Safety and Efficacy of Pomalidomide and Azacitidine Combination in MRD-Guided Preemptive Treatment of Acute Leukemia after Allogeneic Stem Cell Transplantation
Authors: Wang Lu , Liu Jia , Zhu Lidan , Liu Huanfeng , Gao Shichun , Kong Peiyan , Zhang Xi , Gao Lei 
Published: December 2024

Background: Previous studies have shown that the combination of azacitidine and lenalidomide is effective in some patients with recurrent AML and MDS after allogeneic stem cell transplantation. And our published study have confirmed the good safety profile of this combination for post-allograft AML maintenance therapy. Pomalidomide is a new immunomodulatory agent which has been shown to be effective in patients with steroid resistant and refractory chronic GVHD. Therefore, we hypothesized that it may separate GVL effect and GVHD, and tried to use the combination of it and azacitidine as MRD-guided preemptive treatment of acute leukemia. Objective: To analyze the safety and efficacy of pomadidomide and azacitidine combination in MRD-guided preemptive treatment of acute leukemia after allogeneic stem cell transplantation. Methods: Azacitidine 75 mg/m2 was subcutaneously administered on days 1-5, and pomalidomide 1 mg per day was orally taken on days 1-28 of a 28-day cycle. Results: Eight patients diagnosed with acute myeloid leukemia, 1 patient diagnosed with acute mixed lineage leukemia, 2 patients diagnosed with Ph+ ALL, 2 patients diagnosed with Ph- ALL and 1 patient diagnosed with T-ALL received protocol treatment as MRD-guided preemptive treatment. During a median follow-up period of 575 days (range 42-1184), 8 patients developed grade 3-4 neutropenia, but no patient had febrile neutropenia. One patients developed grade 4 thrombocytopenia. Grade 3-4 aminotransferase elevation occurred in 3 patients. Severe adverse event, manifesting as ketoacidosis was observed in 1 patient, but it was not likely to be associated with protocol treatment. No patient developed acute GVHD after treatment initiation. One patient developed mild new-onset chronic skin GVHD during treatment with an NIH score of 1, but he discontinued calcineurin inhibitor at the start of treatment. In 6 patients had chronic GVHD before the initiation of protocol treatment only 1 experienced an exacerbation of chronic GVHD. In the patients diagnosed with acute myeloid leukemia and acute mixed lineage leukemia, one relapsed after a 368-day follow-up, one was lost to follow-up after 42 days with her MRD remaining positive and the remaining patients were in relapse-free survival after a follow-up period of 399 to 1184 days. Of the two patients with Ph+ ALL, one had an intermittently positive BCR / ABL fusion gene and eventually relapsed after a 462-day follow-up, the other was in BCR /ABL fusion gene-negative remission after a 770-day follow-up. The patient diagnosed with T-ALL relapsed and received other treatment after a 70-day follow-up. The two patients with Ph- ALL remained in MRD-negative remission after a 315-day and 527-day follow-up, respectively. Conclusions: The current data indicate that pomalidomide and azacitidine combination is well tolerated in acute leukemia patients and can induce a good response in AML patients with positive MRD after allogeneic hematopoietic stem cell transplantation. We have registered a trial to further explore the safety and efficacy of the combination in MRD-guided preemptive treatment of AML after allogeneic hematopoietic stem cell transplantation (ChiCTR2300075432).