Haematology+Oncology_News

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KIR2DL5B genotype predicts outcome in chronic phase CML
BY JENNIFER SHEPPHIRD
Frontline Medical News
From Blood
The presence of KIR2DL5B was
associated with lower rates
of major molecular response
(MMR), transformation-free sur-
vival, and event-free survival (but
not overall survival) in patients
with chronic phase-chronic myeloid
leukaemia (CP-CML) treated with
sequential imatinib/nilotinib, ac-
cording to researchers.
Univariate analysis demonstrated
a significant association between
KIR2DL5B and achievement
of a major molecular response,
with hazard ratio 0.423 (95% CI,
0.262–0.682; P < 0.001). Other
KIR genotypes, KIR2DL2pos and
KIR2DS3pos, were also associated
with inferior achievement of MMR,
probably because of their associa-
tion with KIR2DL5B due to linkage
disequilibrium among KIR genes,
according to the investigators.
“Our findings suggest that even
with the potent second-generation
TKI [tyrosine kinase inhibitor] nilo-
tinib, KIR genotypes, a predeter-
mined genetic host factor, may still
be one of the most discriminatory
prognostic markers available at base-
line,” wrote Dr David T. Yeung of the
department of genetics and molecu-
lar pathology, Centre for Cancer Bi-
ology and the University of Adelaide,
South Australia, and colleagues
(Blood 2015 Dec 17. doi:10.1182/
blood-2015-07-655589).
Killer immunoglobulin-like recep-
tors (KIRs) contribute to natural killer
(NK) cell-mediated killing of tumour
cells, in both activating and inhibi-
tory roles. Normal cells are spared
through actions of inhibitory KIRs.
Although the mechanism underlying
the association between KIR2DL5B
and CP-CML treatment outcomes
is still unclear, the gene encodes an
inhibitory KIR receptor, the absence
of which may increase efficiency of
NK-mediated killing of leukaemic
stem cells, researchers suggested.
The Therapeutic Intensification
in De Novo Leukaemia (TIDEL-II)
study included 210 patients with
CP-CML who were treated with
imatinib initially, and nilotinib sub-
sequently if predetermined molecu-
lar targets were not met. The KIR
substudy included 148 patients with
samples available for genotyping.
KIR genotype frequencies ob-
served in this study were similar to
other white populations reported in
the Allele Frequency Database.
Early molecular response was also
significantly associated with treat-
ment outcomes, independent of KIR
prognostic significance, and may add
additional prognostic information,
available 3 months after treatment
commences.
“In contrast, KIR2DL5B can iden-
tify, at baseline, the 20% of patients
with a transformation risk of [about]
10% over 2 years versus the 80% of
patients with a transformation risk
of less than 3%,” the authors wrote.
They suggest that KIR2DL5B, com-
bined with other predictive markers,
may enable targeted early interven-
tions to improve outcomes.
ACOG recommends against annual
cervical cancer screening
BY MICHELE G. SULLIVAN
Frontline Medical News
From Obstetrics and Gynecology
Cervical cancer screening should begin at
age 21 years and continue even beyond
a woman’s reproductive years, but yearly
testing is neither necessary nor recommended
for most women, according to new guidelines
issued by the American College of Obstetri-
cians and Gynecologists.
Since cervical cancer is “a rather indolent
disease,” more frequent testing is much more
likely to result in anxiety and unnecessary treat-
ment than in preventing cancers, according to
the document, which was published online in
Obstetrics and Gynecology (2016;127:e1–20).
“Annual screening leads to a very small
increase in cases of cancer prevented at the
cost of a very large excess of procedures and
treatments and should not be performed,”
members of the ACOG Committee on Prac-
tice Bulletins–Gynecology wrote. Excisional
procedures can confer an increased risk of
preterm birth – another serious consideration
when determining the frequency of screening.
And, wrote the committee, the psychosocial
aspects of earlier screening must also be taken
into account.
“The emotional effect of labelling an ado-
lescent with a sexually transmitted infection
and potential precancer must be considered,
because adolescence is a time of heightened
concern for self-image and emerging sexuality,”
they wrote.
Recommendations in this set of guidelines dif-
fer slightly from those published in 2015 by the
Society of GynecologicOncology (SGO) and the
American Society for Colposcopy and Cervical
Pathology (ASCCP). Both the SGO andACOG
documents take into account the recently ap-
proved HPV DNA test, which is indicated as a
primary cervical cancer screening tool.
The test detects 14 high-risk HPV types,
and specifically identifies HPV 16 and 18. A
positive result for either of those types should
prompt a colposcopy; women who test positive
for any of the other 12 high-risk types should
have a Pap test.
