The use of venetoclax‐based salvage therapy for post‐hematopoietic cell transplantation relapse of acute myeloid leukemia

Abstract

For patients with high risk myeloid disease, allogeneic hematopoietic cell transplantation (HCT) is the only potentially curative therapy. Unfortunately, many of these patients relapse after HCT and have a limited survival. The recent approval of venetoclax, an orally bioavailable BCL‐2 inhibitor, resulted in significant responses in treatment naïve acute myeloid leukemia (AML), and off‐label use in the relapsed/refractory setting is increasing. We report the outcomes of 21 patients who underwent allogeneic HCT for myeloid disease, relapsed with AML, and were treated with venetoclax. Several patients had poor risk features including antecedent hematologic malignancy (6/21), complex karyotype (6/21), and TP53 mutations (5/21). The median age was 64.5 years and time from HCT to relapse was 5.7 months (range: 0.9 to 44.9 months). Of the 19 patients who were assessed for response, there were meaningful treatment responses seen in eight patients: five CR, three CRi, zero PR, for an ORR of 42.1%. Treatment effect was seen in six additional patients, including four in the morphologic leukemia‐free state. Nine patients maintained their response for ≥3 months and eight were receiving therapy at data cut. Post‐HCT AML relapse has an exceedingly poor outcome, and venetoclax‐based therapy is a potent therapy option that should be studied prospectively in this setting.

Prediction of Response and Survival Following Treatment with Azacitidine for Relapse of Acute Myeloid Leukemia and Myelodysplastic Syndromes after Allogeneic Hematopoietic Stem Cell Transplantation

“…Aiming to support physicians in this decision making process in the future, we developed a practical score for the entire cohort, which comprises the two variables type of relapse and time to relapse based on their weights in multivariate analysis. This score clearly separated patients into 3 groups with different outcomes: patients in groups 1 and 2, e.g., those with late molecular relapse who had promising CR and 2-year OS rates of 71% and 64%, respectively; patients in group 3 with early hematologic relapse exhibited CR and 2-year OS rates of 29% and 27%, suggesting that in these patients alternative strategies such as addition of a second compound (i.e., Lenalidomide [ 31 , 32 ], Venetoclax [ 33 ]) or investigational agents might improve their prognosis. Furthermore, the currently available FLT3 inhibitors such as Gilteritinib or Sorafenib may represent alternatives, either alone or in combination with Aza, for patients with FLT3 mutation at relapse, which was the case in 11 of 38 of our patients tested at relapse [ 25 , 34 , 35 ].…”

Venetoclax-based chemotherapy in acute and chronic myeloid neoplasms: literature survey and practice points

“…Since approval of venetoclax in 2018 for upfront use in AML, it has gained popularity as a salvage regimen with a handful of published retrospective reports that are delineated in Table 2 (refs. 20,[25][26][27][28][29][30][31][32][33][34] ). We recommend exercising caution while interpreting findings from these reports due to immense heterogeneity in patient population studied (inclusion of relapsed MDS, other myeloid malignancies, prior HMA exposure, post AHSCT), in addition to variations in dose and schedule of treatment regimens utilized either as monotherapy, combination with HMA or low-dose cytarabine.…”

“…In regard to venetoclax use as salvage therapy in post AHSCT patients, a recent review of 21 patients solely focused on relapsed AML following transplant performed for either AML (n = 16) or chronic myeloid malignancy (n = 2, MDS, n = 1 each with chronic myelomonocytic leukemia (CMML) and primary myelofibrosis) 32 . The majority of patients received venetoclax with HMA (n = 16).…”

Recent advances of targeted therapy in relapsed/refractory acute myeloid leukemia

“…Of the 19 patients who were assessed for response, VEN yielded an ORR of 42.1%. About 47.4% patients maintained their response for ≥3 months and 8 patients were still receiving therapy at time cut [ 71 ]. The objective response rate of VEN-based combination therapy was raging from 20% to 70% in R/R AML patients.…”