CLINICAL NEWS
expected,” he noted, at 41 percent, and “very few, 3 per-
cent, were grade 3 or 4.” Three percent and 4 percent of
patients in the daratumumab and Rd groups, respectively,
developed a secondary primary malignancy, and the
incidence of treatment-emergent adverse events leading
to death was 7 percent and 6 percent, respectively.
Dr. Facon noted that the overall survival data from
the MAIA trial are not yet mature, which limits compari-
sons between the daratumumab combination and other
regimens for the treatment of myeloma. For example,
bortezomib plus Rd has become a standard of care in
several countries, with a PFS of approximately 36 months.
Dr. Facon also acknowledged that other combina-
tions and maintenance regimens are associated with more
toxicity, making them unsuitable for older, frail patients –
like the population enrolled in MAIA. Regardless, he said,
“it is good for patients to have more than one option.”
The authors report financial relationships with KITE,
AbbVie, and Janssen, the sponsor of the trial.
REFERENCE
Facon T, Kumar SK, Plesner T, et al. Phase 3 randomized study of daratumumab plus lenalidomide
and dexamethasone (D-Rd) versus lenalidomide and dexamethasone (Rd) in patients with
newly diagnosed multiple myeloma (NDMM) ineligible for transplant (MAIA). Abstract #LBA-2.
Presented at the 2018 ASH Annual Meeting, December 4, 2018; San Diego, CA.
New Sickle Cell Disease
Screening Test Is
Highly Accurate – and
Inexpensive
In a population of young children in Uganda, a new screen-
ing test for sickle cell disease (SCD) that delivers point-of-
care results and costs $2 or less to perform was more than
99 percent accurate in detecting the disease, according to
results presented as a late-breaking abstract at the 2018 ASH
Annual Meeting. 1
Standard diagnostic tools for SCD are not suitable for
most parts of Africa, as they require expensive machin-
ery and large volumes of blood. This new “uncompli-
cated and rapid procedure” is ideal for limited-resource
regions; it takes just 10 minutes, six drops of water, and
one drop of blood to complete, study author Erik Serrao,
PhD, from Silver Lake Research Corporation in Azusa,
California, noted.
“Diagnostic screening for SCD in newborns and young
children – followed by treatment, prophylaxis, and counsel-
ing – has been shown to dramatically reduce the mortality of
this disease in higher-resource regions,” Dr. Serrao ex-
plained. “However, sickle cell screening has not been widely
implemented in Africa, so individuals with the disease are
commonly identified only after they die or when they pres-
ent at the hospital with life-threatening symptoms.”
In this study, investigators established an SCD screen-
ing program at a major hospital in southeastern Uganda,
an area where SCD accounts for approximately 20 percent
of childhood deaths each year.
Blood samples from 1,000 recruited children young-
er than 5 years old were run through HemoTypeSC and
a reference test, capillary zone electrophoresis (CZE),
which costs $12 to perform.
HemoTypeSC is a lateral flow assay that relies on highly
specific monoclonal antibodies for hemoglobin (Hb) A,
HbS, and HbC to diagnose SCD. The testing kit instructs
clinicians to place a drop of blood onto a paper strip, then
dip it into a vial with a few drops of blood. A test strip con-
taining the antibodies is then added to the test tube, where
it encounters the blood. In ten minutes, the paper strip
shows a specific test line if the patient has markers for SCD.
HemoTypeSC diagnostic results matched the results of
the reference test for 998 of the 1,000 specimens analyzed,
for an accuracy rate of 99.8 percent. Of these specimens,
720 were found to have HbAA by both HemoTypeSC
and CZE. Of the remaining 280 specimens, two yielded
discordant results, in which specimens identified as
HbSS (meaning both of the child’s parents had HbS
gene, denoting SCD) by CZE were identified as HbAS
ASHClinicalNews.org
Erik Serrao, MD, speaks at the 2018 ASH Annual Meeting.
(meaning one parent had HbS, denoting sickle cell trait) by
HemoTypeSC.
