Annual Meeting Proceedings Part 1 - American Society of Clinical ...

448s Leukemia, Myelodysplasia, and Transplantation
6628 General Poster Session (Board #27A), Mon, 1:15 PM-5:15 PM
Regional variation in treatment costs and survival for elderly patients with
myelodysplastic syndromes. Presenting Author: Xiaomei Ma, Yale University
School of Medicine, New Haven, CT
Background: Myelodysplastic syndromes (MDS) occur primarily in the
elderly (�65 years). The expected 5-year cost for an elderly MDS patient
tops $63,200 in 2009 US$. This study assessed regional variation in the
cost of care and survival for elderly MDS patients. Methods: Using the
Surveillance Epidemiology and End Results–Medicare data, we identified
primary MDS patients aged 66-99 years diagnosed from 2001-2007, had
continuous fee-for-service coverage for Parts A and B, and had no history of
other cancer. We assigned patients to Dartmouth Atlas of Health Care
Hospital Referral Regions (HRRs) based on their residence at time of
diagnosis. We also selected controls from a 5% sample of Medicare
beneficiaries without cancer and matched controls 1:1 to patients by HRR,
age, sex, pre-diagnosis cost and comorbidity. All Medicare claims through
2009 were tallied, and MDS-related costs were defined as the difference
between the payments for a patient and a matched control. Results: With
6244 patients in 73 HRRs, the average 3-year MDS-related cost varied
across HRRs, ranging from $12,900 to $83,600 (2009 US$). Patients in
high-spending regions had more comorbidities and higher Medicare costs
before diagnosis and were more likely to be racial minorities and live in
lower-income areas. Three-year survival ranged from 13.0% to 62.1%.
However, there was no significant correlation between 3-year costs and
3-year survival (��-0.06, p�0.61). The hazard ratios (HR) for higher
spending regions compared to the lowest-expenditure region were near 1,
after controlling for covariates including MDS subtype (2nd quartile:
HR�1.03, 95% CI: 0.94-1.12; 2nd quartile: HR�1.04, 95% CI: 0.95-
1.14; 4th quartile: HR�0.98, 95% CI: 0.90-1.08). Conclusions: We
observed considerable regional variation in Medicare expenditure on elderly
MDS patients during the first 3 years post-diagnosis. However, patients in
higher cost regions had similar 3-year survival to patients in lower cost
regions. Given the substantial economic burden of MDS and Medicare’s
current fiscal challenges, it is important to further assess the factors
associated with higher regional costs and to improve the care of MDS
patients in a cost-efficient way.
6630 General Poster Session (Board #27C), Mon, 1:15 PM-5:15 PM
Preliminary safety and efficacy of ruxolitinib in patients (pts) with primary
and secondary myelofibrosis (MF) with platelet counts (PC) of 50–
100x109 /L. Presenting Author: Moshe Talpaz, Comprehensive Cancer
Center, University of Michigan, Ann Arbor, MI
Background: Ruxolitinib (RUX) has demonstrated clinical benefit as therapy
for MF. This study explores the safety and efficacy of RUX in pts with MF
and low PC, where clinical data are limited. Methods: In this phase II study,
pts with intermediate-1 to high-risk MF, and PC of 50–100x109 /L started
RUX at 5 mg BID. Doses could be increased in 5 mg QD increments every 4
weeks (wks) beginning at wk 4. Doses were decreased or held for PC
�35x109 /L and �25x109 /L respectively. Assessments: Total Symptom
Score (TSS, using the modified MF Symptom Assessment Form v2.0, and
comprised of scores from 0�absent to 10�worst imaginable for night
sweats, itching, bone/muscle pain, early satiety, abdominal discomfort and
pain under left ribs); Patient Global Impression of Change (PGIC, a 7-point
scale ranging from “very much improved” to “very much worse”); spleen
size by palpation and by MRI (data not yet available); and safety. Results: At
the time of analysis, 23 pts had completed �4 wks on study. At baseline:
mean PC�72x109 /L; high (4%), intermediate-2 (52%) and intermediate-1
(44%) risk group; mean spleen length�16.6 cm; mean TSS�25.5. At the
time of analysis, 4%, 40%, 26%, 26% and 4% of pts were receiving RUX 5
mg QD, 5 mg BID, 5 mg AM/10 mg PM, 10 mg BID, and 10 mg AM/15 mg
PM, respectively. At wk 4 (all pts on 5 mg BID), mean TSS improved 14%;
13% had �50% improvement. At wk 8 (52% on 5 mg AM/10 mg PM),
mean TSS improved 23%; 30% had �50% improvement. Mean spleen
length reduction of 22% (wk 4) and 27% (wk 8) was observed, and PGIC
scores of “much improved” or “very much improved” were reported in 35%
(wk 4) and 39% (wk 8) of pts. There were no Grade 4 PC, no dose holds for
AEs and no discontinuations; 1 pRBC transfusion-dependent pt had Grade
4 anemia. Three pts experienced a total of 4 SAEs (fever; hypnagogic
dreams; and spleen pain/pneumonitis) which resolved while on treatment.
