Clinical Outcomes and Characteristics of Patients (pts) with FLT3–Internal Tandem Duplication (FLT3-ITD)–Mutated Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML) Undergoing Hematopoietic Stem Cell Transplant (HSCT) after Quizartinib (Q) or Salvage Chemotherapy (SC) in the Quantum-R Trial

Abstract

<h3>Introduction</h3> In QuANTUM-R, the once-daily, oral, highly potent and selective FLT3 inhibitor Q improved clinical benefit vs SC (median overall survival [mOS], 6.2 vs 4.7 mo [HR, 0.76 (95% CI, 0.58-0.98); <i>P</i> = .02]) in R/R <i>FLT3</i>-ITD AML (NCT02039726). Before randomization, 25% (Q) and 23% (SC) of pts had 1 prior HSCT. <h3>Objective</h3> To describe post hoc analyses in pts who underwent subsequent HSCT during QuANTUM-R. <h3>Methods</h3> Pts with <i>FLT3</i>-ITD R/R AML received Q (60 mg [30-mg lead-in]) or SC. Pts in the Q arm could resume Q 30-100 d after HSCT. Decisions to proceed to HSCT and resume Q after HSCT were made per investigator discretion/institutional policy. <h3>Results</h3> Of 367 randomized pts, 85 in the Q arm underwent any subsequent HSCT (allogeneic HSCT [allo-HSCT], 84 [6 with and 78 w/o additional AML therapy]; autologous HSCT, 1), and 19 in the SC arm underwent any HSCT (5 with and 14 w/o additional AML therapy]). Q + SC pooled data showed a longer mOS (95% CI) in 104 pts with any HSCT vs 263 w/o (12.2 [10.0-24.1] vs 4.4 [4.1-4.9] mo; <i>P</i> < .0001; Fig 1); 1-year OS rates were 50% vs 13%. Among pts preselected for low-intensity therapy, 13/57 in the Q arm and 0/29 in the SC arm underwent any HSCT. Q + SC pooled data also showed a longer mOS (95% CI) in pts with a composite complete remission (CRc) as last recorded response before allo-HSCT vs pts w/o CRc (20.1 [11.7-NA] vs 8.8 [7.0-11.4] mo). Regardless of treatment, mOS was longer with any HSCT vs w/o (Q, 11.9 [10.2-25.1] vs 4.5 [4.1-5.4] mo; SC, 12.7 [6.1-NA] vs 4.0 [2.7-5.0] mo); respective 1-year OS rates were 50% vs 13% and 51% vs 12%. In the Q arm, mOS (95% CI) was longer in pts with a best response of CRc who resumed Q after allo-HSCT (27.1 [18.2-NA] mo) vs pts not resuming Q (5.4 [4.7-11.4] mo; Fig 2). In 48 pts (62%) in the Q arm resuming Q after allo-HSCT, median time from allo-HSCT to Q resumption was 65 d (range, 30-106 d). Four pts (5%) in the Q arm died < 30 d after allo-HSCT. As of 2/22/2018, 46/78 pts in the Q arm (59%) and 9/14 pts in the SC arm (64%) with allo-HSCT w/o additional AML therapy died, mostly due to AML progression (Q, 31 [40%]; SC, 7 [50%]). The frequency of treatment-emergent adverse events (TEAEs) and TEAEs of interest was similar in pts resuming Q after allo-HSCT and in the overall Q population. <h3>Conclusion</h3> Independent of HSCT, Q improved survival vs SC in pts with <i>FLT3</i>-ITD R/R AML in QuANTUM-R. Q + SC pooled analyses showed longer survival in pts with HSCT vs pts w/o and in pts with CRc before allo-HSCT. Survival in transplanted pts was similar in both arms, indicating that HSCT-eligible pts received transplants appropriately, and the higher HSCT rate in the Q arm was beneficial. In pts preselected for low-intensity SC at study entry, 13 were able to undergo HSCT after Q treatment. Q resumption after HSCT was associated with better survival outcomes and was tolerable. These data illustrate the value of using Q to target the <i>FLT3</i>-ITD mutation as a part of the overall treatment sequence in pts with <i>FLT3</i>-ITD R/R AML.