Improved Outcomes With Transplant After Cladribine-Based Therapy in AML

Acute myeloid leukemia (AML) cells in blood flow: © LASZLO - stock.adobe.com

The combination of cladribine, idarubicin, and cytarabine (CLIA) demonstrated efficacy with a consistent safety profile to that of other intensive regimens when used for the treatment of patients with relapsed/refractory (R/R) acute myeloid leukemia (AML), according to findings from a single-center, single-arm, phase 2 trial (NCT02115295).¹

The overall composite response rate—comprising complete remission (CR) and complete remission with incomplete hematologic recovery (CRi)—was 33%. Among patients in the salvage 1 cohort (n = 35), the CR/CRi rate was 49%. With a median follow-up duration of 61 months, the median overall survival (OS) for all patients was 7.9 months, while patients achieving CR/CRi had a median relapse-free survival (RFS) of 9.1 months. Patients in the salvage 1 cohort experienced a median OS of 12 months and a median RFS of 10.3 months.

In the subgroup treated with CLIA and sorafenib (Nexavar; n = 22), the CR/CRi rate was 41%, with a median OS of 8.8 months and a median RFS of 3.8 months. A landmark analysis showed significantly improved OS among patients who underwent transplantation compared with those who did not, with a median OS of 78 months vs 8.8 months (P <.001).

“CLIA is effective for patients with R/R AML and offers a safety profile similar to that of other intensive regimens,” study authors wrote in findings published in the American Cancer Society.

The phase 2 trial enrolled 66 patients with R/R AML.² Patients received induction with cladribine at a dose of 5 mg/m² via intravenous (IV) infusion on days 1 through 5, IV cytarabine 1000 mg/m² on days 1 through 5, and IV idarubicin 10 mg/m² on days 1 through 3. For patients with FLT3-mutated AML, sorafenib 400 mg twice daily on days 1 through 14 was added.

Enrollment was open to patients with AML, acute biphenotypic leukemia, or high-risk myelodysplastic syndrome. Patients with chronic myeloid leukemia (CML) in myeloid blast phase were also eligible for enrollment. Additional enrollment criteria required patients to have adequate organ function and an ECOG performance status of 0, 1, or 2.

For the frontline cohort, patients must have not received any prior potentially curative therapy for leukemia, but were allowed to have had previously received hydroxyurea, hematopoietic growth factors, azacitidine, decitabine, all-trans retinoic acid, or a total dose of cytarabine up to 2 g. If patients were able to receive venetoclax (Venclexta), they were assigned to frontline cohort 4. Further, patients with secondary AML who were treated for their antecedent myeloid neoplasm were enrolled into the separate secondary AML cohort.

The salvage cohort of the study included patients with previously treated, relapsed/refractory AML, acute biphenotypic leukemia, or CML in myeloid blast phase.

The primary end point was CR rate, and secondary end points were OS, overall response rate, event-free survival, duration of response, and incidence of toxicities.

Safety findings from the study showed that the 4- and 8-week mortality rates were 6% and 17%, respectively. Most grade 3 or greater adverse events were related to infection and elevated liver function tests.¹

REFERENCES:

1. Goulart H, Kantarjian H, Borthakur G, et al. Cladribine, idarubicin, and cytarabine (CLIA) for patients with relapsed and/or refractory acute myeloid leukemia: A single-center, single-arm, phase 2 trial. Cancer. 2025;131(8):e35840. doi:10.1002/cncr.35840

2. Cladribine, idarubicin, cytarabine, and venetoclax in treating patients with acute myeloid leukemia, high-risk myelodysplastic syndrome, or blastic phase chronic myeloid leukemia. ClinicalTrials.gov. Updated December 10, 2024. Accessed April 16, 2025. https://clinicaltrials.gov/study/NCT02115295