Immunotherapy of NHL cancer

Abstract Non-Hodgkin lymphoma (NHL) encompasses a heterogeneous range of lymphoid neoplasms arising from B cells, T cells, or natural killer (NK) cells. More than seventy subtypes have been identified in NHL, posing considerable difficulties in diagnosis and management due to its significant heterogeneity. While conventional therapies like chemotherapy and radiation have increased survival rates in NHL, they can often lead to relapsed disease or disease resistance to treatment. More recently, immunotherapy has jumped on the scene as a new treatment paradigm in NHL by harnessing the immune system to target and eliminate malignant cells. There have been studies that support the use of monoclonal antibodies in the management of NHL. For example, rituximab, an anti‐CD۲۰ monoclonal antibody, has played a critical role in improved outcomes in patients who received in combination with chemotherapy. Additionally, more recent information suggests that obinutuzumab may outperform rituximab in effectiveness in some populations . A new treatment possibility is the use of bispecific T-cell engagers (BiTEs) =, for example, blinatumomab, is promising in relapsed/refractory populations and has shown efficacy in redirecting T cells to eliminate malignant B cells. Immune checkpoint inhibitors have transformed the landscape of cancer therapies – by targeting mechanisms used by tumors to evade immune detection. Agents like nivolumab and pembrolizumab, which target PD-۱, have proven to be effective therapies for relapsed diffuse large B-cell lymphoma (DLBCL), particularly in PD-L۱ positive patients. Ongoing trials are hopeful in combining PD-۱ inhibitors with chemotherapy to increase overall efficacy. CTLA-۴ inhibitors such as ipilimumab are being evaluated regarding combination therapies with PD-۱ inhibitors for combination regimens to possibly augment immune responses against tumor cells. These combination therapies offer the potential for improved outcomes for patients with NHL. CAR T-cell therapy has resulted in a paradigm shift in management of refractory B-cell malignancies. CAR T cell products, such as axicabtagene ciloleucel, have demonstrated complete remission rates higher than ۵۰% in clinical trials. Unfortunately, toxins such as cytokine release syndrome (CRS) and neurotoxicity arise from CAR T cell therapy. Efforts remain underway to improve CAR T cell designs and management approaches in order to limit toxicity while still providing efficacy. Immunotherapy has profoundly transformed the treatment of non-Hodgkin lymphoma and provided new options for patients whom had previously failed therapy. An important area of early stage research will be to define the mechanisms of resistance, determine promising new drug combinations to overcome resistance mechanisms, and thus improve patient outcomes. As you embark on this journey, introducing these therapies to practice will require appropriate and relevant considerations to the individual characteristics of the patient and optimizing treatment course.

کلیدواژه ها:

Non-Hodgkin lymphoma ، Immunotherapy ، Monoclonal antibodies ، CAR T-cell therapy ، Combination therapies