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Dr Isabel Cunningham discusses her top
abstracts fromASH 2016
Isabel Cunningham, MD, is Adjunct Associate Research Scientist,
Division of Hematology Oncology, Columbia University College
of Physicians and Surgeons in New York, and Associate Editor of
PracticeUpdate Oncology
.
Acute myeloid leukaemia: novel
therapy, excluding transplantation
Abstract 102:
Safety and efficacy of
venetoclax plus low-dose cytarabine in
treatment-naive patients aged ≥65 years with
acute myeloid leukemia.
A Wei, SA Strickland,
GJ Roboz, et al
This study enrolled 20 patients with treatment-
naive AML (expansion, n=12; escalation,
n=8) with a median age of 74 years who
were ineligible for anthracycline-containing
induction chemotherapy. The median time
on venetoclax was 147.5 days. The most
commonly reported grade 3/4 AEs included
febrile neutropenia (35%), hypophosphatemia
(20%), and hypertension (20%). Venetoclax
exposures both with and without low-dose
cytarabine were comparable. Of the 15 of
patients who achieved an objective response,
14 had a CR+CRi, all of whom had no prior
myeloproliferative neoplasm. For all patients,
the 12-month OS was 74.7%; for responders,
12-month OS was 86.7%.
These findings demonstrate the safety of
venetoclax plus low-dose cytarabine in older
patients with treatment-naive AML and sug-
gest that the improved survival in responders
is due to treatment with venetoclax plus low-
dose cytarabine.
Acute lymphoblastic leukaemia:
therapy, excluding transplantation
Abstract 176:
Final results of Northern
Italy Leukemia Group (NILG) Trial 10/07
combining pediatric-type therapy with minimal
residual disease study and risk-oriented
hematopoietic cell transplantation in adult
acute lymphoblastic leukemia (ALL).
R Bassan,
A Masciulli, T Intermesoli, et al
This study included 205 patients withALL (42
Ph+ ALL, 119 Ph− B-ALL, and 44 T-ALL)
with a median age of 41 years who received
combined paediatric-type therapy (PTT) with
minimal residual disease (MRD) study for risk-
oriented HCT. The CR rate was 98% in T-ALL
and Ph+ ALL, whereas the CR rate was 83%
in Ph− B-ALL, with a significantly higher rate
in patients
≤
60 years. In 109/142 CR patients
with Ph−ALL, theMRD study was successful
and contributed to risk classification in 41
MRD-responsive and 22 MRD-resistant
patients. Overall, the maintenance allocation
group consisted of 55 CR patients, and the
HCT allocation group included 87 patients,
with 43% selected for HCT independently
of MRD results. Intention-to-treat analyses
revealed overall survival of 53% at 5 years,
with the median not reached; the median
DFS is 4.8 years. Patients with Ph− ALL
had 5-year OS/DFS rates of 74%/61% in
T-ALL (medians not reached) and 48%/48%
in B-ALL (medians, 3.9 and 4.7 years). DFS
was significantly improved in patients with an
MRD response <10
−4
compared with patients
with MRD
≥
10
−4
.
These findings support the applicability of
the combined PTT/MRD-based risk-oriented
strategy in adults with ALL, with some
decreased effects in patients >60 years.
CLL: therapy, excluding
transplantation
Abstract 232:
Early achievement of MRD-
negativity in IGHV-mutated (IGHV-M) patients
portends highly favorable outcomes after
first-line treatment of CLL with fludarabine,
cyclophosphamide and rituximab (FCR).
Serial monitoring for minimal residual disease
(MRD) in blood after achieving MRD-negativity
predicts subsequent clinical relapse.
PA
Thompson, P Strati, M Keating, et al
This prospective study included 289 patients
with CLL who received first-line FCR
between 2008 and 2015 to evaluate the time
course and predictive factors for relapse in
initially MRD-negative patients. A total of 95
MRD-negative patients underwent 12-month
serial MRD blood monitoring. In the total
cohort, only IGHV-unmutated (IGHV-UM)
was significantly associated with PFS. Upon
separate analysis, IGHV-mutated (IGHV-M)
patients demonstrated a significant association
between ZAP70 positivity and shorter PFS,
whereas IGHV-UM patients demonstrated
a significant association between B2M
≥
4.0
mg/L and shorter PFS. The overall response
rate was 96%, with 51% of patients at EOT
achieving MRD negativity in bone marrow,
which was significantly associated IGHV-M
in multivariable analysis. In blood, re-
emergence of MRD was detected in 45/95
MRD-negative patients after a median of 49
months following treatment, which preceded
clinical relapse by a median of 25 months.
This study demonstrates that IGHV-M is
the best pretreatment predictor of achieving
MRD negativity and longer PFS; however,
many patients relapse, which can be moni-
tored in peripheral blood to direct interven-
tion strategies.
Clinical allogeneic transplantation:
results
Abstract 521:
Combining flow cytometry
and molecular assessment improves the
prognostic value of pre-transplant minimal
residual disease in acute myeloid leukemia.
F Guolo, P Minetto, F Galaverna, et al
This retrospective study evaluated out-
comes of 224 consecutive AML patients
who received allo-BMT in first or second
CR. Relapse occurred in 27.7% of patients.
Combined MRD analysis and onset of acute
GVHD were significant predictors of cumu-
lative incidence of relapse. MRD evaluation
predicted long-term survival, with significant
influences of conditioning intensity and com-
bined MRD evaluation on OS duration.
These results demonstrate that pretransplant
MRD evaluation via molecular and multi-
colour flow cytometry assessment reliably
predicts risk of relapse, which may be used
to tailor therapeutic strategies for patients.
Acute myeloid leukaemia: clinical
studies
Abstract 591:
Vadastuximab talirine plus
hypomethylating agents: a well-tolerated
regimen with high remission rate in frontline
older patients with acute myeloid leukemia
(AML).
AT Fathi, HP Erba, JE Lancet, et al
This phase 1 study included 53 patients with
previously untreated CD33-positive AML
who received vadastuximab talirine (33A)
plus hypomethylating agents to evaluate the
safety, tolerability, pharmacokinetics, and
antileukemic activity. The median treatment
duration currently is 19.3 weeks, with 13
patients continuing treatment. No dose-
limiting toxicities, infusion reactions, or
grade 4/5 bleeding were reported. Grade 3/4
adverse events included thrombocytopenia,
anaemia, febrile neutropenia, pneumonia,
and leukopenia. Non-haematological AEs
included fatigue, nausea, constipation,
pyrexia, dyspnoea, and diarrhoea. No
treatment-related deaths were reported. Of
the 49 evaluable patients, 73% achieved
CR or CRi. Of the 22 evaluable patients
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