How I treat relapsed classical Hodgkin lymphoma after autologous stem cell transplant

Abstract

Despite the success of standard front-line chemotherapy for classical Hodgkin lymphoma (cHL), a subset of these patients, particularly those with poor prognostic factors at diagnosis (including the presence of B symptoms, bulky disease, advanced stage, or extranodal disease), relapse. For those patients who relapse following autologous stem cell transplant (SCT), multiple treatment options are available, including single-agent chemotherapy, combination chemotherapy strategies, radiotherapy, the immunoconjugate brentuximab, checkpoint inhibitors nivolumab and pembrolizumab, lenalidomide, everolimus, or observation in selected patients. In patients with an available donor, allogeneic SCT may also be considered. With numerous treatment options available, we advocate for a tailored therapeutic approach for patients with relapsed cHL guided by patient-specific characteristics including age, comorbidities, sites of disease (nodal or organ), previous chemosensitivity, and goals of treatment (long-term disease control vs allogeneic SCT).

Emerging treatment options for the management of Hodgkin's lymphoma: clinical utility of Nivolumab

“…In selected cHL patients with relapsed or refractory disease after ASCT, allogeneic SCT can provide potential durable disease control with similar PFS and OS seen with either myeloablative or reduced intensity conditioning regimens 29,93. PD-1 inhibition has been shown in preclinical models to augment acute GVHD due to T-cell disinhibition, raising concern regarding the safety of checkpoint inhibition in patients who are either being considered for allogeneic SCT or who have relapsed after allogeneic transplant 94,95.…”

Five-year follow-up of brentuximab vedotin combined with ABVD or AVD for advanced-stage classical Hodgkin lymphoma

“…[4][5][6] In multisystemic, severe forms of this disease, targeted treatments with the BRAF inhibitors, vemurafenib and dabrafenib, have been efficiently used in BRAF-mutated patients. [7][8][9] In wild-type (WT) BRAF patients, cobimetinib, a MEK inhibitor, has also been used with success.…”

“…[1][2][3][4][5][6] However, treatment of patients with advanced-stage disease with optimal chemotherapy, such as doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), fails to cure as many as 15% to 25% of patients, necessitating secondary intensified treatment, which incurs major toxicity and is only successful in ;50% of patients. 1,7,8 Genuine improvement in these outcomes will require identification of novel effective agents that can be integrated with standard chemotherapy during primary treatment. One candidate agent is brentuximab vedotin (ADCETRIS, Seattle Genetics, Inc), an antibody drug conjugate that employs a protease cleavable covalent linker to combine a chimeric monoclonal antibody directed against the CD30 antigen found universally on the surface of Hodgkin Reed-Sternberg cells with monomethyl auristatin E, a microtubule disrupting agent.…”

Long-Term Responders After Brentuximab Vedotin: Single-Center Experience on Relapsed and Refractory Hodgkin Lymphoma and Anaplastic Large Cell Lymphoma Patients

“…Nowadays, the standard treatment for patients with Hodgkin lymphoma (HL) who are unresponsive to upfront therapy or who relapse after primary treatment consists of salvage chemotherapy (aimed at harvesting autologous stem cells from peripheral blood) followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT) [1,2]. Approximately 40%-65% of patients with systemic anaplastic large cell lymphoma (sALCL) develop recurrent disease after front-line therapy [3].…”

“…Given that most patients with relapsed and refractory HL or sALCL are scheduled to undergo a highly toxic high-dose chemotherapy regimen, any strategy aimed at achieving a minimal disease status, and at specifically obtaining a positron emission tomography (PET)-negative status before ASCT without severe toxicity, would represent a major advance in the overall management of these patients. Furthermore, although ASCT has yielded a long-term progression-free The Oncologist 2016;21:1436-1441 www.TheOncologist.com ©AlphaMed Press 2016 survival (PFS) in 50%-60% of patients with chemosensitive relapse, the outcomes remain poor among those with primary chemorefractory disease, where long-term survival rarely exceeds 15%-17% [1]. In fact, disease recurrence still remains the principal cause of ASCT failure, and early disease progression after transplant (i.e., within 6 months from high-dose conditioning) emerges as the most important predictor of unfavorable outcome.…”