Bristol Myers Squibb presented positive findings from the Phase II PILOT study in the patients with R/R Large B-cell lymphoma for whom hematopoietic stem cell transplantation was not intended.
Breyanzi mechanism of action: Immunologic cytotoxicity; T lymphocyte replacements
Breyanzi is a CD-19 directed chimeric antigen receptor (CAR) T cell therapy, administered as a defined composition to reduce the variability of the CD8 and CD4 component dose variability. Breyanzi has a 4-1BB costimulatory domain which enhances the expansion and persistence of the CAR T cells. The US FDA previously approved Breyanzi for treating adult patients with relapsed or refractory LBCL after two or more lines of systemic therapy. As per the data presented at the ASCO 2022 conference, with a median follow up of 12.3 months, the majority of patients treated with Breyanzi (n=61) saw a reduction in disease. It achieved an overall response rate of 80%, followed by 54% of patients achieving a complete response rate. The Responses with Breyanzi were durable, with a median duration of response of 12.1 months at 15.5 months median follow-up. Moreover, in patients who achieved a CR, the median duration of response was 21.7 months. Additionally, the Median progression-free survival with Breyanzi was 9.0 months, and median overall survival has not been reached.
When looking at the safety profile of liso-cel in this study, Breyanzi had a manageable safety profile in the PILOT study, with no new safety signals and low rates of severe cytokine release syndrome (CRS) or neurologic events, and no Grade 4/5 CRS or neurologic events. CRS of any grade was found in 38% of patients.
“For patients with large B-cell lymphoma that is refractory to or relapses after first-line therapy, stem cell transplant has been the only potentially curative treatment option, but the reality is many patients are not candidates for stem cell transplant, leaving limited treatment options.” –Expert Opinion.
“The results from the PILOT study, including the patient-reported outcomes, show that treatment with liso-cel as a second-line therapy offers durable responses with improved quality of life for patients who historically have had a poor prognosis.”– Expert Opinion.
Looking at the encouraging preliminary findings of the PILOT study, we can anticipate that CAR-T cell therapies can fulfill the unmet needs and become a new standard of care for patients in R/R Large B-cell lymphoma after two or more lines of systemic therapy. In the current scenario, mostly CAR-T cell therapies are approved in higher line of settings (more than 3L+), but now the company is expanding its focus to the second-line setting. In terms of LBCL, it has been about 2 decades since this population of high-risk patients had such an effective new therapeutic developed, as salvage chemotherapy has been the only choice for patients who had the primary refractory disease or who relapsed within 1 year of first-line chemotherapy; so there is a high unmet need in this patient pool. This Breyanzi clinical trial not only showed that Breyanzi is more efficacious but is also absolutely manageable concerning its safety profile. Recently, in February 2022, Breyanzi received Priority Review from FDA for the second line-R/R LBCL.
Moreover, the US FDA has also assigned the PDUFA (Prescription Drug User Fee Act) goal date of June 24, 2022. In April 2022, Yescarta got its approval for second-line treatment of large B-cell lymphoma, and it is the first CAR-T in this line of setting for LBCL. Therefore, it will be interesting to watch the uptake of CAR-T cell therapies in the earlier line of setting. Furthermore, if Breyanzi Large B-cell Lymphoma is approved, it can become the second CAR T cell therapy in the second-line setting and be an important treatment option for patients with R/R LBCL.
Companies- AbbVie, Roche (Genentech), Bristol Myers Squibb, Regeneron Pharmaceuticals, Amgen, Incyte Corporation, Merck Sharp & Dohme LLC, Sanofi, IGM Biosciences, Gilead Sciences, Allogene Therapeutics, Sorrento Therapeutics, Novartis, MorphoSys, Kite Therapeutics, Beigene, Seagen, Curocell, TG Therapeutics, and others.