High Response Rate With Venetoclax Plus Cladribine, Idarubicin, and Cytarabine 

In a phase 2 trial, combination venetoclax, cladribine, idarubicin, and cytarabine led to a high rate of minimal residual disease (MRD)-negative remission in younger patients with newly diagnosed AML.4 

Previous results from this trial (ClinicalTrials.gov Identifier: NCT02115295) were considered encouraging.7 At ASH 2022, Patrick K. Reville, MD, of The University of Texas MD Anderson Cancer Center in Houston, presented updated results.4 

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Dr Reville presented results in 67 patients — 60 with AML, 4 with high-risk myelodysplastic syndrome, and 3 with mixed phenotype acute leukemia. The median age at baseline was 48 years (range, 18-64).

For induction, patients received cladribine at 5 mg/m2 on days 1-5, cytarabine at 1500 mg/m2 (1000 mg/m2 for patients ≥ 60 years) on days 1-5, and idarubicin at 10 mg/m2 on days 1-3. Venetoclax was administered at 400 mg without ramp-up on days 2-8 of each cycle, with dose modification for patients on CYP3A4 inhibitors. 

Consolidation therapy consisted of cladribine at 5 mg/m2 on days 1-3, idarubicin at 8 mg/m2 on days 1-2, and cytarabine at 1000 mg/m2 (750 mg/m2 for patients ≥ 60 years) on days 1-3. Venetoclax was administered at 400 mg on days 2-8.

The composite complete response rate (CRc; CR plus CRi) was 96%, and 85% of patients achieved a CR. Two patients did not have a response. One patient died in the first 4 weeks, and 2 died within 8 weeks.

Among 61 evaluable patients, 77% were MRD negative at the first response assessment, and 90% were MRD negative at any point on study. Among responders, 70% went on to receive allo-HSCT. 

The median follow-up was 25.3 months. The median duration of response, median event-free survival (EFS), and median OS were not reached. The 12-month EFS rate was 70%, and the 24-month EFS rate was 68%. The 12-month OS rate was 86%, and the 24-month OS rate was 71%. 

When patients were divided by European Leukemia Network risk groups, the median EFS and OS were exactly the same. The median EFS and OS were not reached in the favorable-risk group, were 31.7 months in the intermediate-risk group, and were not reached in the adverse-risk group. 

The most common AEs were febrile neutropenia (78%), ALT elevation (76%), fatigue (58%), skin rash (34%), bacteremia (34%), and nausea (31%). There were 4 fatal AEs — gram-positive bacteremia, gram-negative bacteremia, fungal sinusitis, and rhinovirus pneumonia.

“This study is important given that it is showing a new combination of upfront intensive chemotherapy with inclusion of venetoclax with encouraging response rates and tolerability,” said Hetty Carraway, MD, of the Cleveland Clinic Taussig Cancer Center in Ohio, who was not involved in this study.

“AML induction regimens are moving away from intensification of cytotoxic chemotherapy, so this is somewhat of a throwback approach,” said Dr Levis, who was not involved in the study. “I suspect this regimen will end up being most commonly used as a salvage regimen rather than emerging as a standard of care for newly diagnosed AML.”

Disclosures: The pivekimab triplet study was sponsored by ImmunoGen, Inc. and Jazz Pharmaceuticals. Click the following links to see disclosures for Dr Mascarenhas, Dr Levis, Dr Gerds, and Dr Carraway. Dr Abdul Hay disclosed relationships with Kite Pharma, Daiichi Sankyo, Rigel Pharmaceuticals, Jazz Pharmaceuticals, Servier, and Takeda. Dr Choi reported having no disclosures. Some of the study presenters and their colleagues declared affiliations with various companies. Please see the references below for a full list of their disclosures.  


1. Stelljes M, Middeke JM, Bug G, et al. In patients with relapsed/refractory AML sequential conditioning and immediate allogeneic stem cell transplantation (allo-HCT) results in similar overall and leukemia-free survival compared to intensive remission induction chemotherapy followed by allo-HCT: Results from the randomized phase III ASAP trial.  Presented at ASH 2022. December 10-13, 2022. Abstract 4.

2. Röllig C, Steffen B, Schliemann C, et al. Single versus double induction with “7+3” containing 60 versus 90 mg daunorubicin for newly diagnosed AML: Results from the randomized controlled SAL Dauno-Double Trial. Presented at ASH 2022. December 10-13, 2022. Abstract 217. 

3. Daver N, Montesinos P, Aribi A, et al. Broad activity for the pivekimab sunirine (PVEK, IMGN632), azacitidine, and venetoclax triplet in high-risk patients with relapsed/refractory acute myeloid leukemia (AML). Presented at ASH 2022. December 10-13, 2022. Abstract 62. 

4. Reville PK, Kantarjian H, Borthakur G, et al. Venetoclax combined with cladribine, idarubicin, cytarabine (CLIA) as induction therapy in patients with newly diagnosed acute myeloid leukemia and high-risk myelodysplastic syndrome. Presented at ASH 2022. December 10-13, 2022. Abstract 709.

5. Luskin MR, Lee J-W, Fernandez HF, et al. Benefit of high-dose daunorubicin in AML induction extends across cytogenetic and molecular groups. Blood. 2016;127(12):1551-1558. doi:10.1182/blood-2015-07-657403

6. Stone RM, Mandrekar SJ, Sanford BL, et al. Midostaurin plus chemotherapy for acute myeloid leukemia with a FLT3 mutation. N Engl J Med. 2017;377(5):454-464. doi:10.1056/NEJMoa1614359

7. Kadia TM, Reville PK, Borthakur G, et al. Venetoclax plus intensive chemotherapy with cladribine, idarubicin, and cytarabine in patients with newly diagnosed acute myeloid leukaemia or high-risk myelodysplastic syndrome: A cohort from a single-centre, single-arm, phase 2 trial. Lancet Haematol. 2021;8(8):e552-e561. doi:10.1016/S2352-3026(21)00192-7