Diffuse large B-cell lymphoma (DLBCL) is the most common type of aggressive non-Hodgkin lymphoma, often presenting with rapidly growing lymph nodes or masses in various parts of the body. Treating DLBCL requires a thoughtful and individualized approach, starting with accurate classification and proceeding through a combination of systemic therapies, supportive care, and emerging treatment strategies.

When I first assess a patient with suspected DLBCL, I prioritize a complete diagnostic workup. This includes excisional lymph node biopsy to confirm the diagnosis and immunophenotyping to differentiate it from other B-cell lymphomas. PET-CT imaging, bone marrow biopsy, and molecular testing such as MYC, BCL2, and BCL6 rearrangements help determine the disease subtype and prognosis. Determining whether the patient has germinal center B-cell (GCB) or activated B-cell (ABC) subtype provides insight into potential outcomes and therapeutic direction.

For most newly diagnosed patients with DLBCL, frontline therapy still revolves around the standard R-CHOP regimen, which includes rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone. This protocol is typically administered over six cycles, every 21 days. R-CHOP has cured a significant percentage of patients, particularly those with localized disease or favorable risk profiles.

Patients with bulky disease, double-hit lymphoma (with MYC and BCL2/BCL6 rearrangements), or high International Prognostic Index (IPI) scores may require a more aggressive approach. In these cases, I may consider dose-adjusted EPOCH-R, which intensifies the chemotherapy while still incorporating rituximab. For high-risk patients, especially younger individuals, consolidative autologous stem cell transplant after initial therapy may be part of the plan.

Regular imaging and clinical evaluation during and after treatment help assess response. I relyon interim PET-CT scans to guide decisions mid-therapy. A complete metabolic response after a few cycles is generally associated with better outcomes, and patients with persistent uptake may need further assessment with biopsy or alternative therapy planning.

If the disease relapses or proves refractory, I evaluate eligibility for second-line therapies. Options here include salvage chemotherapy regimens such as R-ICE or R-DHAP, followed by autologous stem cell transplantation in suitable patients. More recently, CAR T-cell therapy has emerged as a major treatment option for relapsed or refractory DLBCL, particularly in those who have failed at least two prior lines of therapy. Axicabtagene ciloleucel and lisocabtagene maraleucel are among the approved CAR T therapies showing promising results in this setting.

For patients who may not tolerate aggressive therapies, I consider targeted agents such as polatuzumab vedotin (in combination with bendamustine and rituximab) or tafasitamab with lenalidomide. These regimens offer viable options for older or frail patients while still providing disease control.

Supportive care plays a crucial role in managing side effects and maintaining treatment adherence. I monitor for febrile neutropenia, cardiac toxicity from anthracyclines, and peripheral neuropathy. Prophylactic growth factors, cardiac monitoring, and dose adjustments help manage these risks.

Long-term follow-up focuses on monitoring for relapse, late effects of chemotherapy, and secondary malignancies. I provide survivorship care that includes regular blood work, imaging when indicated, and attention to psychosocial health.

Treating DLBCL is not a one-size-fits-all process. With each patient, I balance clinical factors, pathology, patient preferences, and evolving research to create a treatment strategy that aims for cure while preserving quality of life.