The treatment paradigm for large B-cell lymphoma (LBCL) has undergone significant changes in recent years. Patients who fail to achieve a complete response (CR) after first-line therapy (1L) or relapse within 12 months are considered to have a poor prognosis. For these individuals, newer therapeutic options such as CAR-T cell therapy or immunoconjugates have largely replaced traditional approaches like chemotherapy, autologous hematopoietic stem cell transplantation (auto-HCT), or best supportive care. Accurate staging and evaluation of treatment response are critical, especially for patients achieving a partial response (PR) at the end of 1L. Patients with PR represent a distinct and less well-defined subgroup compared to those with stable or progressive disease or those achieving CR. These patients often have better outcomes than those with progressive disease or stable disease, yet their management remains less straightforward. Prognostic classifications and treatment guidelines continue to evolve, offering new perspectives on how best to approach this subset. While immunotherapy with anti-CD19 CAR-T cells has become the standard of care for refractory LBCL, the role of salvage therapies may still be relevant for patients with PR who are not fully chemorefractory. This review underscores the importance of refining the definitions, prognostic assessments, and therapeutic strategies for patients with partial response or early relapse, aiming to optimize outcomes in this challenging clinical context.