Lisocabtagene maraleucel obtains fda approval as a second-line treatment for rrLBCL

03 Sep 2022

Lisocabtagene maraleucel (liso-cel), a cell-based gene therapy was approved as a second-line treatmentof relapsed or refractory (rr) large B-cell lymphoma (LBCL) in adult patients by the United States (US)Food and Drug Administration (FDA).1 Liso-cel is an autologous and chimeric antigen receptor T-cell (CAR-T)therapy that specifically directs cytotoxicity to CD19 antigen-presenting B cells.2,3 First approved inFebruary 2021, liso-cel treats certain types of LBCL, including diffuse LBCL (DLBCL), high-grade B-celllymphoma, primary mediastinal B-cell lymphoma, and follicular lymphoma grade 3B.2,3 Two new indicationshave been given to liso-cel for the LBCL treatment in patients who have refractory disease to thefirst-line immunochemotherapy, or refractory disease or relapse after the first-line immunochemotherapy.1,3The approval of liso-cel was supported by the TRANSFORM phase 3 study, which illustrated the efficacyand safety of the therapy as a second-line treatment for rrLBCL.1,3

While the first-line LBCL treatment with rituximab and anthracyclineimmunochemotherapy has been proven to be effective for cureor remittance in most patients, some still need to resort to thesecond-line approaches if they experience refractory disease orrelapse.3 The standard second-line treatment for rrLBCL consists ofplatinum-based salvage immunochemotherapy, high-dose chemotherapy,and autologous hematopoietic stem-cell transplantation (HSCT).3The emergence of CAR-T therapy has become a promising stepforward in developing curative treatments for rrLBCL, and thatmany clinical trials have shown that survival and response ratesincreased after the CAR-T therapy.4 Based on the TRANSFORMtrial, liso-cel demonstrated favorable efficacy and safety profiles asa second-line LBCL treatment, which included DLBCL, high-gradeB-cell lymphoma, primary mediastinal B-cell lymphoma, and follicularlymphoma grade 3B, contributing to its broad patient eligibility.1,3

TRANSFORM is an ongoing pivotal, open-label phase 3 study thatcompares the efficacy and safety of liso-cel as a second-line therapy tothe current standard of care (SoC) for rrLBCL patients.3 The trial has beenconducted globally with 47 sites in the US, Europe and Japan, recruitinga total of 184 HSCT-eligible patients at 18-75 years old.3 Enrolled patientswere randomly assigned 1:1 to the liso-cel arm or the SoC arm.3 Theliso-cel group was administered 100 × 106 CAR-T cells intravenously,while the SoCgroup was delivered salvage immunochemotherapy, alsointravenously.3 Patients of the SoC arm received salvage therapy cycles ofR-DHAP (rituximab, cytosine arabinoside, cisplatin, dexamethasone),R-ICE (rituximab, ifosfamide, carboplatin, etoposide), or R-GDP (rituximab,gemcitabine, cisplatin, dexamethasone), prior to high-dose chemotherapyand autologous HSCT.3

The primary endpoint of the TRANSFORM trial was event-freesurvival (EFS) per independent review committee (IRC), with a medianfollow-up period of 6.2 months.3 The median EFS of the liso-celgroup was 10.1 months (95% CI: 6.1-not reached), a significant 4-foldincrease compared with 2.3 months (95% CI: 2.2-4.3) of the SoCgroup, indicating the clinical benefit of liso-cel over the current SoCin all analyzed subgroups.3 The key secondary endpoints relating toclinical efficacy included complete response (CR) rate, progression-freesurvival (PFS) per IRC, and overall survival (OS).3 The liso-cel group alsodemonstrated a 27% increase in CR rate and 2.5-fold in median PFS,supporting the superiority of liso-cel treatment compared with thesecond-line SoC treatment.3

The safety of liso-cel was assessed through the secondary safetyoutcomes concerning the types, frequency and the severity of adverseevents (AEs), as well as laboratory abnormalities, and hospital resourceuse.3 The most common AEs reported during the TRANSFORM trialwere neutropenia, anemia and thrombocytopenia, along with fewincidences of severe grade 3 or above cytokine release syndromeand CAR-T therapy-associated neurological events.3 AEs of any gradeaffected 48% of patients in both the liso-cel group and the SoCgroup, but no treatment-related deaths were reported in the liso-celgroup.3 Liso-cel demonstrated a manageable and established safetyprofile in rrLBCL patients during this study.3

Though the clinical efficacy and safety of liso-cel treatment in rrLBCLpatients have been proven, the TRANSFORM trial had a medianfollow-up period of only 6.2 months.3 Therefore, future studies withlonger follow-up time should be performed to ensure the satisfactoryperformance of liso-cel treatment in the long term.3 Nonetheless,the TRANSFORM trial has demonstrated that the liso-cel treatmentis a superior second-line therapy in comparison to the current SoC,supporting the FDA’s approval of it as a second-line treatment optionfor rrLBCL.1,3

Get access to our exclusive articles.