TO THE EDITOR:

Tyrosine kinase inhibitors (TKIs) have profoundly affected the outcome of Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL).1-7 In the recent front-line GIMEMA LAL2116 protocol for adult patients with Ph+ ALL, with no upper age limit, induction of dasatinib was followed by a consolidation with 2 to 5 cycles of the bispecific monoclonal antibody blinatumomab.8,9

With this targeted and immunotherapeutic induction-consolidation strategy devoid of systemic chemotherapy, a complete hematologic response was observed in 98.4% of cases and a molecular response, identified by the number of BCR/ABL1 copies in 60% of patients after 2 cycles of blinatumomab, the primary end point of the study.10 Molecular responses further increased after additional blinatumomab cycles. Overall survival and disease-free survival were 95.2% and 88.3%, respectively, at a median follow-up of 18 months.10 We hereby report extensive...

1.
Ravandi
F.
How I treat Philadelphia chromosome-positive acute lymphoblastic leukemia
.
Blood.
2019
;
133
(
2
):
130
-
136
.
2.
Rousselot
P
,
Coudé
MM
,
Gokbuget
N
, et al;
European Working Group on Adult ALL (EWALL) group
.
Dasatinib and low-intensity chemotherapy in elderly patients with Philadelphia chromosome-positive ALL
.
Blood.
2016
;
128
(
6
):
774
-
782
.
3.
Yoon
JH
,
Yhim
HY
,
Kwak
JY
, et al
.
Minimal residual disease-based effect and long-term outcome of first-line dasatinib combined with chemotherapy for adult Philadelphia chromosome-positive acute lymphoblastic leukemia
.
Ann Oncol.
2016
;
27
(
6
):
1081
-
1088
.
4.
Vignetti
M
,
Fazi
P
,
Cimino
G
, et al
.
Imatinib plus steroids induces complete remissions and prolonged survival in elderly Philadelphia chromosome-positive patients with acute lymphoblastic leukemia without additional chemotherapy: results of the Gruppo Italiano Malattie Ematologiche dell’Adulto (GIMEMA) LAL0201-B protocol
.
Blood.
2007
;
109
(
9
):
3676
-
3678
.
5.
Foà
R
,
Vitale
A
,
Vignetti
M
, et al;
GIMEMA Acute Leukemia Working Party
.
Dasatinib as first-line treatment for adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia
.
Blood.
2011
;
118
(
25
):
6521
-
6528
.
6.
Chiaretti
S
,
Vitale
A
,
Vignetti
M
, et al
.
A sequential approach with imatinib, chemotherapy and transplant for adult Ph+ acute lymphoblastic leukemia: final results of the GIMEMA LAL 0904 study
.
Haematologica.
2016
;
101
(
12
):
1544
-
1552
.
7.
Chiaretti
S
,
Ansuinelli
M
,
Vitale
A
, et al
.
A multicenter total therapy strategy for de novo adult Philadelphia chromosome positive acute lymphoblastic leukemia patients: final results of the GIMEMA LAL1509 protocol
.
Haematologica.
2021
;
106
(
7
):
1828
-
1838
.
8.
Kantarjian
H
,
Stein
A
,
Gökbuget
N
, et al
.
Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia
.
N Engl J Med.
2017
;
376
(
9
):
836
-
847
.
9.
Topp
MS
,
Gökbuget
N
,
Zugmaier
G
, et al
.
Phase II trial of the anti-CD19 bispecific T cell-engager blinatumomab shows hematologic and molecular remissions in patients with relapsed or refractory B-precursor acute lymphoblastic leukemia
.
J Clin Oncol.
2014
;
32
(
36
):
4134
-
4140
.
10.
Foà
R
,
Bassan
R
,
Vitale
A
, et al
.
Dasatinib-blinatumomab treatment for adult Ph-positive acute lymphoblastic leukemia in adults
.
N Engl J Med.
2020
;
383
(
17
):
1613
-
1623
.
11.
Chiaretti
S
,
Bassan
R
,
Vitale
A
, et al
.
Updated results of the GIMEMA LAL2116 D-ALBA trial for newly diagnosed adults with Ph+ ALL [abstract]
