The most common lymphomas in this group are follicular lymphoma, marginal zone lymphomas, and small lymphocytic lymphoma (SLL). The treatment of indolent lymphomas depends on the stage of disease and the clinical status of the patient. A small number of patients have limited disease with only one or two contiguous abnormal lymph node groups and may be treated with localized irradiation with curative intent. However, most patients (85%) with indolent lymphoma have disseminated disease at the time of diagnosis and are not considered curable. Historically, treatment of these patients has not affected overall survival; therefore, treatment is offered only when symptoms develop or for high tumor bulk. Following each treatment response, patients will experience a relapse at traditionally shorter intervals. Some patients will have temporary spontaneous remissions (8%). There are an increasing number of reasonable treatment options for indolent lymphomas, but no consensus exists on the best strategy. Treatment with rituximab (375 mg/m2 intravenously weekly for 4 weeks) is commonly used either alone or in combination with chemotherapy and may be the only agent to affect overall survival in these disorders. Patients should be screened for hepatitis B because rare cases of fatal fulminant hepatitis have been described with the use of anti-CD20 monoclonal therapies without anti-HBV agent prophylaxis. Rituximab is added to chemotherapy regimens including bendamustine; cyclophosphamide, vincristine, and prednisone (R-CVP); and cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) (see Table 39–3). The immunomodulatory agent lenalidomide in combination with anti-CD20 therapy is an alternative option with similar outcomes to chemotherapy. Some patients with clinically aggressive low-grade lymphomas may be appropriate candidates for allogeneic stem cell transplantation with curative intent. The role of autologous hematopoietic stem cell transplantation remains uncertain, but some patients with recurrent disease appear to have prolonged remissions without the expectation of cure.
Patients with mucosa-associated lymphoid tissue tumors of the stomach may be appropriately treated with combination antibiotics directed against H pylori and with acid blockade but require frequent endoscopic monitoring. Alternatively, mucosa-associated lymphoid tissue tumors confined to the stomach can also be cured with whole-stomach radiotherapy.
Patients with diffuse large B-cell lymphoma are treated with curative intent. Most patients are treated with six cycles of immunochemotherapy such as R-CHOP (see Table 39–3). Involved nodal radiotherapy (INRT) may be added for patients with bulky or extranodal disease. About 25% of patients with diffuse large B-cell lymphoma have been identified as “double-protein expressors” with overexpression of MYC and BCL2 proteins by immunohistochemistry. While the outcomes with R-CHOP are inferior, no definitive alternative treatment recommendations can be made at this time. High-grade lymphoma with chromosomal translocations affecting MYC, such as t(8;14), and translocations affecting BCL2, such as t(14;18), also called “double-hit lymphoma,” has a very aggressive course. Patients with this disease may do better with dose-adjusted R-EPOCH as front-line therapy.
Patients with diffuse large B-cell lymphoma or high-grade lymphoma who relapse after initial chemotherapy can still be cured by autologous hematopoietic stem cell transplantation if their disease remains responsive to chemotherapy. For patients who do not respond to second-line chemotherapy, the treatment of choice is chimeric antigen receptor T-cell therapy targeting CD19 with either axicabtagene ciloleucel or tisagenlecleucel, which produces durable complete response rates of ∼40%.
Mantle cell lymphoma is not effectively treated with standard immunochemotherapy regimens. Intensive initial immunochemotherapy including autologous hematopoietic stem cell transplantation has been shown to improve outcomes. Reduced-intensity allogeneic stem cell transplantation offers curative potential for selected patients. The BTK inhibitors ibrutinib and acalabrutinib are active in relapsed or refractory patients with mantle cell lymphoma. For primary central nervous system lymphoma, repetitive cycles of high-dose intravenous methotrexate with rituximab early in the treatment course produce better results than whole-brain radiotherapy and with less cognitive impairment.
Patients with highly aggressive lymphomas (Burkitt or lymphoblastic) require urgent, intense, cyclic chemotherapy in the hospital similar to that given for ALL, and they also require intrathecal chemotherapy as central nervous system prophylaxis.
Patients with peripheral T-cell lymphomas usually have advanced stage nodal and extranodal disease and typically have inferior response rates to therapy compared to patients with aggressive B-cell disease. Autologous stem cell transplantation is often incorporated in first-line therapy. The antibody-drug conjugate brentuximab vedotin has significant activity in patients with CD30 positive peripheral T-cell lymphomas, such as anaplastic large-cell lymphoma.