VENETOCLAX-PONATINIB BASED TREATMENT IN REFRACTORY BLASTIC PHASE
OF CHRONIC MYELOID LEUKEMIA IN A PATIENT WITH SARS-COV-2-INFECTION
Fernanda Seganfredo1, Diana Viegas1, Joana Desterro2, Francesca Pierdomenico3 and Maria Gomes da
Silva1
(1)Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisboa, Portugal
(2)Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa,
Portugal
(3)Instituto Português de Oncologia de Lisboa, Francisco Gentil, Lisboa, Portugal
Chronic myeloid leukemia (CML) is commonly diagnosed in chronic phase. Patients presenting
in blast phase (BP) have inferior outcomes due to resistance to conventional treatment with
tyrosin kinases inhibithors (TKI). We report here the clinical case of a 42-year-old man with
Ph-positive CML who developed two BP during his clinical course.
The patient presented to another hospital with a history of fatigue, weight loss (10kg over 3
months), night sweats, leukocytosis and 30% myeloblasts (MB) on peripheral blood smear. An
acute leukemia was suspected but further investigation revealed CML-BP. At diagnosis,
fluorescence in situ hybridization (FISH) was positive for t(9,22) and conventional cytogenetics
showed 9/20 metaphases with t(9,22) (q34;q11), with no additional chromosomal alterations.
Patient was started on hydroxyurea to control leukocytosis and the introduction of Imatinib
was delayed for one month due to Grade 3-4 (G3-4) infectious complications. After three
weeks on Imatinib 400 mg/day, with good disease control, he developed (G4) peripheral
neuropathy and imatinib was suspended. He was then referred to our hospital, still presenting
fatigue and neuropathic pain. On physical examination, the patient was pale, cachectic, with
no organomegaly. Blood counts showed 32000 leucocytes/mcl with 2% MB. Bone marrow
(BM) aspirate and biopsy were repeated and showed features of chronic phase CML with 2.7%
blasts. FISH analysis detected BCR/ABL nuclear fusion signals in 94% of cells and classical
cytogenetic revealed additional alterations: 46, XY,t(9;22)(q34;q11)9/46,XY,der(1)t(1;9)
(p32~36,q34)t(9;22)(q34;q11),der(9)t(1;9),der(22)t(9;22)11. At that time, dasatinib 140mg
/day was started but had to be interrupted for 1-month due to G4 cytopenias; the drug was
restarted at 50mg/day. Response evaluation after 3-month showed 32% of MB in the BM and
additional karyotypic abnormalities (trisomy 8 in 10 cells) 46,XY,t(9;22)(q34;q11)8/47,XY,
der(1)t(1;9)(p32~36;q34)t(9;22)(q34;q11),+8,der(9)t(1;9),der(22)t(9;22)10/46,XY12
compatible with clonal evolution and 2nd blast crisis.
At that point patient received induction chemotherapy with the FLAG-IDA regimen. During
aplasia, he presented several infectious complications, including severe SARS-Cov2 infection
with prolonged mechanical ventilation (1 month) but complete resolution. Upon recovery of
peripheral blood counts a BM evaluation confirmed refractory disease with 43% MB. As soon
as oral intake became possible he started Ponatinib with dose adjustments for hematological
toxicity (G4 thrombocytopenia) and poor disease control. Bone marrow evaluation showed
persistent disease with 73% MB. The patient was proposed to a combination of ponatinib
(30mg/day), venetoclax (400mg/day) and decitabine as a bridge for allogenic transplant. He is
currently on his 4th cycle, with progressive reduction of blast counts.
POSTER 25
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