.
HemaSphere.
2021
;
5
(
S2
):
e566
. Abstract S112.
12.
Trabolsi
A
,
Arumov
A
,
Schatz
JH.
T cell-activating bispecific antibodies in cancer therapy
.
J Immunol.
2019
;
203
(
3
):
585
-
592
.
13.
Willinger
T
,
Freeman
T
,
Hasegawa
H
,
McMichael
AJ
,
Callan
MF.
Molecular signatures distinguish human central memory from effector memory CD8 T cell subsets
.
J Immunol.
2005
;
175
(
9
):
5895
-
5903
.
14.
Torelli
GF
,
Guarini
A
,
Maggio
R
,
Alfieri
C
,
Vitale
A
,
Foà
R.
Expansion of natural killer cells with lytic activity against autologous blasts from adult and pediatric acute lymphoid leukemia patients in complete hematologic remission
.
Haematologica.
2005
;
90
(
6
):
785
-
792
.
15.
Torelli
GF
,
Peragine
N
,
Raponi
S
, et al
.
Recognition of adult and pediatric acute lymphoblastic leukemia blasts by natural killer cells
.
Haematologica.
2014
;
99
(
7
):
1248
-
1254
.
16.
Torelli
GF
,
Peragine
N
,
Mariglia
P
,
Foà
R.
The antileukemic potential of natural killer cells
.
Immunotherapy.
2016
;
8
(
4
):
425
-
434
.
17.
Mustjoki
S
,
Auvinen
K
,
Kreutzman
A
, et al
.
Rapid mobilization of cytotoxic lymphocytes induced by dasatinib therapy
.
Leukemia.
2013
;
27
(
4
):
914
-
924
.
18.
Kim
DH
,
Kamel-Reid
S
,
Chang
H
, et al
.
Natural killer or natural killer/T cell lineage large granular lymphocytosis associated with dasatinib therapy for Philadelphia chromosome positive leukemia
.
Haematologica.
2009
;
94
(
1
):
135
-
139
.
19.
Mustjoki
S
,
Ekblom
M
,
Arstila
TP
, et al
.
Clonal expansion of T/NK-cells during tyrosine kinase inhibitor dasatinib therapy
.
Leukemia.
2009
;
23
(
8
):
1398
-
1405
.
20.
Zugmaier
G
,
Gökbuget
N
,
Klinger
M
, et al
.
Long-term survival and T-cell kinetics in relapsed/refractory ALL patients who achieved MRD response after blinatumomab treatment
.
Blood.
2015
;
126
(
4
):
2578
-
2584
.
21.
Dwarakanath
BS
,
Farooque
A
,
Gupta
S.
Targeting regulatory T cells for improving cancer therapy: Challenges and prospects
.
Cancer Rep (Hoboken).
2018
;
1
(
1
):
e21105
.
22.
Suryadevara
CM
,
Desai
R
,
Farber
SH
, et al
.
Preventing Lck activation in CAR T cells confers Treg resistance but requires 4-1BB signaling for them to persist and treat solid tumors in nonlymphodepleted hosts
.
Clin Cancer Res.
2019
;
25
(
1
):
358
-
368
.
23.
Duell
J
,
Dittrich
M
,
Bedke
T
, et al
.
Frequency of regulatory T cells determines the outcome of the T-cell-engaging antibody blinatumomab in patients with B-precursor ALL
.
Leukemia.
2017
;
31
(
10
):
2181
-
2190
.
24.
Niedźwiecki
M
,
Budziło
O
,
Adamkiewicz-Drożyńska
E
, et al
.
CD4+CD25highCD127low/FoxP3+ regulatory T-cell population in acute leukemias: a review of the literature
.
J Immunol Res.
2019
;
2019
:
2816498
.
25.
Leonard
JT
,
Kosaka
Y
,
Malla
P
, et al
.
Concomitant use of a dual ABL/Src kinase inhibitor eliminates the in vitro efficacy of blinatumomab against Ph+ ALL
.
Blood.
2021
;
137
(
7
):
939
-
944
. .
26.
Batlevi
CL
,
Matsuki
E
,
Brentjens
RJ
,
Younes
A.
Novel immunotherapies in lymphoid malignancies
.
Nat Rev Clin Oncol.
2016
;
13
(
1
):
25
-
40
.
27.
Chiaretti
S
,
Vitale
A
,
Cazzaniga
G
, et al
.
Clinico-biological features of 5202 patients with acute lymphoblastic leukemia enrolled in the Italian AIEOP and GIMEMA protocols and stratified in age cohorts
.
Haematologica.
2013
;
98
(
11
):
1702
-
1710
.
You do not currently have access to this content.

Sign in via your Institution

Sign In