Hogan, William J.

e18091 Background: Allogeneic HCT is a potentially curative option for certain patients with AML. However, in-hospital outcomes and cost haven't been described. We use the NIS, a nationally weighted sample of hospital discharges in the US, to examine these outcomes. Methods: Years 2002-2013 of the NIS were queried for adults with a primary diagnosis of AML undergoing HCT. Mortality, length of stay, hospital charges, and complications were analyzed and predictors of increased charges and mortality were determined with multivariate regression analysis. Results: From 2002-2013 19,965 adults with AML were admitted for HCT. Donor sources included peripheral blood stem cells (PBSCTs) (79%); bone marrow (BMTs) (15%); umbilical cord blood (6%). In hospital mortality was 8%. Major complications included stomatitis (36%), total parenteral nutrition (TPN) (17%), neutropenic fever (14%), bacteremia (12%), mechanical ventilation (6%), and dialysis (3%). Median charges per hospitalization increased (p<0.01) from $161,894 (2002) to $324,765 (2013); median length of stay (27 days) remained stable over time. Multivariable regressions are depicted (Table). Umbilical cord blood transplants were associated with increased mortality (OR 2.25, p<0.01) and charges ($69,105, p<0.01) relative to PBSCTs. Conclusions: This study demonstrates increasing cost of BMT on a national level as well as increased cost and mortality with umbilical cord transplants. [Table: see text]

AbstractTrabectedin is an FDA‐approved DNA minor groove binder that has activity against translocation‐associated sarcomas. Lurbinectedin is a next‐generation minor groove binder with preclinical activity against myeloid leukemia cells. A dose‐finding phase 1 clinical trial was performed in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) with further assessment of safety and tolerability. Forty‐two patients with relapsed/refractory AML/MDS received lurbinectedin administered as a 1‐hour intravenous infusion in a 3 + 3 study design. Two dosing schedules were used: 3.5, 5, 7, or 6 mg on days 1 and 8 or 2, 3, 1, or 1.5 mg for 3 consecutive days on days 1 to 3. Three patients experienced dose‐limiting toxicities of rhabdomyolysis (grade 4), hyperbilirubinemia (grade 3), and oral herpes (grade 3) with the day 1 and 8 schedule. Otherwise, adverse events mainly consisted of gastrointestinal manifestations (n = 11), febrile neutropenia/infections (n = 4), pulmonary toxicity (n = 2), and renal failure (n = 2). The most common laboratory abnormalities observed were an increase in creatinine (93%) and anemia, neutropenia, and thrombocytopenia (100%). Overall, 33 of 42 patients (79%) had reduction in blasts in peripheral blood or bone marrow. One patient achieved a partial response and 2 patients a morphologic leukemia‐free state. Most (n = 30, 71%) were discontinued due to progressive disease. Early deaths occurred from disease‐related causes that were not attributable to lurbinectedin. Four patients with a chromosome 11q21‐23 abnormality had significantly greater bone marrow blast reduction than those without such abnormality, with decrease of 31 ± 14% (n = 4) vs 8 ± 8% (n = 16), respectively (P = .04). Overall, lurbinectedin was safe and tolerated using the schedules and dose levels tested. While no sustained remissions were observed, single‐agent lurbinectedin was transiently leukemia suppressive for some patients.

Key PointsHigh-circulating AREG (≥33 pg/mL) reclassifies additional patients into HR categories and further refines the Minnesota aGVHD risk score. Patients with aGVHD and AREG ≥33 pg/mL have lower rates of steroid response, higher NRM, and poorer OS.

SummaryThe optimal duration of induction therapy (IT) in transplant‐eligible multiple myeloma (MM) patients in not well defined, resulting in a wide variation in clinical practice. The objective of our study was to determine whether the duration of IT in patients undergoing upfront autologous stem cell transplantation (ASCT) has an impact on progression‐free survival (PFS) in the era of proteasome inhibitors and immunomodulatory drugs. A total of 596 patients who underwent ASCT at Mayo Clinic between 2007 and 2014 were included. The patients were divided into two cohorts based on the duration of IT: IT ≤ 4 and IT > 4 months. At a median follow‐up of 54·5 months from ASCT, the median PFS in the IT ≤ 4 group was 28 months [95% confidence interval (CI), 25–33], compared to 26 months in the IT > 4 group (95% CI, 24–31) [P = 0·605]. There was no significant difference in overall survival (OS) in the two groups (P = 0·904). The lack of impact of IT duration on PFS and OS was consistent in subgroups with high‐risk features at diagnosis (International Staging System III or high‐risk cytogenetics) and different depths of pre‐transplant response [≥very good partial response (VGPR) and <VGPR]. In conclusion, prolonging the duration of IT beyond 4 months does not impact survival in patients with newly diagnosed MM who complete a single line of IT followed by consolidation with ASCT.