A new era for transplant-ineligible R/R LBCL patients: what’s changing?

Most patients with large B-cell lymphoma (LBCL) are cured with frontline chemoimmunotherapy; however, 30-40% experience relapsed or refractory (R/R) disease. Historically, salvage chemotherapy followed by autologous stem cell transplantation (ASCT) represented the standard second-line treatment. Several studies have demonstrated that patients with primary refractory or early-relapsed LBCL derive limited benefit from ASCT. With the advent of chimeric antigen receptor (CAR) T-cell therapy, the prognosis of R/R LBCL has changed substantially. The TRANSFORM and ZUMA-7 trials, which showed superior efficacy and manageable toxicity, led to the approval of lisocabtagene maraleucel (liso-cel) and axicabtagene ciloleucel (axi-cel) as second-line options. Importantly, these trials required participants to be medically fit for ASCT. This review focuses on therapeutic options for transplant-ineligible patients with R/R LBCL. The phase II PILOT study demonstrated that liso-cel is effective in medically unfit individuals, supporting the definition of a distinct category of ASCT-ineligible patients. Additional active options include antibody-drug conjugates, bispecific antibodies in combination with chemotherapy, and other novel immunotherapies, which have shown promising response rates in this difficult-to-treat population.