ABSTRACT
Introduction 939 Aggressive lymphoma 940 Second-line treatment before the rituximab era 940 Second-line treatment with rituximab 940 Rituximab and other chemotherapy regimens 942 Monoclonal antibodies in aggressive lymphoma 942 Radioimmunotherapy 943 Concomitant chemoradiotherapy 943 Follicular lymphoma 943 Monoclonal antibodies in low-grade lymphoma 944 Radiation therapy and radioimmunotherapy in 944
low-grade lymphoma Mantle cell lymphoma 945
Chronic lymphocytic leukemia and small lymphocytic 945 lymphoma
Monoclonal antibodies 945 Lymphoplasmacytoid lymphoma and Waldenström 946
macroglobulinemia Marginal zone lymphoma 946 Hodgkin lymphoma 946 T cell lymphoma 947 Cutaneous T cell lymphoma 948 Future directions 948 Key points 948 References 948
Progress in the treatment of lymphoid malignancies obtained with multiagent chemotherapy has been dramatic for almost all the different histologic subtypes. By combining chemotherapy and monoclonal antibodies complete remission (CR) with disease disappearance can now be achieved in 50 percent to 90 percent of the patients, with the percentage variation reflecting histology and stage. However, two different situations induce treatment modifications and use of a salvage regimen: resistant disease, which is characterized as having a dismal or ephemeral response at the end of first-line therapy, or relapses after CR and then fails to respond to salvage therapy; and partial response (PR), which is defined as an objective response less than CR. The time at which the response is evaluated varies from one lymphoma subtype to another and, for chronic lymphoproliferative disorders, achieving a measurable PR could be the initial goal. In many situations in younger patients, salvage treatment in a chemosensitive patient is followed by high-dose therapy (HDT) and autologous stem cell transplantation (ASCT). Thus, the reported outcomes of salvage treatment have included two entities: efficacy of alternative treatment and the impact of HDT
Lymphoid malignancies are among the few neoplastic diseases for which salvage therapy can significantly prolong survival. The choice of which regimen should be administered for relapsing lymphoid malignancies depends on the type of disease (chronic or acute), prognostic factors at the time of relapse, and the general strategy according to age and whether or not the patient is eligible for stem cell transplantation. Numerous old and new drugs are available to treat patients and their efficacies have mostly been evaluated in nonrandomized studies. Obviously, the difficulty of obtaining a cure or a prolonged disease-free period with salvage conventional chemotherapy can explain the numerous phase II studies. The response rate is assessed within 30 days of completing treatment according to the International Harmonization Project criteria, which were recently revised to include the use of positron emission tomography (PET) scanning.1 Moreover, very often results are reported only in abstracts and not followed by peerreviewed publications. More recently, the addition of monoclonal antibodies – radiolabeled or not – has brought new insights into the design of salvage treatments. Amazingly, the benefits of the chemotherapy-immunotherapy combinations were demonstrated in first-line randomized trials before the completion of studies on relapsing patients. One
antibody treatments after prior exposure to such products. More patients are now being treated beyond their first relapses and cumulative doses or toxicities must be considered in the management of these patients. This problem can be crucial for patients with chronic lymphoproliferative disorders who can survive more than 10 years and whose treatments will expose them to enhanced risk of developing second cancers, solid tumors, or myelodysplastic syndromes. This risk also exists for patients with high potential cure rates such as those with Hodgkin lymphoma, who, at 15 years, run equal risks of dying of Hodgkin lymphoma or late adverse effects of therapy. Due to the wide spectrum of diseases, salvage regimens are reviewed disease by disease and questions of general or specific approaches are raised at that time. This chapter does not deal with ongoing experimental studies and is restricted to the wide variety of agents already registered or well on their way to being approved.
