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Second and third line chemotherapy regimens and biologic therapy for relapsing or resistant classical Hodgkin lymphoma

George P Canellos, MD
Section Editor
Arnold S Freedman, MD
Deputy Editor
Alan G Rosmarin, MD


The likelihood of relapse of Hodgkin lymphoma (HL; formerly called Hodgkin's disease) from initial therapy in the current era of systemic or combined modality therapy is approximately 10 to 15 percent for localized HL and 20 to 40 percent for more advanced stages (ie, IIIB or IV), dependent on prognostic factors [1]. Approximately 40 to 50 percent of these relapses will occur in the first 12 months from induction [2,3]. In addition, approximately 10 to 15 percent will have disease resistant to initial therapy [4,5]. Salvage therapy can achieve durable responses and remissions in approximately one-half of these patients. Patients with high risk disease, a second relapse, or progressive, resistant disease are candidates for high dose chemotherapy and autologous hematopoietic cell transplantation (HCT). Patients who relapse following autologous HCT can only achieve palliation with conventional dose chemotherapy. (See "Treatment of relapse of classical Hodgkin lymphoma after initial chemotherapy" and "Hematopoietic cell transplantation in classical Hodgkin lymphoma".)

A number of regimens have been developed which incorporate drugs not used in initial treatment in an attempt to anticipate and avoid resistance while minimizing toxicity. These regimens have been used as second or third line therapy and as cytoreductive regimens prior to high dose chemotherapy. The trials evaluating the use of these regimens will be reviewed here. Some of the less commonly used regimens and newer attempts not mentioned in this topic are summarized in other reviews [6,7]. In addition, the initial treatment of HL is presented separately. (See "Treatment of favorable prognosis early (stage I-II) classical Hodgkin lymphoma" and "Treatment of unfavorable prognosis early (stage I-II) classical Hodgkin lymphoma" and "Initial treatment of advanced (stage III-IV) classical Hodgkin lymphoma".)


Second and third-line chemotherapy combinations generally achieve complete remission (CR) in 30 to 40 percent of patients with aggressive or resistant disease [6]. They are frequently used as cytoreductive agents prior to proceeding to high dose chemotherapy and autologous hematopoietic cell transplantation (HCT). Salvage chemotherapy without progression to high-dose chemotherapy and autologous HCT results in 8- to 10-year overall survival rates of 21 to 27 percent with freedom from treatment failure of 16 percent. (See "Treatment of relapse of classical Hodgkin lymphoma after initial chemotherapy", section on 'Achieving a second complete response'.)

There has been a multitude of regimens designed for relapsing Hodgkin lymphoma (HL). The major new agents incorporated into salvage regimens include ifosfamide, cisplatinum, etoposide, and, most recently, gemcitabine. Although the list of various regimens from single groups or institutions is long, this review will refer exclusively to those regimens that have had a wider application and common acceptable utility. The long-term assessment of salvage regimens has been made difficult because the majority of patients go on to autologous HCT.

The vast majority of patients in community practice with relapsed disease will have had ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) as their primary chemotherapy. The general standards for salvage chemotherapy include any of the regimens mentioned below which are given usually for a minimum of two cycles, although some patients may require more. A potential limitation of excessive chemotherapy is the impairment of the peripheral stem cell collection process which could be compromised by excess bone marrow suppression. However, it appears that more than 60 to 70 percent of patients are able to proceed to HCT after salvage therapy; in general, approximately 40 to 60 percent of those remain in a second remission, especially if they demonstrate sensitivity to salvage chemotherapy.


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Literature review current through: Feb 2017. | This topic last updated: Tue Dec 13 00:00:00 GMT+00:00 2016.
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