US approves BMS CAR-T in large B-cell lymphoma

Samit Hirawat, medical director of Bristol Myers Squibb.

Bristol Myers Squibb has announced that the US Drug Evaluation Agency (FDA) has approved Breyanzi (lisocabtagene maraleucel; lisa-cel), a CD19-targeted chimeric antigen receptor (CAR) T-cell therapy for the treatment of adult patients with large B-cell lymphoma (DLB), including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma of grade 3B that have:

  • Disease refractory to first-line chemoimmunotherapy or has relapsed within 12 months of first-line chemoimmunotherapy

  • Disease refractory to first-line chemoimmunotherapy or who have relapsed after first-line chemoimmunotherapy and are not candidates for hematopoietic stem cell transplantation (HSCT) due to comorbidities or age

With these two new indicationslisa-cel already has the widest spectrum of suitable patients among cell therapies CAR-T in relapsed or refractory LCBG. Liso-cel is not indicated for the treatment of patients with primary lymphoma of the central nervous system.

therapy has been shown clinically relevant and statistically significant improvements in event-free survival (EFS), complete responses (CR), and progression-free survival (PFS) compared to standard of care in patients with primary refractory or relapsed BCCL within 12 months of treatment From first line. An improvement in the SLA represents an increase in the time that patients remain alive and without disease progression or the need for additional treatment.

Liso-cel, a differentiated CAR-T cell therapy, is composed of the T lymphocytes from the patient, which are removed and genetically modified to become CAR-T cells, which are then infused as a one-time treatment. can be managed in the hospital or outpatient setting in a certified treatment center.

“As part of our commitment to developing innovative cancer treatments for patients with essential needs to cover, lisa-cel is a potentially curative option for more patients”, he declared. Esther Bank, vice president and general manager of US Hematology at Bristol Myers Squibb. “Based on its demonstrated clinical benefit, this approval underscores thes significant progress what we are doing to fulfill the promise of cell therapy.”

LCBG is an aggressive and difficult-to-treat blood cancer, and up to 40 percent of patients have disease that is refractory or relapses after initial treatment. Historically, the only chance of cure for these patients was the current standard treatment consisting of intensive salvage immunotherapy in the hospital setting followed by high-dose chemoimmunotherapy and HSCT in those whose disease responds to salvage treatment. However, half of the patients are not considered candidates to receive a stem cell transplant because of their age and/or comorbidities, and it is estimated that only 25 percent of those who are candidates can receive a stem cell transplant and obtain long-term clinical benefit. For patients who are not considered candidates for stem cell transplantation, treatment options are limited. If left untreated, patients with relapsed or refractory DLBCL have a life expectancy of only three to four months.

Liso-cel represents a remarkable advance over the treatment that has been the reference for almost 30 years, providing significantly improved efficacy with a well-established safety profile. Manali Kamdar, Principal Investigator of the Transform Study and Associate Professor and Clinical Director of the Lymphoma Service in the Division of Hematology, Hematologic Malignancies and Stem Cell Transplantation at the University of Colorado Cancer Center. “This important milestone reinforces the benefit of offering patients earlier A CAR-T cell treatment option is on their treatment journey and it is essential that we start working to implement this therapy into standard practice as a second-line treatment to help improve outcomes for more patients.”

“Large B-cell lymphoma patients whose disease does not respond or who relapse after first-line treatment often face long and intense courses of chemotherapy with the goal of undergoing stem cell transplantation,” he notes. Lee Greenberger, scientific director of the Leukemia and Lymphoma Society (LLS). “As an early supporter of CAR-T since the 1990s, LLS is excited about FDA approval of a CD19-targeted CAR-T cell therapy that has moved from late-line therapy to a second-line option, offering patients with relapsed or refractory large B-cell lymphoma the possibility of a long-term remission and the hope of healing.


CAR-T evaluated in a large sample of patients

Liso-cel is the only CAR T cell therapy that has been evaluated in a large patient population in second-line for LCBG in two different company-sponsored studies, which included patients whose disease had relapsed during or within 12 months of first-line treatment and regardless of their transplant candidacy.

Approval of the expanded indications for lisa-cel is based on results from the pivotal Phase 3 Transform study in which adults with GBCL who were primary refractory or who relapsed within 12 months of first-line treatment were randomly assigned to receive either lisa-cel or the standard of care consisting of salvage immunochemotherapy and, if they respond, high-dose chemotherapy and HSCT. The trial included patients with different histologic subtypes and high-risk featuresand featured a patient-centered design, allowing bridging immunochemotherapy in the lisso-cel group for disease control, reflecting real-life clinical practice and allowing inclusion of patients with more aggressive disease and with a faster progression.

Due to the high rate of patients whose disease does not respond to salvage immunochemotherapythe trial also allowed for crossover from the reference treatment arm to the lisso-cel arm, if patients did not have a response after three cycles of salvage chemotherapy or had disease progression during that time.

The results of the Transform study showed that lyso-cel (n=92) was more than four times the median DFS from reference treatment (n=92) (10.1 months vs. 2.3 months [HR: 0,34; IC del 95 por ciento (0,22-0,52) p<0,0001]). The majority of patients achieved a CR with lisa-cel compared with less than half who achieved it with standard treatment (66 percent [IC del 95 por ciento: 56 por ciento – 76 por ciento] versus 39 percent [IC del 95 por ciento: 29 por ciento – 50 por ciento]; p

The results also showed that lisa-cel achieved a PFS greater than double that achieved with standard of care (median PFS: 14.8 months vs. 5.7 months [HR: 0,41; IC del 95 por ciento: 0,25-0,66; p=0,0001]). In the study, nearly all patients (97 percent) in the lisso-cel group received treatment versus less than half (47 percent) of patients who completed high-dose chemotherapy and autologous HSCT in the lisso-cel group. reference treatment.

The efficacy of lisa-cel in the second-line setting was also based on data from the phase 2 PILOT study, in which 61 adults with relapsed or refractory primary GBCL who were not considered candidates for stem cell transplantation were treated with smooth-cel. Pilot study included a large patient population depending on age, general condition and/or organic function and comorbidities, and regardless of time to relapse after first-line treatment. smooth-cel showed deep and lasting answers, with an overall response rate of 80 percent, the study’s primary endpoint, and a CR rate of 54 percent, with a median time to CR of one month (range: 0.8 – 6, 9 months). The median duration of response was 11.2 monthswith a median duration of response not reached in those patients who presented a CR.

Liso-cel has a well-established safety profile and according to the results of the Transform and Pilot studies, the cases of SLC and neurological events were generally low grade and were mostly resolved quickly with standard protocols and without the use of prophylactic corticosteroids. CRS of any grade was reported in less than half of patients (45 percent; 68/150), with grade 3 being reported in 1.3 percent of patients.

Neurological events reported any grade in 27 percent (41/150) of patients treated with lisso-cel, being grade 3 in 7 percent of patients. The median time to CRS onset was 4 days (range: 1 to 63 days) and the median duration of CRS was 4 days (range: 1 to 16 days). The median time to onset of neurological events was eight days (range: 1 to 63 days). The median duration of these toxicities it was six days (range: 1 to 119 days). The delay in the onset of CRS and neurological events allowed the option of outpatient treatment and management of patients. In addition, the clinical profile of lisa-cel supported its use in a wide range of patients with relapsed or refractory DLBCL.

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