MPN, there is no convincing data to recommend venetoclax as therapy for patients with MPN
or post MPN-AML. Indeed, due to its possible activity in IDH-mutation positive patients,
venetoclax in combination with ivosidenib with or without azacitidine is being evaluated in
IDH1-mutated patients with advanced malignancies, including post-MPN AML and accelerated
MPN, in an ongoing phase 1/2 trial (NCT03471260) 14. On the other hand, given that Bcl-xL
is over-expressed in cells of patients with MPN, the Bcl-xL inhibitor navitoclax is being studies
in combination with JAK inhibitor ruxolitinib in MPN patients (phase 2 trial NCT03222609 and
phase 3 trial NCT 04472598).
References:
1. Pan R, Hogdal LJ, Benito JM, et al. Selective BCL-2 inhibition by ABT-199 causes on-target cell death
in acute myeloid leukemia. Cancer Discov. 2014;4(3):362-375.
2. DiNardo CD, Jonas BA, Pullarkat V, et al. Azacitidine and venetoclax in previously untreated acute
myeloid leukemia. N Engl J Med. 2020;383(7):617-629.
3. DiNardo CD, Maiti A, Rausch CR, et al. 10-day decitabine with venetoclax for newly diagnosed
intensive chemotherapy ineligible, and relapsed or refractory acute myeloid leukaemia: a single-centre,
phase 2 trial. Lancet Haematol. 2020;7(10):e724-e736.
4. Lin KH, Winter PS, Xie A, et al. Targeting MCL-1/BCL-XL forestalls the acquisition of resistance to
ABT-199 in acute myeloid leukemia. Sci Rep. 2016;6:27696.
5. Tahir SK, Smith ML, Hessler P, et al. Potential mechanisms of resistance to venetoclax and strategies
to circumvent it. BMC Cancer. 2017;17:399.
6. Konopleva M, Pollyea DA, Potluri J, et al. Efficacy and biological correlates of response in a phase II
study of venetoclax monotherapy in patients with acute myelogenous leukemia. Cancer Discov.
2016;6(10):1106-1117.
7. Petiti J, Lo lacono M, Rosso V, Andreani G, Jovanovski A, Podesta M, et al. Bcl-xl represents a
therapeutic target in Philadelphia negative myeloproliferative neoplasms. J. Cell Mol. Med.
2020:24:10978-10986.
8. DiNardo CD, Tiong IS, Quarlieri A, MacRaild S, Loghavi S, Brown FC, et al. Molecular patterns of
response and treatment failure after frontline venetoclax combinations in older patients with AML.
Blood 2020;135(11):791-803.
9. Gangat N, Morsia E, Foran JM, et al. Venetoclax plus hypomethylating agent in blast-phase
myeloproliferative neoplasm: preliminary experience with 12 patients. Br. J Haematol.
2020;191(5):e120-e124.
10. Tremblay D, Feld J, Dougherty M, et al. Venetoclax and hypomethylating agent combination therapy
in acute myeloid leukemia secondary to a myeloproliferative neoplasm. Leuk Res. 2020;98:106456.
11. Huemer F, Melchardt T, Jansko B, et al. Durable remissions with venetoclax monotherapy in
secondary AML refractory to hypomethylating agents and high expression of BCL-2 and/or BIM. Eur
J Haematol. 2019;102:437-441.
12. Masarova L, DiNardo CD, Bose P, Pemmaraju N., et al. Single center experience with Venetoclax
combinations in patients with newly diagnosed and relapsed acute leukemia evolving from
myeloproliferative neoplasms. Manuscript in preparation, 2021.
13. Chifotides HT, Masarova L, Alfayez M, Daver N, Alvarado Y, Jabbour E, et al. Outcome of patients
with IDH1/2-mutated post-myeloproliferative neoplasm AML in the era of IDH inhibitors. Blood
Adv. 2020;4(21):5336-5342.
14. Lachowiez CA, Borthakur G, Loghavi S, et al. Phase Ib/II study of the IDH1-mutant inhibitor
ivosidenib with the BCL2 inhibitor venetoclax +/- azacitidine in IDH1-mutated hematologic
malignancies. J Clin Oncol. 2020;38(suppl 15):7500.
SCIENTIFIC PROGRAMME
SESSION I
OPTIMIZING
CYTOREDUCTION
SESSION II
MANAGEMENT OF CML
WITH TKI
SESSION III
MPN RISK
STRATIFICATION
INCLUDING VASCULAR
EVENTS
DEBATE 1
INTERFERON ALPHA
SHOULD BE FRONT LINE
THERAPY IN ALL ET/PV
PATIENTS
ROUNDTABLE 1
INFECTIONS IN
MYELOPROLIFERATIVE
DISORDERS, INCLUDING
CML
ROUNDTABLE 2
PREGNANCY AND
PARENTING
DEBATE 2
ALLOGENEIC STEM CELL
TRANSPLANTATION
SHOULD BE CONSIDERED
THIRD LINE OPTION IN
CHRONIC PHASE CML
SESSION IV
EVOLVING THERAPIES
IN MYELOFIBROSIS
SESSION V
MANAGEMENT OF
ADVANCED AND UNUSUAL
DISEASE (MPN AND CML)
SESSION VI
TREATMENT FREE
REMISSION IN CML
KEYNOTE LECTURE
SELECTED ABSTRACTS
FOR AN ORAL
PRESENTATION
SELECTED ABSTRACTS
FO R A POSTER
PRESENTATION
DISCLOSURES