Practice Update: Oncology

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Long-Term Follow-Up of
Chemoimmunotherapy
With Rituximab,
Oxaliplatin, Cytosine
Arabinoside,
Dexamethasone in
Patients With Relapsed
CD20+ B-Cell NHL
American Journal of Hematology
Take-home message
• This phase II trial was designed to evaluate the
safety and efficacy of oxaliplatin in combination
with rituximab, cytarabine, and dexamethasone
(ROAD) in 45 patients with NHL who had relapsed
after one prior regimen. The overall response rate
was 71% (27% CR), and median overall survival was
26 months.
• These data demonstrate that ROAD is an acceptable
salvage regimen for patients with relapsed NHL.
Abstract
Patients with relapsed aggressive non-Hodgkin lymphoma (NHL)
are often treated with platinum-based chemoimmunotherapy
regimens in preparation for autologous stem cell transplant. We
sought to reduce toxicity and maintain efficacy by using oxalip-
latin with rituximab, cytarabine and dexamethasone (ROAD) in
a phase II clinical trial in patients who had relapsed after one
prior regimen. ROAD was delivered q21 days and consisted of
rituximab 375 mg/m(2) IV weekly x 4 doses (cycle 1 only); dexa-
methasone 40 mg PO/IV d2 - 5; oxaliplatin 130 mg/m(2) IV day
2; cytarabine 2000 mg/m(2) IV × two doses on days 2 to 3; and
pegfilgrastim 6 mg SC on day 4. Forty-five eligible patients were
accrued between 2006 and 2008. Patient characteristics were
a median age of 69 years; 96% had received prior rituximab;
53% were within one year of diagnosis. The median number of
cycles received was 2 (range, 1-6). Forty-four % received ROAD
as an outpatient. The overall response rate was 71% with 27%
(12/45) CR and 44% (20/45) PR. Forty-four % (20/45) of all patients
and 69% (18/26) of patients whom responded after 2 cycles
proceeded to transplant. Median overall survival was 26 mos
(95% CI: 7.3 mos-not reached) and median progression-free sur-
vival was 11 mos (95% CI: 6-104 mos). There was no grade 3/4
nephrotoxicity; the rate of grade 3/4 neuropathy was 4%. For-
ty-two percent of all patients and 69% of patients transplanted
remain alive at 5 years. ROAD represents an acceptable salvage
therapeutic option for patients with relapsed aggressive NHL.
Long-term follow-up of chemoimmunotherapy with rituximab,
oxaliplatin, cytosine arabinoside, dexamethasone (ROAD) in
patients with relapsed CD20+ B-cell non-Hodgkin lymphoma:
results of a study of the Mayo Clinic Cancer Center Research
Consortium (MCCRC) MC0485 now known as Academic and
Community Cancer Research United (ACCRU). Am J Hematol
2017 Jun 14;[EPub Ahead of Print], TE Witzig, PB Johnston, BR
LaPlant, et al.
Novel CompositeModel to
Estimate Risk of Mortality
in AML
JAMA Oncology
Take-home message
• This multisite, retrospective cohort study developed and vali-
dated a composite model to estimate the risk of 1-year mortality
among patients with acute myeloid leukemia (AML). Augmenting
the hematopoietic cell transplantation comorbidity index (HCT-CI)
with thrombocytopenia, hypoalbuminemia, and high LDH levels
improved the AUC and C-statistic compared with the AML comor-
bidity index. Adding cytogenetic/molecular risks and age to the
model further improved predictions.
• This study demonstrated that comorbidities have a significant
impact on 1-year mortality after initial therapy for AML. Additionally,
an augmented HCT-CI is the index best suited for comorbidity
evaluation in AML. Lastly, an AML composite model of augmented
HCT-CI, age, and cytogenetic/molecular risks has a strong AUC of
0.76 for 1-year mortality.
Abstract
IMPORTANCE To our knowledge, this multicenter analysis is the first to test and
validate (1) the prognostic impact of comorbidities on 1-year mortality after initial
therapy of acute myeloid leukemia (AML) and (2) a novel, risk-stratifying compos-
ite model incorporating comorbidities, age, and cytogenetic and molecular risks.
OBJECTIVE To accurately estimate risks of mortality by developing and validat-
ing a composite model that combines the most significant patient-specific and
AML-specific features.
DESIGN, SETTING, AND PARTICIPANTS This is a retrospective cohort study. A series of
comorbidities, including those already incorporated into the hematopoietic cell
transplantation-comorbidity index (HCT-CI), were evaluated. Patients were randomly
divided into a training set (n=733) and a validation set (n=367). In the training set,
covariates associated with 1-year overall mortality at a significance level of P<.10
constructed a multivariate Cox proportional hazards model in which the impact of
each covariate was adjusted for that of all others. Then, the adjusted hazard ratios
were used as weights. Performances of models were compared using C statistics
for continuous outcomes and area under the curve (AUC) for binary outcomes.
EXPOSURES Initial therapy for AML.
MAIN OUTCOMES AND MEASURES Death within 1 year after initial therapy for AML.
RESULTS A total of 1100 patients, ages 20 to 89 years, were treated for AML between
January 1, 2008, and December 31, 2012, at 5 academic institutions specialized
in treating AML; 605 (55%) were male, and 495 (45%) were female. In the valida-
tion set, the original HCT-CI had better C statistic and AUC estimates compared
with the AML comorbidity index for prediction of 1-year mortality. Augmenting the
original HCT-CI with 3 independently significant comorbidities, hypoalbuminemia,
thrombocytopenia, and high lactate dehydrogenase level, yielded a better C sta-
tistic of 0.66 and AUC of 0.69 for 1-year mortality. A composite model comprising
augmented HCT-CI, age, and cytogenetic/molecular risks had even better pre-
dictive estimates of 0.72 and 0.76, respectively.
CONCLUSIONS AND RELEVANCE In this cohort study, comorbidities influenced 1-year
survival of patients with AML, and comorbidities are best captured by an aug-
mented HCT-CI. The augmented HCT-CI, age, and cytogenetic/molecular risks
could be combined into an AML composite model that could guide treatment
decision-making and trial design in AML. Studying physical, cognitive, and social
health might further clarify the prognostic role of aging. Targeting comorbidities
with interventions alongside specific AML therapy might improve survival.
Development and validation of a novel acute myeloid leukemia-composite
model to estimate risks of mortality. JAMA Oncol 2017 Sep 07;[EPub Ahead of
Print], ML Sorror, BE Storer, AT Fathi, et al.
HEMATOLOGY 31
VOL. 1 • NO. 3 • 2017