As part of the study protocol, investigators ran a
secondary analysis on tests with discordant results. When
parents were contacted to obtain another blood sample, re-
searchers learned that the two patients who had discordant
results had been diagnosed with HbSS and were recently
transfused with HbAA, which led to trace levels of HbA in
their blood. “Therefore, their true phenotype at the time
of testing was HbAS for both samples – as detected by
HemoTypeSC,” Dr. Serrao explained. When researchers
adjusted for these results, the accuracy improved to 100
percent.
Anecdotally, he said that clinicians in the program have
not reported any difficulty either in performing or reading
results from the test.
Although the results show that the HemoTypeSC test
is a promising screening tool, Dr. Serrao acknowledged
that “one limitation is that the youngest age screened
is 1 month, so we didn’t include any newborns in this
study.” However, he cited an earlier study that evaluated
HemoTypeSC in 57 newborns, in which the test had sensi-
tivity and specificity above 99 percent. 2
“SCD screening programs have been projected to be
cost-effective in Africa and could actually save significant
amounts of money for governments as [more of their]
budgets are allocated to screening and less to identify-
ing the disease after patients present with life-threatening
symptoms,” he concluded.
The authors report financial relationships with Silver
Lake Research Corporation, which developed HemoTypeSC
and supported this study.
REFERENCES
1. Nankanja R, Kiyaga C, Geisberg M, et al. Implementation of a Sickle Cell Disease Screening
Initiative in Uganda with HemoTypeSCTM. Abstract #LBA-3. Presented at the 2018 ASH Annual
Meeting, December 4, 2018; San Diego, CA.
2. Steele C, Sinski A, Asibey J, et al. Point-of-care screening for sickle cell disease in low-resource
settings: a multi-center evaluation of HemoTypeSC, a novel rapid test. Am J Hematol. 2018
October 5. [Epub ahead of print]
Ibrutinib Versus
FCR: A “Paradigm
Shift” for
Younger Patients
With Treatment-
Naïve CLL
In patients with previously untreated
chronic lymphocytic leukemia (CLL),
treatment with an ibrutinib-based therapy
improved progression-free survival (PFS)
and overall survival (OS), compared with
a standard chemoimmunotherapeutic
regimen of intravenous fludarabine,
cyclophosphamide, and rituximab (FCR),
according to results from the phase III
ECOG-E1912 trial.
Tait D. Shanafelt, MD, from Stanford
University in California presented the
results as a late-breaking abstract at the
2018 ASH Annual Meeting.
“The combination of fludarabine,
cyclophosphamide, and rituximab is the
most active therapy [in this setting], but
one with a high [incidence of] side ef-
fects that cannot be tolerated by all CLL
patients,” Dr. Shanafelt explained. FCR is
primarily used in patients younger than
70 years, but “since the median age at
diagnosis for this disease is around 65 to
70 years, half of the patients are not even
able to tolerate the therapy.”
With this trial, the researchers evalu-
ated “whether we could improve upon the
best current treatment for patients with
CLL,” he noted. The ECOG-E1912 study
enrolled 529 patients ≤70 years who were
diagnosed with CLL (without del17p) and
had no recorded history of prior therapy.
All patients had an ECOG performance
status of 0 to 2 and were able to tolerate
FCR.
In a 2:1 ratio, patients were random-
ized to one of either of the following treat-
ments, which were received every 28 days:
• Ibrutinib-rituximab: ibrutinib 420
mg daily plus rituximab (50 mg/m 2
on day 1 of cycle 2, followed by 325
mg/m 2 on day 2 of cycle 2 and 500
mg/m 2 on day 1 of cycles 3-7)
• FCR: fludarabine 25 mg/m 2 ,
cyclophosphamide 250 mg/m 2 on
days 1-3, and rituximab (50 mg/m 2
on day 1 of cycle 1, followed by 325
mg/m 2 on day 2 of cycle 1, and 500
mg/m 2 on day 1 of cycles 2-6)
The ibrutinib group included 354 patients,
while 175 were enrolled in the FCR arm.
Patient characteristics were similar
between the two treatment arms. The
median age was 57 in the ibrutinib group
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