Principles of chemotherapy in hodgkin lymphoma

Abstract

Hodgkin lymphoma (HL) is one of the first malignancies that was curable using combination chemotherapy. The principles of combination chemotherapy used in treating many malignancies were developed for the treatment of HL. The concept of combination chemotherapy, originally developed for childhood acute lymphoblastic leukemia, was applied to advanced-stage HL by DeVita and colleagues at the US National Cancer Institute when they developed the MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) regimen. The ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) regimen was developed by Bonadonna and colleagues at the Milan Tumor Institute. Trials using combinations of the two regimens, either alternated monthly or in hybrid form, improved progression-free survival (PFS), although not overall survival (OS), as compared with MOPP alone. Further trials showed that this PFS advantage was attributable to ABVD alone rather than to the combination, which led to the establishment of ABVD as a standard regimen. Further improvement in PFS was demonstrated using the more intensive escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) regimen, although it had higher toxicity. The combination of the antibody-drug conjugate brentuximab vedotin with AVD improved short-term PFS as compared with ABVD. Chemotherapy regimens such as ABVD in combination with radiation therapy improved PFS, although not OS, in several clinical trials for early-stage HL patients. More recently, chemotherapy alone provided excellent results in this population. Interim positron emission tomography/computed tomography (PET/CT) response as a biomarker during chemotherapy has been used to tailor therapy in recent clinical trials. High-dose chemotherapy with autologous stem cell support is still employed as a potentially curative second-line treatment. New effective immune therapies are also under investigation in combination with or substituting for chemotherapy. The objective of current research is to maintain or improve excellent treatment results while minimizing treatment risks.