Therapies for Relapsed Hodgkin Lymphoma: Transplant and Non-Transplant Approaches Including Immunotherapy

Abstract

Autologous stem cell transplant remains the standard of care for relapsed Hodgkin lymphoma (HL). Approximately 50% of patients with chemo-sensitive relapse will be cured with this approach. The optimal pretransplant salvage regimen is controversial, but less toxic combinations seem to be equivalent to more aggressive approaches. For patients with chemorefractory disease at relapse and those failing autologous transplant, the long-term prognosis remains poor. New approaches such as reduced-intensity allogeneic transplant, monoclonal antibodies targeting the CD30 antigen, Epstein-Barr virus (EBV)-specific cytotoxic T-lymphocytes, and bortezomib are under investigation, but preliminary results are disappointing. New therapies are needed for patients with relapsed HL.During the last decade, the questions regarding the treatment of relapsed Hodgkin lymphoma (HL) have changed. There is no longer a need to address treatment of relapse after primary radiotherapy, as this approach to HL has virtually disappeared. In addition, controversy surrounding the optimal timing (first vs second relapse) of autologous stem cell transplantation (auto-SCT) after failure of primary chemotherapy (CT) has largely subsided. Results of a large randomized trial from the German Hodgkin Study Group (GHSG) and European Group for Blood and Marrow Transplantation (EBMT) published in 2002 and updated at the American Society of Clinical Oncology (ASCO) 2005 meeting showed freedom from treatment failure was significantly better for patients undergoing transplant compared to non-transplant salvage, regardless of whether they relapsed early (< 12 months) or late following primary chemotherapy. 1,2Novel approaches to the primary treatment of HL and additional options for the treatment of relapsed disease have resulted in new questions.• Should patients who receive chemotherapy alone for early stage disease and have a localized relapse at the site(s) of initial disease receive radiotherapy (RT) or high-dose therapy and transplant at the time of first relapse? • What options are available for patients relapsing after aggressive first-line regimens such as dose-escalated BEACOPP? • Given the marked decrease in mortality following allogeneic transplant with reduced intensity conditioning (RIC), are there circumstances where this approach would be favored over autologous stem cell transplantation? • How should newer agents with activity in HL, such as vinorelbine and gemcitabine, be incorporated into treatment of relapsed disease?Unfortunately, studies are not yet available to answer these questions completely. This review will summarize the recent literature regarding treatment of relapsed HL including prognostic factors, pre-transplant salvage regimens, advances and long-term follow-up of auto-SCT, use of RIC with allogeneic transplant (RIC-allo), and the continued search for new drugs including an active monoclonal antibody for HL. Prognostic FactorsMany prognostic factors have been described for patients relapsing after first-line chemotherapy includi...

Prognostic value of FDG-PET scan imaging in lymphoma patients undergoing autologous stem cell transplantation

“…The median PFS was 19 months (range 2-59 months) in the FDG-PET-negative group and 5 months (range [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] in the FDG-PET-positive group (Po0.001; Figure 1a). The median OS was not reached in the FDG-PET-negative group and was 19 months in the FDG-PET-positive group (P ¼ 0.04; Figure 1b).…”

“…5,6 However, these reports might be subject to selection bias and most clinicians agree that even in HD, response to salvage chemotherapy is highly predictive of outcome after ASCT. 7 Traditionally, conventional computed tomography (CT) scans have been used as the radiographic assessment tool in standardized response criteria in patients with lymphoma. 8,9 Clinical trials that established the benefit of ASCT in chemotherapy sensitive patients used the CT-based response criteria.…”

Fludarabine-melphalan as a preparative regimen for reduced-intensity conditioning allogeneic stem cell transplantation in relapsed and refractory Hodgkin's lymphoma: the updated M.D. Anderson Cancer Center experience

“…However, the prognosis for many patients with relapsed and refractory disease remains poor. [1][2][3][4] Many of them can be successfully salvaged with high-dose chemotherapy and autologous stem cell transplantation (SCT). However, patients who relapse after autologous SCT have a particularly poor prognosis, especially those who are chemorefractory.…”

Bone marrow stem cell damage after three different chemotherapy regimens for advanced Hodgkin's lymphoma

“…Radiotherapy has progressively disappeared from firstline treatment for Hodgkin's lymphoma and multiple-drug chemotherapy now plays the pivotal role in the management of this disease, leaving irradiation only a selected, limited and complementary function. Moreover, it is becoming clear that in most cases, after failure of primary treatment, highdose chemotherapy followed by AuBMT is significantly more effective than non-transplant salvage therapy, regardless of whether the relapse occurs early or late after primary chemotherapy (3,9). Thus, it is likely that the choice of the first-line chemotherapy should be guided not only by the evidence of its efficacy and consideration of its potential late toxicity, but also by whether it enables AuBMT procedures should the first treatment fail.…”