ASH 2024 | The addition of pegfilgrastim to reduce the toxicity of CLIA plus venetoclax in patients with AML

In the Phase II CLIA venetoclax trial, we explored the safety and efficacy of pegfilgrastim, which is a sustained duration form of granulocyte colony stimulating factor or G-CSF in patients with AML treated with novel intensive chemotherapy regimens. In the CLIA venetoclax trial, we saw exceptional rates of response and overall survival in AML. This data was presented in a separate oral presentation. In 89 patients with AML, the composite complete remission rate was 94%, and the estimated five-year overall survival was 73%. However, the regimen produces profound cytopenias, which predisposes to more frequent infections, so we looked at ways to reduce toxicity. The CLIA-venetoclax trial started enrolling patients in 2019. At the time, we did not have G-CSF built into the regimen. So in 2022, we integrated pegfilgrastim into the CLIA-venetoclax protocol. We gave cladribine 5 mg per m2 for 5 days, idarubicin 8-10 mg per m2 for 3 days, cytarabine 1-1.5 g per m2 for 5 days, and venetoclax for 7 days. And in 2022, we built pegfilgrastim into the regimen at a dose of 6 milligrams once on day 6. So in this study, we analyzed 36 patients who received CLIA-venetoclax with pegfilgrastim and 53 patients who received CLIA-venetoclax without pegfilgrastim. And there were no significant differences in the baseline characteristics between cohorts, except that patients treated without pegfilgrastim had a higher proportion of AML with FLT3 ITD and received a FLT3-directed tyrosine kinase inhibitor. We found that pegfilgrastim significantly improves the median time to complete count recovery. Patients treated without G-CSF had complete count recovery in 30 days compared to 24.5 days with pegfilgrastim. Additionally, pegfilgrastim significantly reduced the incidence of neutropenic fever from 88% to 61% and bacteremia from 36% to 8%. Patients treated with pegfilgrastim had significantly higher absolute neutrophil counts at the time of count recovery. We did not observe any difference in response or MRD negativity in patients treated with CLIA-venetoclax with and without pegfilgrastim. We also did not observe any significant differences in overall survival, event-free survival, or the cumulative incidence of relapse, although all three tended to non-significantly favor pegfilgrastim use. Additionally, pegfilgrastim was associated with a non-significant decrease in infection-related deaths. Therefore, pegfilgrastim improves the time to count recovery by 5.5 days and significantly reduces the incidence of infectious-related complications. It has no impact on the rates of AML relapse, and as of today, pegfilgrastim remains integrated into the CLIA-venetoclax protocol.

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