BRENTUXIMAB VEDOTIN AS A BRIDGE TO TRANSPLANT IN HODGKIN LYMPHOMA PATIENTS. EXPERIENCE FROM TREATED PATIENTS IN NORTH MACEDONIA

Olivera Gjeorgjieva Janev; Blagica Pecanova Dungevska; Tara Mojsovska Ristevska; Merve Purde; Andrea Paunoska; Zlate Stojanoski; Irena Dimitrovska; Marica Pavkovikj; Slobodanka Trpkovska Terzieva; Tatjana Sotirova; Marija Popova Labachevska; Lazar Chadievski; Aleksandra Pivkova Veljanovska; Sonja Genadieva Stavrikj

Olivera Gjeorgjieva Janev University Clinic of Hematology Skopje, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, North Macedonia
Blagica Pecanova Dungevska General Hospital Strumica, North Macedonia
Tara Mojsovska Ristevska
Merve Purde University Clinic of Hematology Skopje, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, North Macedonia
Andrea Paunoska University Clinic of Hematology Skopje, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, North Macedonia
Zlate Stojanoski University Clinic of Hematology Skopje, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, North Macedonia
Irena Dimitrovska University Clinic of Toxicology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, North Macedonia
Marica Pavkovikj University Clinic of Hematology Skopje, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, North Macedonia
Slobodanka Trpkovska Terzieva University Clinic of Hematology Skopje, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, North Macedonia
Tatjana Sotirova University Clinic of Hematology Skopje, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, North Macedonia
Marija Popova Labachevska University Clinic of Hematology Skopje, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, North Macedonia
Lazar Chadievski University Clinic of Hematology Skopje, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, North Macedonia
Aleksandra Pivkova Veljanovska University Clinic of Hematology Skopje, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, North Macedonia
Sonja Genadieva Stavrikj University Clinic of Hematology Skopje, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, North Macedonia

Abstract

The treatment of Hodgkin lymphoma (HL) has evolved significantly since the discovery of monoclonal antibodies (mAbs), which have been promising in improving outcomes, particularly in relapsed/refractory cases. Brentuximab vedotin (BV), an antibody-drug conjugate (ADC) targeting the CD30 antigen, has emerged as an effective treatment for HL, demonstrating improved survival outcomes in patients who have failed conventional chemotherapy regimens. Objective: This study aims to evaluate the efficacy and clinical outcomes of BV-based salvage therapy followed by autologous stem cell transplantation (auto-PBSCT) in patients with relapsed or refractory Hodgkin lymphoma (R/R HL) in North Macedonia. Methods: A retrospective analysis was conducted involving 47 patients treated with BV at the Clinic of Hematology in Skopje starting from the drug's approval in December 2022 to the latest review of patient histories in December 2024. The study primarily focused on patients initially treated with the ABVD regimen, followed by BV-based salvage therapy and subsequent auto-PBSCT. Results: Out of the 47 patients, 53% were male and 47% were female, with a median age of 36 at diagnosis. The most common histopathological subtype was nodular sclerosis HL (60%), consistent with national data. Most patients (87%) received the ABVD regimen as initial treatment. In 5 patients (10.6%) a subsequent second-line salvage BV-DHAP therapy with following auto-PBSCT was applied, and in these patients, no detectable PET/CT progression was observed and the treatment was continued with a BV maintenance therapy. In 12 patients (25.5%), BV-DHAP was used as a second-line therapy, with failure to achieve remission, which was the reason to switch the regimen to BEGEV followed by auto-PBSCT in three of the patients, whereas the rest of the patients were treated with augmented ICE, BV-ICE or escalated to the escalated BEACOPP regimen. Most of these patients are currently being administered a maintenance therapy with BV or Nivolumab. Only one of the patients that was given an augmented ICE protocol had a fatal outcome due to refractoriness of the disease. In 9 patients (19%), the escalated BEACOPP protocol was used as a second-line therapeutic regimen. All of them achieved clinical remission and afterwards were subjected to salvage therapy with BV-DHAP/BV-BEGEV and subsequent auto-PBSCT. The treatment outcomes, including progression-free survival (PFS), are consistent with global studies demonstrating the benefit of BV in R/R cases of HL. Conclusion: BV-based salvage therapy followed by auto-PBSCT is an effective treatment strategy for R/R HL, with promising outcomes in patients who fail ABVD. Our findings support the growing evidence for BV as a key component in the treatment of R/R HL, particularly in the case of high-risk patients. Further studies are needed to explore optimal dosing regimens and long-term survival outcomes.

Keywords: brentuximab vedotin, CD30, CD30 targeting.

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