KK.Vyx

Question 1

Patients w MRC who presented wo antecedent heme disorder

Answer 1

78%

Question 2

how does MRC present?

Answer 2

As denovo AML with MDS related cytogenetic changes OR

As multilineage dysplasia

Question 3

% of patients with MRC presenting with AHD

Answer 3

22%

Question 4

Common unfavorable cytogenetic risk group in AML

Answer 4

del 5, del 7

Question 5

24-35% of all AML cases

Answer 5

AML MRC

Question 6

definition of MRC?

Answer 6

> 20% blasts in PB / Marrow and Any of the following:

MDS, Non MDS (MRC + Multilineage dysplasia)

Question 7

Multilineage dysplasia

Answer 7

Dysplasia in >50% of cells in at least 2 myeloid lines, UNLESS an NPM1 mutation or Biallelic mutation of CEBPA is present.

Question 8

MRC Characteristics?

Answer 8

Complex karyotype - 3 or more abnormalities

Unbalanced Abnormalities

Balanced Abnormalities

Question 9

Trial?

Answer 9

309 patients aged 60-75

Question 10

Primary endpoint

Answer 10

OS

Question 11

Phase 3 study patients?

Answer 11

20% T Aml
54% MRC w/ documented history
25% MRC No documented history

Question 12

FLT3 in 5 yr analysis

Answer 12

16% in Vyxeos Arm

Question 13

Prior HMA exposure?

Answer 13

41% patients treated with Vyxeos had prior HMA exposure

Question 14

Most frequently reported hemorraghic event

Answer 14

Epistaxis

Question 15

Primary end point

Answer 15

mOS 9.6 vs 5.9

Question 16

Hazard Ratio

Answer 16

0.69

Question 17

1 yr survival

Answer 17

42% vs 28%

Question 18

5yr survival

Answer 18

18% vs 8%

Question 19

At 5 years mOS in 60-69 was?

Answer 19

9.6 vs 6.9

Question 20

At 5 years mOS in 70-75 was?

Answer 20

8.9 vs 5.6

Question 21

In phase 3 % of patients achieving CR+CRi?

Answer 21

48% vs 33%

Question 22

% of patients achieving CR only?

Answer 22

38% vs 26%

Question 23

At 5 yrs mOS in patients achieving CR+CRi was?

Answer 23

21.7 mos vs 10.4 mos

Post Hoc analysis

small non randomized group 125

Question 24

Overall rate of HSCT

Answer 24

35% vs 25%

Question 25

How can we do a transplant better? Does it matter what induction / consolidation therapy used when taking a patient to transplant?

Answer 25

TBD

Question 26

Median OS in patients who received HSCT

Answer 26

Not reached vs 10.3 months

Question 27

Median OS in patients achieving CR or CRi

Answer 27

Not reached vs 11.7 mos

Question 28

MRD negativity? assessed after Vyxeos induction

Answer 28

Real World: Germany 64% by Flow 36 patients Italy 38% France 57% Flow NGS qPCR

Question 29

Patients w CR or CRi but no transplant

Answer 29

med OS for those in CR: 19.2 vs 8.4 mo med OS for those in CR+CRi: 14.7 vs 7.6

Question 30

30/60 day mortality

Answer 30

30: 6 vs 11% 60: 14 vs 21%

Question 31

Outpatient Admin?

Answer 31

64% IPOP then admitted day 6 (n=22) Kubal Study 58% IPOP eventually admitted (n=12) Deutch Study

Question 32

Overall incidence of hemorrhagic events was ___in the Vyxeos arm and ___in the control arm

Answer 32

74%, 56%

Question 33

Grade 3 or greater events occurred in ____

Answer 33

12% of Vyxeos treated patients.

Question 34

Fatal treatment emergent CNS hemorrhage not in the setting of progressive disease occurred in ___

Answer 34

2%

Question 35

Unbalanced Abnormalities

Answer 35

del 7 del 5 17q del 13, 11q, 12p

Question 36

Balanced abnormalities

Answer 36

t 11;16 t 3;21 t 1;3

Question 37

CPX is an integrated proposition

Answer 37

To include: Induction Consolidation Transplant

Question 38

% patients transplanted in Viale A

Answer 38

10%

Question 39

De Novo AML Mutations

Answer 39

NPM1, CEBPA, FLT3 ITD, Inv 16, t(8;21) aberrations involving 11q23

Question 40

Secondary type AML mutations stAML

Answer 40

RUNX1, EZH2, SRSF2, STAG2, ZRSR2, SF3B1, ASXL1, U2AF1

Question 41

2016 WHO classification of secondary AML

Answer 41

categorizes secondary AML together with de novo AML with myelodysplasia or related karyotypes

Question 42

Potential uses for AML MRD

Answer 42

1-Deep quantification of antileukemic efficacy 2.Early relapse detectionand intervention during sequential monitoring 3.Therapeutic assignment 4. Patient selection for clinical trials 5. As surrogate endpoint fo OS for regulatory approval

Question 43

AML is a _____

Answer 43

Collection of myeloid malignancies which can have changing clonal proportions over time.

Question 44

best test for MRD

Answer 44

Not at this time. Optimal would be a on size fits all approach to MRD monitoring.

Question 45

MRD monitoring best for?

Answer 45

APL, CML, MM single variants expressed at the transcript level - CML (bcr-abl) MM with distinct cell surface phenotypes

Question 46

In the German Experience patients achieving a CR+CRi had an MRD detected by flow of

Answer 46

64%

Question 47

in the Italian experience those achieving CR+CRi achieved a MRD detected by wt-1 mrd and mfc of

Answer 47

55% and 38% respectively

Question 48

In the french experience patients with CR +CRi MRD by flow,ngs,pcr

Answer 48

MRD of 57%