Scott F. Huntington

Evolution to plasmablastic lymphoma evades CD19-directed chimeric antigen receptor T cells.

A patient with relapsed and refractory chronic lymphocytic leukaemia with Richter transformation was treated with chimeric antigen receptor (CAR)‐modified T cells targeted for CD19 but later relapsed with a clonally related plasmablastic lymphoma. The loss of most routine markers of pre‐plasma cell or B lymphoid differentiation (including CD19) highlights the ability of such mature lymphomas to evade lineage‐specific targeted immunotherapy by differentiating along pathways comparable to their normal cellular counterparts. Molecular genetic evaluation demonstrated multiple independent lines of CD19‐negative disease that eventually evolved in this single patient. Such plasticity represents potential challenges for antigen‐directed CAR‐T cell therapy, while serving as a testament to the selective pressure exerted by these engineered T cells over time.

Cost-Effectiveness Analysis of Routine Surveillance Imaging of Patients With Diffuse Large B-Cell Lymphoma in First Remission

PURPOSE Surveillance imaging of asymptomatic patients with diffuse large B-cell lymphoma (DLBCL) in first remission remains controversial. A decision-analytic Markov model was developed to evaluate the cost-effectiveness of follow-up strategies following first-line immunochemotherapy. PATIENTS AND METHODS Three strategies were compared in 55-year-old patient cohorts: routine clinical follow-up without serial imaging, routine follow-up with biannual computed tomography (CT) scans for 2 years, or routine follow-up with biannual [(18)F]-fluorodeoxyglucose positron emission tomography-computed tomography (PET/CT) for 2 years. The baseline model favored imaging-based strategies by associating asymptomatic imaging-detected relapses with improved clinical outcomes. Lifetime costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated for each surveillance strategy. RESULTS Surveillance strategies utilizing 2 years of routine CT or PET/CT scans were associated with minimal survival benefit when compared with clinical follow-up without routine imaging (life-years gained: CT, 0.03 years; PET/CT, 0.04 years). The benefit of imaging-based follow-up remained small after quality-of-life adjustments (CT, 0.020 QALYs; PET/CT, 0.025 QALYs). Costs associated with imaging-based surveillance strategies are considerable; ICERs for imaging strategies compared with clinical follow-up were

Comparative clinical effectiveness of azacitidine versus decitabine in older patients with myelodysplastic syndromes.

164,960/QALY (95% CI,

Utility of interim and end-of-treatment [18F]-fluorodeoxyglucose positron emission tomography–computed tomography in frontline therapy of patients with diffuse large B-cell lymphoma

116,510 to

Modest improvement in survival of patients with refractory anemia with excess blasts in the hypomethylating agents era in the United States

766,930/QALY) and

Toxicities and outcomes among septuagenarians and octogenarians with diffuse large B-cell lymphoma treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone therapy

168,750/QALY (95% CI,

Myelodysplastic Syndromes and Acute Myeloid Leukemia After Radiotherapy for Prostate Cancer: A Population-Based Study

117,440 to 853,550/QALY) for CT and PET/CT, respectively. Model conclusions were robust and remained stable on one-way and probabilistic sensitivity analyses. CONCLUSION Our cost-effectiveness analysis suggests surveillance imaging of asymptomatic DLBCL patients in remission offers little clinical benefit at substantial economic costs.

R‐CHOP versus dose‐adjusted R‐EPOCH in frontline management of primary mediastinal B‐cell lymphoma: a multi‐centre analysis

The hypomethylating agents (HMAs) azacitidine and decitabine are both approved for treatment of myelodysplastic syndromes (MDS) in the USA. In Europe, decitabine is not approved due to lack of survival advantage in randomized trials. The two drugs have not been compared in clinical trials. We identified patients diagnosed with MDS between 2004 and 2011 from the Surveillance, Epidemiology, and End Results (SEER)‐Medicare linked database in the USA who received ≥ 10 doses of either HMA. We estimated survival from HMA initiation with Kaplan–Meier methods and used multivariate Cox proportional hazards models to adjust for covariates. Analyses controlled for histological subtype and we conducted a subset analysis limited to patients with refractory anaemia with excess blasts (RAEB). In 2025 HMA‐treated patients, median survival was 15 months with no difference in survival based on the HMA received in adjusted analysis (decitabine versus azacitidine, hazard ratio = 1·06, 95% confidence interval: 0·94–1·19, P = 0·37). For RAEB patients (n = 523), median survival was 12 months, with no significant difference based on HMA received. No significant survival difference was found between azacitidine and decitabine in patients with MDS, including RAEB. Importantly, population‐based survival of azacitidine‐treated RAEB patients was substantially shorter than in the AZA‐001 clinical trial (11 versus 24·5 months).

Health Care Use by Older Adults With Acute Myeloid Leukemia at the End of Life

[18F]-fluorodeoxyglucose positron emission tomography–computed tomography (PET/CT) is part of standard pretreatment staging and post-treatment assessment in patients undergoing first-line therapy for diffuse large B-cell lymphoma (DLBCL). While many providers obtain interim PET/CT (I-PET) for DLBCL, the clinical utility of these scans is unclear. We conducted a retrospective study of patients with DLBCL undergoing I-PET during first-line therapy (n = 94). The majority (61%) of patients had at least one negative I-PET and all patients with negative I-PET remained in remission at the end of treatment. I-PET was strongly associated with progression-free survival and remained independent on multivariable modeling (non-complete remission [CR]:CR I-PET, hazard ratio 2.7, p = 0.01). All patients with negative I-PET were in remission at the end of frontline therapy, and end-of-treatment PET/CT offered little clinical utility in this subset. Therefore, I-PET may offer an approach of early clinical predication and obviate the need for end-of-treatment imaging in the majority of patients with DLBCL.

Hypomethylating agent therapy use and survival in older patients with chronic myelomonocytic leukemia in the United States: A large population-based study

Amer M. Zeidan, Rong Wang, Cary P. Gross, Steven D. Gore, Scott F. Huntington, Thomas Prebet , Gregory A. Abel, Amy J. Davidoff and Xiaomei Ma Section of Hematology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA; Cancer Outcomes, Public Policy, and Effectiveness Research (COPPER) Center, Yale University, New Haven, CT, USA; Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, USA; Division of Population Sciences, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Health Policy and Management, Yale School of Public Health, New Haven, CT, USA