My burning issues in aggressive Non Hodgkin’s Lymphoma

Combined-modality treatment with chemo-immunotherapy and radiotherapy produces excellent outcomes in early-stage, non-bulky diffuse large B‑cell lymphoma, and reducing toxicity of therapy is a major concern, especially in elderly patients. In a recent trial, elderly patients with non-bulky (<7.5 cm) in complete metabolic remission after four courses of therapy (rituximab, cyclophosphamide, doxorubicine, vincristine, prednisone [R‑CHOP-14] based) were spared additional chemotherapy and went on to receive four cycles of rituximab only, while all other patients continued on chemo-immunotherapy. The 2‑year overall survival was 98%, which matches historical controls. In another analysis from the same trial, elderly patients with bulky disease in positrone emission tomography (PET) based CR (complete remission) after six cycles of chemo-immunotherapy were spared radiotherapy, while PET-positive patients were irradiated. This approach resulted in a significant reduction (42%) of radiotherapy compared to historical controls without compromising efficacy. Radiotherapy could also be omitted in patients of any age with limited stage, non-bulky disease in another trial, with a 5-year event-free survival of 89% and an overall survival of 92%. Another burning issue is enhancing efficacy in relapsed and refractory diffuse large B‑cell lymphoma. Arguably the most exciting approach in this area is chimeric-antigen-receptor T‑cell therapy. Recent trials have shown nearly 10-fold increases in complete responses compared to historical controls, and most importantly, a high percentage (40%) of durable remissions after one year of follow-up. As in other advances in immunotherapy, toxicity is a major concern. Cytokine release syndrome occurs frequently (1–18% grade 3–4) and management is complex, sometimes requiring admission to intensive care and often including the interleukin-6 receptor antibody tocilizumab.