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Post-transplant outcomes of elderly patients with newly diagnosed AML, ineligible for induction chemotherapy, following venetoclax-based treatment

Jan 6, 2020

Allogeneic hematopoietic stem cell transplant (allo-HSCT) can be curative in patients with acute myeloid leukemia (AML). However, many older patients are not eligible for the intensive induction chemotherapy (IC) due to comorbidities or aggressive or refractory disease. Venetoclax, when combined with hypomethylating agents (HMAs), such as decitabine and azacitidine, or low dose cytarabine (LDAC), has been shown to induce durable remissions in older patients with AML who are typically considered ineligible for IC. With the availability of reduced intensity conditioning regimens before transplantations, it has been hypothesized that the use of venetoclax-based therapies in this population may allow more patients to subsequently receive allo-HSCT.1

On Saturday 7th December 2019, during the 61st American Society of Hematology (ASH) annual meeting, Keith W. Pratz, Johns Hopkins University, Baltimore, US, presented a secondary analysis of the outcomes of patients with newly diagnosed AML who are ineligible for IC, treated with venetoclax-based therapy, who subsequently underwent allo-HSCT. The study aimed to determine the impact of allo-HSCT on clinical outcome.1

Parent studies1

Two global, open-label studies evaluating the efficacy and safety of venetoclax in combination with HMAs or LDAC in patients with newly diagnosed AML, who were ineligible for IC, were used for this analysis:

  1. Phase Ib study (NCT02203773): venetoclax + HMA (decitabine or azacitidine)
  • N= 212
    • Dosing schedule:
      • Venetoclax: 400mg, 800mg, or 1200mg
      • Decitabine (intravenously [IV] on Days 1–5): 20mg/m2 or
      • Azacitidine (IV or subcutaneous [SC] on Days 1–7): 75mg/m2
  • Read more about the results of this study on the AML Global Portal here
  1. Phase I/II study (NCT02287233): venetoclax + LDAC
  • N= 92
    • Dosing schedule:
      • Venetoclax: 600mg or 800mg
      • LDAC (SC daily on Days 1–10): 20mg/m2
  • Read more about the results of this study on the AML Global Portal here

Eligible patients were aged 60 years or older, were ineligible for standard IC with cytarabine and anthracycline, had adequate renal and hepatic function, a white blood cell count ≤ 25x109/L, had not received prior therapy for AML or prior cytarabine, had intermediate or poor cytogenetics, and no known infections or active central nervous system involvement.

Patients receiving subsequent allo-HSCT1

Following treatment with venetoclax-based therapy, 10% of patients (31/304) subsequently received allo-HSCT and were evaluated for efficacy endpoints, such as best response (complete remission [CR] or CR with partial hematologic recovery [CRh]*), time to best response, time from last dose of venetoclax to allo-HSCT, and 12-month post-allo-HSCT survival. The characteristics of patients who subsequently received allo-HSCT are shown in Table 1.

* CRh is defined typically as < 5% blasts in the bone marrow, no evidence of disease, and partial recovery of peripheral blood counts (platelets > 50 × 109/L and ANC > 0.5 × 109/L). CR with incomplete hematologic recovery (CRi) is defined typically as < 5% bone marrow blasts with residual neutropenia (ANC < 1000 cells/μL) or thrombocytopenia (platelets < 100,000/μL).2

Table 1. Characteristics of patients receiving allo-HSCT (n= 31)


Patients receiving allo-HSCT

Treatment regimen, %


Venetoclax + azacitidine


Venetoclax + decitabine


Venetoclax + LDAC


Median age, years (range)

69 (63–76)

Bone marrow blasts ≥ 50%, %


Secondary AML, %


ECOG performance score (0 vs 1 vs 2), %

32 vs 35 vs 32

Cytogenetic risk (intermediate vs adverse), %

58 vs 39

Baseline mutations, %










ECOG, Eastern Cooperative Oncology Group

  • Median time on study drug: 3.7 months (range: 0.9–20)
  • Median time from last dose of venetoclax to allo-HSCT: 1.2 months (range: 0.4–10)

Twelve-month overall survival from venetoclax initiation was 84% (95% CI, 66–93) for all patients. In total, 55% (17/31) of patients were alive and in remission 12-months posttransplant, with 71% (12/17) of these patients remaining in remission for two or more years. Best responses and survival data are shown in Table 2.

Table 2. Best response to venetoclax-based treatment prior to and survival after allo-HSCT

Best response (n= 31)

Patients, %

CR/CR with CRi










Resistant disease


Median time to best response (n= 31)

Months (range)


2.3 (0.9–7.1)


2.8 (1.0–7.1)

Median survival

Months (range)

CR (n= 16)

28 (5.6–54)

CRh (n= 6)

32 (14–41)

At 12 months post-transplant

Patients, %

Alive (n= 31)


Alive and in remission (n= 31)


In remission following CR/CRi (n= 26)


In remission following CR/CRh (n= 22)


CR, complete remission; CRh, CR with partial hematologic recovery; CRi, CR with incomplete hematologic recovery; MLFS, morphologic leukemia free state


Nearly 40% of patients who received allo-HSCT following venetoclax-based therapy had durable remissions for two or more years, suggesting venetoclax-based therapy prior to allo-HSCT, even in patients who are unfit for standard induction chemotherapy, may provide a path to a curative therapy.

  1. Pratz K.W. et al., Outcomes after Stem Cell Transplant in Older Patients with Acute Myeloid Leukemia Treated with Venetoclax-Based Therapies. 2019 Dec 07. Oral Abstract #264. 61st American Society of Hematology (ASH) annual meeting and exposition, Orlando, US
  2. Bloomfield C. et al., Time to repeal and replace response criteria for acute myeloid leukemia? Blood Revs. 2018 Sep; 32(5):416–425. DOI: 10.1016/j.blre.2018.03.006

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