Phase II Study of Venetoclax Added to Cladribine Plus Low-Dose Cytarabine Alternating With 5-Azacitidine in Older Patients With Newly Diagnosed Acute Myeloid Leukemia

Author(s): Tapan M. Kadia, MD1; Patrick K. Reville, MPH, MD2; Xuemei Wang, MS3; Caitlin R. Rausch, PharmD4; Gautam Borthakur, MD1; Naveen Pemmaraju, MD1; Naval G. Daver, MD1; Courtney D. DiNardo, MD, MSCE1; Koji Sasaki, MD, PhD1; Ghayas C. Issa, MD1; Maro Ohanian, MD1; Guillermo Montalban-Bravo, MD1; Nicholas J. Short, MD1; Nitin Jain, MD1; Alessandra Ferrajoli, MD1; Kapil N. Bhalla, MD1; Elias Jabbour, MD1; Koichi Takahashi, MD, PhD1; Rashmi Malla, BSN1; Kelly Quagliato, BS1; Rashmi Kanagal-Shamanna, MD5; Uday R. Popat, MD6; Michael Andreeff, MD, PhD1; Guillermo Garcia-Manero, MD1; Marina Y. Konopleva, MD, PhD1; Farhad Ravandi, MD1; and Hagop M. Kantarjian, MD1
Source: DOI: 10.1200/JCO.21.02823 Journal of Clinical Oncology 40, no. 33 (November 20, 2022) 3848-3857.
Anjan J Patel MD

Dr. Anjan Patel's Thoughts

This seems like a potential future option for older/unfit patients with AML.  Small study of 60 patients, treatment was CLAD 5mg/m2 D1-5 + sub-cut LDAC 20mg BID + venetoclax 400mg D1-21.  Response rates were very high with CR of 93% and MRD-neg in 84% of patients.

PURPOSE

The combination of venetoclax and 5-azacitidine (5-AZA) for older or unfit patients with acute myeloid leukemia (AML) improves remission rates and survival compared with 5-AZA alone. We hypothesized that the addition of venetoclax to cladribine (CLAD)/low-dose araC (low-dose cytarabine [LDAC]) alternating with 5-AZA backbone may further improve outcomes for older patients with newly diagnosed AML.

METHODS

This is a phase II study investigating the combination of venetoclax and CLAD/LDAC alternating with venetoclax and 5-AZA in older (≥ 60 years) or unfit patients with newly diagnosed AML. The primary objective was composite complete response (CR) rate (CR plus CR with incomplete blood count recovery); secondary end points were overall survival, disease-free survival (DFS), overall response rate, and toxicity.

RESULTS

A total of 60 patients were treated; median age was 68 years (range, 57-84 years). By European LeukemiaNet, 23%, 33%, and 43% were favorable, intermediate, and adverse risk, respectively. Fifty-six of 60 evaluable patients responded (composite CR: 93%) and 84% were negative for measurable residual disease. There was one death (2%) within 4 weeks. With a median follow-up of 22.1 months, the median overall survival and DFS have not yet been reached. The most frequent grade 3/4 nonhematologic adverse events were febrile neutropenia (n = 33) and pneumonia (n = 14). One patient developed grade 4 tumor lysis syndrome.

CONCLUSION

Venetoclax and CLAD/LDAC alternating with venetoclax and 5-AZA is an effective regimen among older or unfit patients with newly diagnosed AML. The rates of overall survival and DFS are encouraging. Further study of this non–anthracycline-containing backbone in younger patients, unfit for intensive chemotherapy, as well as comparisons to standard frontline therapies is warranted.

Author Affiliations

1Departments of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX; 2Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX; 3Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX; 4Department of Pharmacy, The University of Texas MD Anderson Cancer Center, Houston, TX; 5Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX; 6Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX

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