Treatment of myeloid malignancies relapsing after allogeneic hematopoietic stem cell transplantation with venetoclax and hypomethylating agents—a retrospective multicenter analysis on behalf of the German Cooperative Transplant Study Group
Esther Schuler, Eva‐Maria Wagner‐Drouet, Salem Ajib, Gesine Bug, Martina Crysandt, Sabine Dressler, Andreas Hausmann, Daniela Heidenreich, Klaus Hirschbühl, Matthias Hoepting, Edgar Jost, Jennifer Kaivers, Stefan Klein, Michael Koldehoff, Lambros Kordelas, Oliver Kriege, Lutz Müller, Christina Rautenberg, Judith Schaffrath, Christoph Schmid, Daniel Wolff, Rainer Haas, Martin Bornhäuser, Thomas Schroeder, Guido Kobbe, On behalf of the German Cooperative Transplant Study Group
Abstract
Abstract Treatment of relapse after allogeneic hematopoietic stem cell transplantation (alloHSCT) remains a great challenge. Aiming to evaluate the combination of venetoclax and hypomethylating agents (HMAClax) for the treatment of relapse of myeloid malignancies after alloHSCT, we retrospectively collected data from 32 patients treated at 11 German centers. Venetoclax was applied with azacitidine ( n = 13) or decitabine ( n = 19); 11 patients received DLI in addition. HMAClax was the first salvage therapy in 8 patients. The median number of cycles per patient was 2 (1–19). All but 1 patient had grade 3/4 neutropenia. Hospital admission for grade 3/4 infections was necessary in 23 patients (72%); 5 of these were fatal. In 30 evaluable patients, overall response rate (ORR) was 47% (14/30, 3 CR MRD neg , 5 CR, 2 CRi, 1 MLFS, 3 PR). ORR was 86% in first salvage patients versus 35% in later salvage patients ( p = 0.03). In 6 patients with molecular relapse (MR), ORR was 67% versus 42% in patients with hematological relapse (HR) ( n = 24, p = n.s.). After a median follow-up of 8.4 months, 25 patients (78%) had died and 7 were alive. Estimated median overall survival was 3.7 months. Median survival of patients with HMAClax for first versus later salvage therapy was 5.7 and 3.4 months ( p = n.s.) and for patients with MR (not reached) compared to HR (3.4 months, p = 0.024). This retrospective case series shows that venetoclax is utilized in various different combinations, schedules, and doses. Toxicity is substantial and patients who receive venetoclax/HMA combinations for MR or as first salvage therapy derive the greatest benefit.