Addition of Cladribine: Improving Standard of Care in Newly Diagnosed Acute Myeloid Leukemia
Authors: Mori Shahram , Rivera Nahir , Wazir Mohammed , Patel Rushang D. , Varela Juan Carlos , Zhu Xiang , Balls Jason , Smith Tori , Goldstein Steven C. 
Published: October 2019

Abstract
Acute myeloid leukemia (AML) continues to be one of the most common myeloid malignancies in the United States. Achieving a complete response (CR) after induction with standard daunorubicin and cytarabine (7+3) remains suboptimal, occurring in 55-65% of patients. No significant advances have improved these outcomes in the last decade. A recent phase III randomized clinical trial by the Polish Adult Leukemia Group (PALG), showed that adding cladribine 5mg/m2 to standard 7+3 (Daunorubicin 60mg/m2, Ara-C 200mg/m2) improved CR rates to 68% vs 56% with standard 7+3 alone. Achieving a higher CR is important in the outcome of high-risk patients who require allogeneic stem cell transplantation (Allo-SCT) as a curative measure. At our center, we conducted a retrospective analysis evaluating the addition of cladribine to the current standard of care treatment in newly diagnosed AML. We hypothesized an improvement in CR rates in all-risk patients will allow more patients to proceed to Allo-SCT.
Adult patients 18 years of age or older with newly diagnosed AML who received remission induction chemotherapy between May 2012 and May 2018 were included in the study. A total of 118 AML patients were screened and those who did not complete induction or did not have bone marrow biopsy at end of induction chemotherapy were excluded. A total of 100 patients were evaluable of which 26 (26%) received DAC and 74 (74%) received 7+3. Within the 7+3 group, 29 (39%) received a Daunorubicin dose of 60mg/m2 (D60) and 45 (61%) received a dose of 90mg/m2 (D90). A higher absolute CR rate was noted after one induction in the DAC group as compared to the combined 7+3 group (21 [80.7%] vs. 49 [66.2%], respectively). The improvement in CR between DAC and D60 reached statistical significance (p=0.043) but there was no statistically significance difference in CR rates between DAC vs D90 (p=0.48). It is interesting to note that more patients in D60 (39%) and D90 (26%) group required re-induction as compared with DAC (12%) (p=0.067). Median overall survival (OS) for the DAC group was not reached, while median OS for D60 was 10 (DAC vs D60 p=0.076) and for D90 was 28 months (DAC vs D90 p=0.97). In the subgroup of patients who underwent Allo-SCT, median OS in the D90 group was 30 months (DAC vs D90 p=0.43) while not reached in the DAC and D60 group (DAC vs D60 p=0.84). For all patients, the median relapse-free survival (RFS) for the DAC cohort was not reached. Median RFS was 12 months for D60 (DAC vs D60 p=0.047) and 25 months for D90 (DAC vs D90 p=0.166) groups. There was no difference in OS and RFS between all three groups who were transplanted in first CR (CR1).
In conclusion CR rates following induction chemotherapy were higher in DAC vs Daunorubicin groups, however only statistically significant with respect to D60. Additionally a statistically significant improvement in RFS and a trend towards improved OS was noted in favour of DAC vs D60. Regardless of the induction chemotherapy, there was no difference in OS and RFS of patients who were transplanted in CR1. These results have encouraged us to perform a prospective comparison of standard 7+3 with Dauno 90mg/m2 and DAC.

Disclosures
No relevant conflicts of interest to declare.