Optimal Therapy of Advanced Hodgkin Lymphoma

Abstract

Advanced-stage Hodgkin lymphoma (HL) has become a curable disease in the majority of patients. Research during the last decade has challenged chemotherapy with Adriamycin, bleomycin, vinblastine, dacarbazine (ABVD) as the standard of care and debates continue regarding the role of radiation therapy (RT) in this patient population. The incorporation of interim positron emission tomography (PET) imaging and, recently, further characterization of HL on cellular and molecular levels are emerging as tools for treatment stratification and predictors of disease status. Newer targeted therapies have emerged that are very effective in the relapsed setting and are actively being explored as frontline therapy. Lastly, the expanding population of survivors cured of HL outnumbers patients with the disease and needs to be monitored for therapy-related late effects.Therapeutic advances over the past 3 decades have resulted in the cure of the majority of patients with advanced-stage Hodgkin lymphoma (HL). Several questions emerge when considering what constitutes optimal therapy with a balance between a high cure rate and minimizing short-and long-term toxicity. This review focuses on 3 key elements: (1) what is the optimal chemotherapy?; (2) what is the role of radiation therapy (RT) in advanced HL?; and (3) can we adapt therapy based on clinical biological risk factors? What is the optimal chemotherapy?In North America, combination chemotherapy with Adriamycin, bleomycin, vinblastine, dacarbazine (ABVD) is considered the standard of care for advanced HL, providing an excellent balance of efficacy and toxicity. 1 Over the past decade, new regimens have been developed for patients with advanced HL based on the premise of either improved efficacy or reduced toxicity (Table 1). The major challenge to the clinician is how to interpret results from various clinical trials to individualize therapy and achieve a high cure rate while at the same time minimizing acute and late toxicity for patients with advanced HL. Dose-escalated bleomycin, etoposide, doxorubicin (Adriamycin), cyclophosphamide, vincristine (Oncovin), procarbazine, and prednisone (escalated BEACOPP or escB), developed by the German Hodgkin Study Group (GHSG), has emerged as a very effective regimen and yielded significantly better survival compared with conventional-dose regimens in the GHSG HD9 study. 2 In a 3-armed trial, patients with stage IIB-IV HL were randomized to 8 cycles of COPP-ABVD, baseline BEACOPP (basB), or escB. Results from the most recent update of the study with 1196 evaluable patients and a median follow-up of 111 months suggest that responses are durable, with the 10-year freedom-from-treatment-failure (FFTF) significantly higher in the escB arm than in the basB and COPP-ABVD arms (82%, 70%, and 64%, respectively, P Ͻ .0001). The corresponding 10-year overall survival (OS) rates were 86%, 80%, and 75%, respectively (P ϭ .0005). 2 In contrast to the original publication, which indicated an OS benefit across all risk groups, on longer follow-up, the ...

High-Risk, Advanced-Stage Hodgkin Lymphoma: The Impact of Combined Escalated BEACOPP and ABVD Treatment in Patients Who Rapidly Achieve Metabolic Complete Remission on Interim FDG-PET/CT Scan

“…The authors concluded that an early switch from ABVD to escBEACOPP could be done safely in PET2-positive patients [14]. Currently, additional studies using similar approaches are still recruiting patients [15]. …”

“…Current ongoing prospective trials, which are still recruiting patients and employ risk-adapted strategies based on interim-PET activity [15], will probably provide new guidelines for the treatment of patients with advanced-stage HL.…”

MiR-SNPs as Markers of Toxicity and Clinical Outcome in Hodgkin Lymphoma Patients

“…Stage I–II patients are treated with chemotherapy, mainly ABVD, followed by involved field radiotherapy [5]. In stages III–IV, combination chemotherapy followed by consolidation radiotherapy in selected patients is the standard treatment, with three regimens: ABVD, escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) and STANFORD V (doxorubicin, vinblastine, mechlorethamine, vincristine, bleomycin, etoposide, and prednisone) [6]. While the majority of patients will be cured, treatment-related toxicities are often a cause of late mortality.…”

Current Approach to Allogeneic Hematopoietic Stem Cell Transplantation

“…Combination chemotherapy with or without radiation therapy results in long-term DFS and OS for about 80% of newly diagnosed patients with HL. [192] As in NHL autologous HCT is well established for the treatment of disease. [193] An approach to minimize relapse after autologous HCT for high-risk patients using the anti-CD30 antibody (brentuximab) conjugated to an anti-tubulin drug (vedotin) [SGN-35] [194] is currently being studied in a randomized phase III placebo-controlled trial as maintenance therapy following autologous HCT.…”