cell lymphoma.

Among 268 patients treated with liso-cel, 255 were evaluable for efficacy. The overall response rate was 73% (95% CI, 67&#8210;78), and the complete response (CR) rate was 53% (95% CI, 47&#8210;59).

At a median follow-up of 10.8 months, the median duration of response (DOR) was 13.3 months (95% CI, 8.2&#8210;not reached [NR]) in the general population. The median DOR was not reached in patients who achieved CR (13.3&#8210;NR). Additionally, the median progression-free survival was 6.8 months (95% CI, 3.3&#8210;11.8), and the median overall survival was 19.9 months (95% CI, 10.9&#8210;NR).

Liso-cel was generally well tolerated among patients, says Abramson. A safety analysis showed 79% of patients experienced grade ≥3 treatment-emergent adverse events, and 42% of patients experienced any grade cytokine release syndrome (CRS).

Nineteen percent of patients received tocilizumab (Actemra) and 21% received corticosteroids for CRS/neurologic events.

Overall, liso-cel elicited an unprecedented rate of durable CRs with low rates of severe toxicity, concludes Abramson.

Jeremy S. Abramson, MD, discusses the results of the multicenter phase I TRANSCEND NHL 001 study evaluating the safety and efficacy of lisocabtagene maraleucel in relapsed/refractory large B-cell lymphoma.

Dr. Abramson on the TRANSCEND NHL 001 Trial in Large B-Cell Lymphoma

Jeremy S. Abramson, MD, clinical director, Center for Lymphoma, Massachusetts General Hospital, discusses the pivotal safety and efficacy results from phase I TRANSCEND NHL 001 trial of lisocabtagene maraleucel (liso-cel) in patients with relapsed/refractory large B-cell lymphoma.

View more from the 2019 ASH Annual Meeting

Dr. Abramson on Safety and Efficacy of Liso-Cel in Relapsed/Refractory Large B-Cell Lymphoma

Jeremy S. Abramson, MD, clinical director, Center for Lymphoma, Massachusetts General Hospital, discusses lisocabtagene maraleucel (JCAR017; liso-cel) as a treatment for patients with non-Hodgkin lymphoma (NHL).

The TRANSCEND trial is currently evaluating the CD19-directed chimeric antigen receptor (CAR) T-cell therapy liso-cel in patients with high-risk diffuse large B-cell lymphoma (DLBCL). This CAR T-cell therapy is showing promising response rates in this population. Abramson says that when the product is collected, the CD4 and CD8 cells are separated and then are separately transduced and expanded. They are then administered back to patients in a 1:1 ratio. This results in a fixed precise dose of CD4 and CD8 CAR-positive T cells administered to every patient.

Findings presented at the 2018 ASCO Annual Meeting showed a complete response rate of 46% (95% CI, 30%-63%) at 6 months, as well as an ongoing objective response rate of 49% (95% CI, 32%-66%). At the time of report, the median overall survival (OS) had not been reached among patients who achieved a CR at the pivotal dose, but the 12-month OS rate in these patients was 89% (95% CI, 72%-96%). 

Jeremy S. Abramson, MD, clinical director, Center for Lymphoma, Massachusetts General Hospital, discusses lisocabtagene maraleucel (JCAR017; liso-cel) as a treatment for patients with non-Hodgkin lymphoma. 

Dr. Abramson Discusses Lisocabtagene Maraleucel in NHL

Jeremy S. Abramson, MD, clinical director, Center for Lymphoma, Massachusetts General Hospital, discusses the TRANSCEND study, which is exploring the CD19-directed chimeric antigen receptor (CAR) T-cell therapy JCAR017 in patients with relapsed/refractory aggressive B-cell non-Hodgkin lymphoma (NHL).

TRANSCEND is a phase I multicenter trial looking at the dose and safety of this cellular therapy in patients with diffuse large B-cell lymphoma and mantle cell lymphoma, Abramson says. JCAR017 has a 41BB co-stimulatory domain and a truncated EGFR receptor used to track the product in circulation and in tissue.

In the study, patients all receive a defined composition product of 1:1 of CD4 and CD8 anti-CD19 CAR T cells with JCAR017. Researchers are enrolling high-risk patients with these lymphomas who mostly are refractory to chemotherapy.

Jeremy Abramson, MD

Articles

Dr Abramson on the Efficacy of Second-line Liso-cel Vs SOC in Relapsed/Refractory LBCL

Dr. Abramson on the FDA Approval of Liso-Cel in Refractory Large B-Cell Lymphoma

Dr. Abramson on the TRANSCEND NHL 001 Trial in Large B-Cell Lymphoma

Dr. Abramson on Safety and Efficacy of Liso-Cel in Relapsed/Refractory Large B-Cell Lymphoma

Dr. Abramson Discusses Lisocabtagene Maraleucel in NHL

Dr. Abramson on TRANSCEND on JCAR017 Therapy in NHL