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.

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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