Conclusions: Effects on spleen size, PGIC, and TSS, even over the first
weeks at low doses, are superior to those observed in the placebo group in
the COMFORT-I study. These preliminary findings suggest a dosing strategy
starting with 5 mg BID RUX with subsequent dose optimization may be
efficacious and well tolerated in MF pts who have low platelets.
6629 General Poster Session (Board #27B), Mon, 1:15 PM-5:15 PM
History of autoimmunity to predict clinical response to DNA methyltransferase
inhibitors (DNMTI) in myelodysplastic syndromes (MDS), and
MDS-derived acute myeloid leukemias (AML). Presenting Author: Ashkan
Emadi, The Johns Hopkins University, Baltimore, MD
Background: MDS is comprised of a heterogeneous group of clonal myeloid
disorders. Chronic immune stimulation has been reported as a trigger for
the development of a subset of MDS, with increased autoreactive cytotoxic
T cells present in the bone marrow. Autoimmunity has been associated with
MDS and other marrow failures. DNMTIs, 5-azacytidine and decitabine, are
approved for the treatment of MDS. In addition to epigenetic impacts,
these agents may have immunomodulatory effects, including augmentation
of MAGE-related anti-tumor response. These reports and clinical observations
led us to hypothesize that MDS patients with a history of autoimmunity
may be more responsive to DNMTIs. Methods: To identify patients with
MDS, a retrospective database review (2007-2011) was performed at
Johns Hopkins Hospital (JHH) and Massachusetts General Hospital (MGH).
The MGH data also included those with AML whose disease had progressed
from MDS. Past medical history of autoimmune disorders, diagnosis, blood
counts, flow cytometry and cytogenetics were reviewed. Patients with
aplastic anemia, paroxysmal nocturnal hemoglobinuria or non-malignant
etiologies of cytopenia were excluded. Patients with MDS were further
studied if they were treated with DNMTI. Results: Of 137 patients with MDS
or MDS/AML, 23 had a documented history of autoimmunity in the medical
record. Of these, 15 (65.2%) experienced a response to therapy as defined
by the International Working Group. Of 114 patients without a documented
history of autoimmunity, 34 (29.8%) achieved a response during therapy, a
significantly lower percentage as compared to those with autoimmune
conditions (p-value 0.002, t-test). The majority of responding patients with
a history of autoimmunity displayed a normal karyotype (9 of 15 patients).
Conclusions: A history or co-presence of an autoimmune disorder may
predict a high likelihood of achieving a clinical response to DNMTIs.
Correlative studies in this unique population of patients with MDS and
MDS/AML and prospective clinical studies are needed to improve our
understanding of the possible mechanism of action of DNMTIs in these
patients.
6631 General Poster Session (Board #28A), Mon, 1:15 PM-5:15 PM
Correlation of TCR diversity with immune reconstitution after cord blood
transplant. Presenting Author: Ryan Emerson, Adaptive Biotechnologies,
Seattle, WA
Background: Umbilical cord blood is an important source of hematopoietic
stem cells for allogeneic transplants used to treat hematologic disorders
and malignancies. Stem cells from cord blood has several advantages over
other sources (peripheral blood or marrow) including reduced incidence of
graft-versus-host disease (GvHD) which allows less strict donor-patient
HLA-type matching requirements. However, hematopoietic recovery (both
myeloid and platelet engraftment) and immune reconstitution is significantly
delayed in CBT patients resulting in patients remaining at high risk
of infection for an extended period of time. Though the high risk of
infections to patients is well-documented and recognized, physicians lack
an objective means to monitor each patient’s progress toward functional
reconstitution of the adaptive immune system. Our project aims to test if
our measure of TCR diversity is a better proxy of immune reconstitution in
CBT patients. Methods: To do this, we compare our proposed measure of
immune reconstitution, TCRB CDR3 sequence diversity and richness over
time, against the observed clinical course of severe infection in patients
who have received CBT. Previously, peripheral blood mononuclear cells
(PBMC) were collected and cyropreserved from 35 CBT recipients at six
time points, pre-transplant, and 28, 56, 100, 180, and 365 days
post-transplant. Concordantly, clinical outcomes for these patients were
collected for up to four years post-transplant. We use a t-test to test if size
of TCR repertoire differs between CBT patients with non-relapse related
mortality and all other CBT patients. Results: Our TCR sequencing method
was successful at measuring immune reconstitution, and TCR diversity is
predictive of subsequent mortality from severe infection by 56 days
post-transplant. Conclusions: TCR repertoire sequencing is a viable method
to monitor immune reconstitution.
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