The SGO guidelines say that primary HPV
testing alone can be considered for women
beginning at age 25 years. The ACOG docu-
ment also notes that HPV testing alone can
be considered an alternative for women older
than 25 years but stresses that cytology alone
or co-testing remain the options specifically
recommended in current major society guide-
lines. If screening with the primary HPV test is
used, it should be performed according to the
SGO guidance, the ACOG document states.
Dr Jill Rabin favours the ACOG recommen-
dations over HPV-only testing. She is a profes-
sor of obstetrics and gynaecology and cochief
of the division of ambulatory care, Women’s
Health Programs – Prenatal Care Assistance
Program Services at Northwell Health, New
Hyde Park, New York
“I know certain groups – and not just SGO –
go with just the HPV-only test, but I can’t bring
myself to do that,” she said in an interview.
“Most of the literature agrees that you need to
look at both cytology and HPV testing to get
the best results. And all cervical cancer is not
driven by HPV infections.”
The ACOG document stresses that sexual
initiation – whatever the age – should not be
the precipitating factor for the first cervical
cancer screening. HPV infections are normally
acquired very quickly after vaginal intercourse
begins, although nearly all cases are naturally
cleared within a couple of years. From ages
21–29 years, cervical cytology alone is suffi-
cient for these women, and primary HPV co-
testing is not appropriate. The recommended
screening interval is every 3 years.
HPV testing is more sensitive than is cytol-
ogy but less specific, the authors said. And
because women in this age group often have
noncarcinogenic, transient HPV infections,
co-testing could drive more testing and inter-
ventions without decreasing cancer incidence.
For women aged 30–65 years, however, HPV
testing combined with cervical cytology is the
optimum choice and should be conducted every
5 years. If cytology alone is performed, however,
the recommended interval is every 3 years.
Any woman in this age group who has an
HPV-positive co-test with negative cytology
should be retested with both methods in 12
months. A colposcopy is recommended if the
repeat cervical cytology test result is unspeci-
fied atypical squamous cells or higher, or if the
HPV test result is still positive. Otherwise, the
next co-testing can occur 3 years later.
As an alternative strategy, an immediate
HPV genotyping can be performed; if high-risk
strains are present, an immediate colposcopy
is indicated.
A history of having had the HPV vaccine
series doesn’t obviate the need for screening or
change the basic recommendations for screen-
ing type or interval, according to the ACOG
document. Even the 9-valent vaccine doesn’t
cover all cancer-associated HPV. And many
women may have had the series after al-
ready acquiring an HPV infection, which
reduces the vaccine’s efficacy.
Finally, the ACOG committee noted
that, “long-term efficacy of the vaccine
remains incompletely established. Al-
though HPV vaccination is an important
step toward cervical cancer prevention,
it does not remove the need for routine
cervical cancer screening.”
After age 65 years, screening can be
discontinued for women with who have
had consecutive negative testing in the
prior 10 years. For women who have had
grade 2 or 3 cervical intraepithelial neo-
plasia (CIN), or adenocarcinoma in situ,
screening needs to continue for 20 years
after spontaneous regression or treatment.
“Women aged 65 years and older do get
cervical cancer,” the ACOG committee
members wrote. “Women in this age group
represent 14% of the US female popula-
tion but have 19.6% of the new cases of
cervical cancer.”
However, since most cases occur in
inadequately or unscreened women, and
because of the long latency of HPV-driven
cancers, “screening women in this age group
would prevent very few cases ... [and the
slight gain] would come at significant cost,
including an increase in required colposcopy
procedures.”
Changes in most risk factors, including
new sexual partners, are not a reason to start
screening again in older women because of the
long disease latency, according to the ACOG
recommendations. Dr Rabin added, “I recon-
sider this in certain instances if their status
changes, especially if there is immunosuppres-
sion, being with a high-risk partner, or having
multiple sexual partners.”
The guidelines recommend more frequent
screening for women previously treated for
CIN 2, CIN 3, or cancer; those with HIV
infection; those who are immunocompro-
mised, including have received solid organ
transplants; and those who were exposed to
diethylstilbestrol in utero.
Women who’ve had a total hysterectomy
and no history of CIN 2 or greater don’t need
screening, but those who have had a high-
grade CIN should continue it, as there can
be a recurrence in the vaginal cuff even years
later.
Even with the potent second-generation TKI [tyrosine kinase
inhibitor] nilotinib, KIR genotypes, a predetermined genetic
host factor, may still be one of the most discriminatory
prognostic markers available at baseline.
Haematology & O ncology News • Vol. 9 • No. 1 • 2016
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