New drugs are continually being researched and developed for Non-Hodgkin’s lymphoma. These must be shown to be safe and effective before doctors can prescribe them to patients. Through clinical trials, researchers test the effects of new drugs on a group of volunteers with non-Hodgkin’s lymphoma. Following a strict protocol and using carefully controlled conditions, researchers evaluate the investigational drugs under development and measure the ability of the new drug to treat non-Hodgkin’s lymphoma,...
Bone marrow transplantation (BMT) is the treatment of choice for patients whose lymphoma has relapsed. Preliminary studies indicate that approximately 20% to 40% of patients will have a long-term disease-free status, but the precise percentage depends on patient selection and the specific treatment used. Preparative drug regimens have varied; some investigators also use total-body irradiation. Similar success has been achieved using autologous marrow, with or without marrow purging, and allogeneic marrow.[2,3,4,5,6]
Evidence (bone marrow transplantation):
In a prospective, randomized study, known as the EORTC-PARMA trial, 215 patients in first or second relapse of aggressive lymphoma, younger than 60 years, and with no bone marrow or central nervous system involvement, were given two cycles of intensive combination chemotherapy. The 109 patients who responded were randomly assigned to receive four more cycles of chemotherapy and involved-field radiation therapy (IF-XRT) versus autologous BMT followed by IF-XRT. With a 5-year median follow-up, the event-free survival (EFS) was significantly improved with transplantation (46% vs. 12%). Overall survival (OS) was also significantly better with transplantation (53% vs. 32%).[Level of evidence: 1iiA] Salvage BMT was unsuccessful for patients on the nontransplant arm whose disease relapsed.
In general, patients who responded to initial therapy and who have responded to conventional therapy for relapse prior to the BMT have had the best results.
In a prospective trial, patients who relapsed late (>12 months after diagnosis) had better OS than patients who relapsed earlier (8-year survival was 29% vs. 13%, P = .001).[Level of evidence: 3iiiA]
Peripheral stem cell transplantation has yielded results equivalent to standard autologous transplantation.[10,11] Even patients who never experienced complete remission with conventional chemotherapy may have prolonged progression-free survival (31% at 5 years) after high-dose chemotherapy and hematopoietic stem cell transplantation if they retain chemosensitivity to reinduction therapy.[Level of evidence: 3iiiDiii] Some patients who relapse after a previous autologous transplantation can have durable remissions after myeloablative or nonmyeloablative allogeneic stem cell transplantation.[13,14]; [Level of evidence: 3iiiDiv]
Evidence (peripheral stem cell transplant):
In a randomized prospective trial, 396 patients with diffuse large B-cell lymphoma in first relapse or who were refractory to first-line therapy received either R-ICE (rituximab, ifosfamide, etoposide, and carboplatin) or R-DHAP (rituximab, dexamethasone, high-dose cytarabine, and cisplatin) followed by autologous stem cell transplantation; there was no difference in 3-year EFS or OS.[Level of evidence: 1iiA]
Re-treatment with standard agents
In general, re-treatment with standard agents rarely produces a cure in patients whose lymphomas relapse. Several salvage chemotherapy regimens are available.[18,19,20]
Rituximab alone can induce responses in 33% of patients with relapsing aggressive lymphoma of appropriate phenotype (CD20-positive).; [Level of evidence: 3iiiDiv]
Radiolabeled anti-CD20 monoclonal antibodies, such as iodine-131 tositumomab and yttrium-90 ibritumomab, induce 60% to 80% response rates in patients with relapsed or refractory B-cell lymphoma.[23,24]; [Level of evidence: 3iiiDiv]
Denileukin diftitox, a fusion protein combining diphtheria toxin and interleukin-2, resulted in a 25% objective response rate in 45 heavily pretreated patients, as evidenced in E-1497 (NCT00003615), for example, with aggressive B-cell NHL (CD25, i.e., interleukin-2 receptor, expression was not correlated with response).[Level of evidence: 3iiiDiv]