Old age (≤65 years), relapsed or refractory disease, and the presence of FMS-like receptor tyrosine kinase-3 (FLT3) internal tandem duplication (ITD) mutation are poor prognostic factors in acute myeloid leukemia (AML). FLT3 inhibitors such as sorafenib have been shown to have a potential role in treating relapsed or refractory AML with FLT3 mutations. In the present report, the use of sorafenib in combination with cytarabine and idarubicin resulted in disease control for 7 months in an older patient with relapsed FLT3-positive AML. This case report and the existing literature indicate that sorafenib has disease activity against relapsed AML with the FLT3-ITD mutation in older patients. Larger multicenter studies should be conducted to confirm these findings, which have the potential to improve outcomes in this high-risk AML subgroup.
Smith Giri, Shadi Hamdeh, Vijaya Raj Bhatt and James K. Schwarz
Andrew W. Hahn, Smith Giri, Dilan Patel, Heather Sluder, Ari Vanderwalde and Mike G. Martin
With the advent of widespread tumor genetic profiling, an increased number of mutations with unknown significance are being identified. Often, a glut of uninterpretable findings may confuse the clinician and provide little or inappropriate guidance in therapeutic decision-making. This report describes a method of protein modeling by in silico analysis (ie, using computer simulation) that is easily accessible to the practicing clinician without need for further laboratory analysis, which can potentially serve as a guide in therapeutic decisions based on poorly characterized tumor mutations. An example of this model is given wherein poorly characterized KIT, PDGFRB, and ERBB2 mutations were discovered in a patient with treatment-refractory metastatic transitional cell carcinoma of the renal pelvis. The KIT and PDGFRB mutations were predicted to be pathogenic using in silico analysis, whereas the ERBB2 mutation was predicted to be benign. Based on these findings, the patient was treated with pazopanib and achieved a partial response that lasted for 7.5 months. We propose that in silico analysis be explored as a potential means to further characterize genetic abnormalities found by tumor profiling assays, such as next-generation sequencing.
Nikolai A. Podoltsev, Mengxin Zhu, Amer M. Zeidan, Rong Wang, Xiaoyi Wang, Amy J. Davidoff, Scott F. Huntington, Smith Giri, Steven D. Gore and Xiaomei Ma
Background: Current guidelines recommend hydroxyurea (HU) as frontline therapy for patients with high-risk essential thrombocythemia (ET) to prevent thrombosis. However, little is known about the impact of HU on thrombosis or survival among these patients in the real-world setting. Patients and Methods: A retrospective cohort study was conducted of older adults (aged ≥66 years) diagnosed with ET from 2007 through 2013 using the linked SEER-Medicare database. Multivariable Cox proportional hazards regression models were used to assess the effect of HU on overall survival, and multivariable competing risk models were used to assess the effect of HU on the occurrence of thrombotic events. Results: Of 1,010 patients, 745 (73.8%) received HU. Treatment with HU was associated with a significantly lower risk of death (hazard ratio [HR], 0.52; 95% CI, 0.43–0.64; P<.01). Every 10% increase in HU proportion of days covered was associated with a 12% decreased risk of death (HR, 0.88; 95% CI, 0.86–0.91; P<.01). Compared with nonusers, HU users also had a significantly lower risk of thrombotic events (HR, 0.51; 95% CI, 0.41–0.64; P<.01). Conclusions: Although underused in our study population, HU was associated with a reduced incidence of thrombotic events and improved overall survival in older patients with ET.
Scott F. Huntington, Jessica R. Hoag, Rong Wang, Amer M. Zeidan, Smith Giri, Steven D. Gore, Xiaomei Ma, Cary P. Gross and Amy J. Davidoff
Background: Provider experience, or clinical volume, is associated with improved outcomes in many complex healthcare settings. Despite increased complexity of anticancer therapies, studies evaluating physician-level experience and cancer treatment outcomes are lacking. Methods: A population-based study was conducted of older adults (aged ≥66 years) diagnosed with B-cell non-Hodgkin’s lymphoma in 2004 through 2011 using SEER-Medicare data. Analysis focused on outcomes in patients receiving rituximab, the first approved monoclonal anticancer immunotherapy. We hypothesized that lower physician experience using rituximab and managing its infusion-related reactions would be associated with early treatment discontinuation. A 12-month look-back from each initiation of rituximab was used to categorize physician volume (0, 1–2, or ≥3 initiations per year). Modified Poisson regression was used to account for provider-level correlation and estimated relative risk (RR) of early rituximab discontinuation (<3 cycles within 180 days of rituximab initiation). Cox proportional hazards were used to measure the impact of rituximab discontinuation on survival. Results: Among 15,110 patients who initiated rituximab with 2,684 physicians, 7.6% experienced early rituximab discontinuation. Approximately one-fourth of patients (26.1%) initiated rituximab with a physician who had no rituximab initiations during the preceding 12 months. Compared with patients treated by physicians who had ≥3 rituximab initiations in the prior year, those treated by physicians without initiations were 57% more likely to experience early discontinuation (adjusted RR [aRR], 1.57; 95% CI, 1.35–1.82; P<.001 for 0 vs ≥3, and aRR, 1.19; 95% CI, 1.03–1.37; P=.02 for 1–2 vs ≥3). Additionally, rituximab discontinuation was associated with higher risk of death (adjusted hazard ratio, 1.39; 95% CI, 1.28–1.52; P<.001). Conclusions: Lower oncologist experience with rituximab was associated with increased risk of early rituximab discontinuation in Medicare beneficiaries with non-Hodgkin’s lymphoma. Physician-level volume may be an important factor in providing high-quality cancer care in the modern era.