Summary of TCT 2020 highlights – part 2: Transplant outcomes in patients with adverse risk AML

This article is based on an overview of the International Academy for Clinical Hematology webinar delivered by Bipin Savani on April 1, 2020. It is the second part of a series summarizing the highlights from the Transplantation & Cellular Therapy (TCT) 2020 meeting.

Abstract 7: Clinical outcomes and characteristics of patients with FLT3-ITD mutated relapsed/refractory (R/R) AML undergoing HSCT after quizartinib or salvage chemotherapy in the QuANTUM-R trial¹

The authors assessed whether improved complete response (CR) with quizartinib would result in an increased number of patients eligible for allogeneic-hematopoietic stem cell transplantation (allo-HSCT).

Previous results from the phase III QuANTUM-R study (NCT02039726) demonstrated clinical benefit of quizartinib, a selective FLT3 inhibitor over salvage chemotherapy in patients with FLT3-ITD relapsed/refractory (R/R) acute myeloid leukemia (AML). The abstract presented results of post hoc analysis of clinical outcomes in patients who underwent subsequent HSCT. Read about study methods and previous results here.

In total, 85 of 245 patients treated with quizartinib and 19 of 122 patients in the salvage chemotherapy group underwent HSCT. Forty nine patients in the quizartinib arm were continued on the drug after transplantation.

Efficacy

• There were no significant differences in survival after allo-HSCT between treatment arms
• Overall survival (OS) r by transplant status is presented in Table 1

Table 1. A pooled analysis of survival after quizartinib and salvage therapy by transplant status

allo-HSCT, allogeneic-hematopoietic stem cell transplantation; CI, confidence intervals; OS, overall survival
	Allo-HSCT (n= 92)	No HSCT (n= 263)
Median OS (95% CI), months	12.2 (9.9–25.1)	4.4 (4.1–4.9)
1-year OS rate (95% CI), %	50 (39–60)	13 (9–18)
2-year OS rate (95% CI), %	39 (29–50)	7 (3–011)

Conclusion

Transplantation rates were higher among patients with FLT3-ITD R/R AML who received quizartinib than those on salvage chemotherapy (32% vs 11%), suggesting enhanced rates of CR rates and reduction of prior-transplant mortality. The results suggest that continuation of quizartinib after allo-HSCT improves survival. However, additional studies are needed to validate these results.

Abstract 8: Allogeneic stem cell transplantation for AML patients with RUNX1 mutation in first complete remission: A study on behalf of the ALWP of the EBMT²

RUNX1 mutations in AML are associated with poor outcomes due to higher rates of chemotherapy resistance and is considered an adverse risk factor according to the European Leukemia Net classification. While there is sufficient evidence to show the negative impact of RUNX1 mutations on outcome after allo-HSCT in patients with myelodysplastic syndromes (MDS) and secondary AML, its impact on outcome after allo-HSCT in patients with de novo AML has not been established.

To address that, the Acute Leukemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT) conducted a retrospective registry analysis. Data from adult patients undergoing allo-HSCT between the years 2013 and 2018 for AML in first CR, with matched related/unrelated donor were included in the study.

Patient characteristics

• In total, across 101 European centers, data from 515 patients, including 128 with RUNX1 mutation (RUNX1⁺) and 388 without the mutation (RUNX1^-), were analyzed
  • The majority of patients (86%) had de novo AML
• Median age was 56.9 years (18.3–76.9)
• 75.7% of patients had intermediate risk cytogenetics and 24.3% had poor
• Most transplants were from matched unrelated donors (73.2%)
• Median follow-up after HSCT for RUNX⁺ and RUNX^- was 16.4 and 19.8 months, respectively
• Patient characteristics were similar between RUNX⁺ and RUNX^- groups, except for increased frequency of NPM1 mutations in the RUNX^- group (26% vs 6%) and ASXL1 mutations in the RUNX⁺ group (50% vs 16%)

Results

• Leukemia-free survival (LFS) and OS at 2 years were statistically different between the RUNX^- and RUNX⁺ groups (57.1% vs 63.7%, p= 0.18 and 62.8% vs 77.7%, p= 0.06, respectively) in patient with allo-HSCT in CR1
• Impact of mutational status on patient outcome
  • RUNX1 had no impact
  • FLT3-ITD was associated with increased risk of relapse, lower LFS and graft-versus-host disease/relapse free survival (GRFS)
• Results of the multivariate analysis of factors with a significant impact on patient outcome are presented in Table 2

Table 2. Multivariate analysis of factors with a significant impact on patient outcome (p values for the whole cohort)

GRFS, graft-versus-host disease/relapse free survival, LFS, leukemia-free survival; NRM, non-relapse mortality; OS, overall survival; TCD, T cell depletion
	Relapse	NRM	LFS	OS	GRFS
Unrelated vs related matched donor	–	0.00907	0.0293	0.0118	–
Age (per 10 year)	–	0.00001	0.00882	0.00932	–
Poor vs intermediate cytogenetics	0.0219	–	0.00432	–	0.0213
Female to male	–	0.0232	–	–	–
In vivo TCD	–	–	–	–	0.0288

Conclusions

The results of this retrospective study demonstrated that in contrast to secondary AML and MDS, in patients with de novo AML transplantation in CR1 may overcome the poor prognosis of RUNX1 mutation. It is possible that co-mutations in other genes could modify the impact of RUNX1.

Read about molecular profiling at diagnosis for risk stratification of patients with AML undergoing allo-HSCT in first remission here.

Other key abstracts from the TCT 2020 meeting

Other important abstracts mentioned in the webinar already covered on the AML Hub are listed in Table 3

Table 3. Other TCT meeting 2020 highlight abstracts

AML, acute myeloid leukemia; CIBMTR, Center for International Blood and Marrow Transplant Research; CPX-351, cytarabine and daunorubicin; GvHD, graft-versus-host disease; HSCT, hematopoietic stem cell transplantation; MAC, myeloablative conditioning; MDS, myelodysplastic syndromes; MRC, myelodysplasia-related changes; RIC, risk intensity conditioning; TCT, Transplantation & Cellular Therapy Meeting
Abstract title	Link to the article
Summary TCT 2020 highlights – part 1: Conditioning regimens for AML and MDS	https://aml-hub.com/medical-information/summary-tct-2020-highlights-part-1-conditioning-regimens-for-aml-and-mds
Outcomes in patients with AML with myelodysplasia-related changes (AML-MRC) who achieved remission with CPX-351 vs 7+3: phase III exploratory analysis	https://aml-hub.com/medical-information/subgroup-analysis-of-outcomes-in-patients-with-aml-mrc-who-achieved-remission-with-cpx-351-versus-7-3
MLL-rearranged AML is associated with poor outcomes as compared to patients with intermediate and adverse risk disease: A CIBMTR study of 3779 adult patients	https://aml-hub.com/medical-information/results-from-a-cibmtr-study-of-patients-with-mll-rearranged-aml
Long-Term follow up of BMT CTN0901, a randomised phase III trial comparing Myeloablative (MAC) to reduced intensity conditioning (RIC) prior to HSCT AML or MDS (MAC vs RIC trial)	https://aml-hub.com/medical-information/long-term-follow-up-from-mavric-trial