The landscape of treating diffuse large B-cell lymphoma (DLBCL) has seen significant advancements, particularly with the introduction of chimeric antigen receptor (CAR) T-cell therapy. Traditionally, patients undergo induction chemotherapy regimens like R-CHOP or R-EPOCH. However, recent developments have introduced pola-R-CHP for specific subtypes and advanced cases. For those who relapse or are refractory to initial treatments, CAR T-cell therapy has emerged as a promising option, especially for early relapses. Additionally, autologous hematopoietic cell transplant remains viable for later relapses. The emergence of new agents like loncastuximab tesirine and selinexor further expands therapeutic options. Importantly, minimal residual disease (MRD) assessment is crucial in predicting response and guiding treatment plans.

In the evolving field of DLBCL management, the approach to treating this aggressive form of non-Hodgkin lymphoma has shifted significantly. Initial therapies typically involve standard induction chemotherapy protocols. These include combinations such as rituximab with cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone (R-CHOP), or rituximab with etoposide phosphate, vincristine sulfate, cyclophosphamide, doxorubicin hydrochloride, and prednisone (R-EPOCH). More recently, polatuzumab vedotin combined with rituximab, cyclophosphamide, doxorubicin hydrochloride, and prednisone (pola-R-CHP) has been approved for patients with activated B-cell subtype and high-risk factors.

For patients experiencing relapsed or refractory DLBCL, the therapeutic strategy changes. Historically, outcomes were poor for those resistant to chemotherapy, with cure rates hovering around 7%. The advent of CAR T-cell therapy has transformed this outlook. Patients who relapse within a year of initial treatment or show refractory disease benefit greatly from CAR T-cell therapy, which offers cure rates of approximately 40% at a seven-year follow-up. This therapy involves genetically modifying a patient's T-cells to target cancer cells more effectively, providing hope where traditional methods fail.

Another critical aspect of managing DLBCL is the use of MRD assessment. This technique evaluates the presence of residual cancer cells after treatment. Patients with positive PET scans but negative MRD assessments may not require additional aggressive treatments. Conversely, persistent MRD positivity can signal potential refractory disease, allowing clinicians to plan for alternative therapies sooner. Early detection through MRD helps tailor personalized treatment strategies, improving patient outcomes.

Despite these advances, challenges remain. Bridging therapies may be necessary while preparing for CAR T-cell therapy due to the time required for product manufacturing. Factors like housing and transportation can also pose logistical hurdles. Nonetheless, the majority of eligible patients opt for CAR T-cell therapy, recognizing its potential benefits. Academic centers play a crucial role in administering these treatments, emphasizing the importance of timely referrals and comprehensive evaluations.

The introduction of CAR T-cell therapy and other novel agents marks a transformative period in DLBCL treatment. While initial induction chemotherapy remains the cornerstone, emerging therapies offer new hope for patients facing relapse or refractory disease. By leveraging MRD assessments and personalized medicine, healthcare providers can better navigate this complex condition, ultimately enhancing patient care and survival rates.