KEY TAKEAWAYS
- The phase 3 QuANTUM‑First Trial studied the impact of allo-HCT in CR1 + quizartinib in AML with FLT3-ITD.
- The study’s primary endpoint was OS.
- Quizartinib extended OS in CR patients, regardless of whether they had allo-HCT in CR1 or their pre-transplant MRD status.
The study aimed to assess the influence of allogeneic hematopoietic stem cell transplant (allo-HCT) during first complete remission (CR1) and its interaction with quizartinib on clinical outcomes. It also examined the correlation between pre-allo-HCT FLT3–Internal Tandem Duplication (FLT3‑ITD) measurable residual disease (MRD) levels and OS.
In the phase 3 trial, patients (pts) were assigned either quizartinib (40mg/day, administered on days 8-21) or a placebo. Those who reached complete remission (CR) or CR with incomplete hematologic recovery (CRi) underwent up to four cycles of high-dose cytarabine coupled with quizartinib (40mg/day) or a placebo, possibly followed by allo-HCT. Subsequently, they were given about three years of continuation therapy with quizartinib (30-60mg/day) or a placebo. The primary endpoint was overall survival (OS). The effect of allo-HCT during CR1 on OS was evaluated as a time-sensitive variable in multivariable regression analyses. In addition, P-values were not modified for multiplicity.
In the study, 268 pts were assigned to quizartinib and 271 to a placebo. Of these, 54.9% on quizartinib and 55.4% on placebo achieved CR, while 16.8% on quizartinib and 9.6% on placebo achieved CR with incomplete hematologic recovery (CRi) following the induction phase. Among those who reached CR, 84 pts (57.1%) on quizartinib and 73 (48.7%) on placebo went through an allo-HCT during CR1. After completing the transplant, 72.6% on quizartinib and 49.3% on placebo began a three-year continuation treatment. In addition, 115 allo-HCTs occurred outside of CR1, with 60 in the quizartinib group and 55 in the placebo group.
Multivariable analysis adjusted for FLT3-ITD variant allele frequency and gender revealed that both quizartinib (hazard ratio [HR], 0.770; 95% CI, 0.609-0.973; P=.0284) and undergoing allo-HCT in CR1 (HR, 0.424; 95% CI, 0.301-0.597; P<.0001) had a favorable impact on OS. The Simon-Makuch plot indicated that those who achieved CR with quizartinib had a longer OS compared to those on placebo, irrespective of whether they had an allo-HCT in CR1. The Kaplan-Meier plot, when focused on pts having allo-HCT in CR1 based on their latest pre-transplant FLT3-ITD MRD status (cutoff 10-4), displayed extended OS for those on quizartinib, especially for pts showing pre-allo-HCT MRD+ status.
Administering quizartinib extended OS for pts who achieved CR, regardless of whether they underwent allo-HCT during CR1. Similarly, for those who did undergo allo-HCT in CR1, the beneficial effect on OS was observed irrespective of their preallo-HCT MRD status.
Source: https://clml-soho2023.elsevierdigitaledition.com/520/index.html
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT02668653
Schlenk, R.F., Montesinos, P., Romero-Aguilar, A., Vrhovac, R., Patkowska, E., Kim, H-J., Zak, P., Wang, P-N., Hanyok, J., Liu, L., Kamel, Y.M., Lesegretain, A., Cortes, J., Sekeres, M.A., Dombret, H., Amadori, S., Wang, J., Perl, A.E., Levis, M.J., Erba, H.P. Impact of Allogeneic Hematopoietic Cell Transplantation (allo‑HCT) in First Complete Remission (CR1) in Addition to FLT3 Inhibition With Quizartinib in Acute Myeloid Leukemia (AML) With FLT3–Internal Tandem Duplication (FLT3‑ITD): Results from the QuANTUM‑First Trial.
