Practice Update: Oncology

HEMATOLOGY 31

Novel CompositeModel to Estimate Risk of Mortality in AML 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. www.practiceupdate.com/c/57993 JAMA Oncology

Long-Term Follow-Up of Chemoimmunotherapy With Rituximab, Oxaliplatin, Cytosine Arabinoside, Dexamethasone in Patients With Relapsed CD20+ B-Cell NHL 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. www.practiceupdate.com/c/57377 American Journal of Hematology

VOL. 1 • NO. 3 • 2017