Pulmonary function testing for fitness assessment in asymptomatic adults with newly diagnosed acute myeloid leukemia

Not available

Phase 2 study of RO4929097, a gamma‐secretase inhibitor, in metastatic melanoma: SWOG 0933

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110565/1/cncr29055.pd

A Phase II Basket Trial of Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors (DART SWOG 1609) in Patients with Nonpancreatic Neuroendocrine Tumors.

PurposeImmune checkpoint blockade has improved outcomes across tumor types; little is known about the efficacy of these agents in rare tumors. We report the results of the (nonpancreatic) neuroendocrine neoplasm cohort of SWOG S1609 dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART).Patients and methodsWe performed a prospective, open-label, multicenter phase II clinical trial of ipilimumab plus nivolumab across multiple rare tumor cohorts, with the (nonpancreatic) neuroendocrine cohort reported here. Response assessment by grade was not prespecified. The primary endpoint was overall response rate [ORR; RECIST v1.1; complete response (CR) and partial response (PR)]; secondary endpoints included progression-free survival (PFS), overall survival (OS), stable disease >6 months, and toxicity.ResultsThirty-two eligible patients received therapy; 18 (56%) had high-grade disease. Most common primary sites were gastrointestinal (47%; N = 15) and lung (19%; N = 6). The overall ORR was 25% [95% confidence interval (CI) 13-64%; CR, 3%, N = 1; PR, 22%, N = 7]. Patients with high-grade neuroendocrine carcinoma had an ORR of 44% (8/18 patients) versus 0% in low/intermediate grade tumors (0/14 patients; P = 0.004). The 6-month PFS was 31% (95% CI, 19%-52%); median OS was 11 months (95% CI, 6-∞). The most common toxicities were hypothyroidism (31%), fatigue (28%), and nausea (28%), with alanine aminotransferase elevation (9%) as the most common grade 3/4 immune-related adverse event, and no grade 5 events.ConclusionsIpilimumab plus nivolumab demonstrated a 44% ORR in patients with nonpancreatic high-grade neuroendocrine carcinoma, with 0% ORR in low/intermediate grade disease

Minimal residual disease prior to allogeneic hematopoietic cell transplantation in acute myeloid leukemia: a meta-analysis

Minimal residual disease prior to allogeneic hematopoietic cell transplantation has been associated with increased risk of relapse and death in patients with acute myeloid leukemia, but detection methodologies and results vary widely. We performed a systematic review and meta-analysis evaluating the prognostic role of minimal residual disease detected by polymerase chain reaction or multiparametric flow cytometry before transplant. We identified 19 articles published between January 2005 and June 2016 and extracted hazard ratios for leukemia-free survival, overall survival, and cumulative incidences of relapse and non-relapse mortality. Pre-transplant minimal residual disease was associated with worse leukemia-free survival (HR=2.76 [1.90-4.00]), overall survival (HR=2.36 [1.73-3.22]), and cumulative incidence of relapse (HR=3.65 [2.53-5.27]), but not non-relapse mortality (HR=1.12 [0.81-1.55]). These associations held regardless of detection method, conditioning intensity, and patient age. Adverse cytogenetics was not an independent risk factor for death or relapse. There was more heterogeneity among studies using flow cytometry-based than WT1 polymerase chain reaction-based detection (I(2)=75.1% vs. <0.1% for leukemia-free survival, 67.8% vs. <0.1% for overall survival, and 22.1% vs. <0.1% for cumulative incidence of relapse). These results demonstrate a strong relationship between pre-transplant minimal residual disease and post-transplant relapse and survival. Outcome heterogeneity among studies using flow-based methods may underscore site-specific methodological differences or differences in test performance and interpretation

Conditioning intensity and peritransplant flow cytometric MRD dynamics in adult AML

In acute myeloid leukemia (AML), measurable residual disease (MRD) before or after allogeneic hematopoietic cell transplantation (HCT) is an established independent indicator of poor outcome. To address how peri-HCT MRD dynamics could refine risk assessment across different conditioning intensities, we analyzed 810 adults transplanted in first or second remission after myeloablative conditioning (MAC; n = 515) or non-MAC (n = 295) who underwent multiparameter flow cytometry–based MRD testing before as well as 20 to 40 days after allografting. Patients without pre- and post-HCT MRD (MRDneg/MRDneg) had the lowest risks of relapse and highest relapse-free survival (RFS) and overall survival (OS). Relative to those patients, outcomes for MRDpos/MRDpos and MRDneg/MRDpos patients were poor regardless of conditioning intensity. Outcomes for MRDpos/MRDneg patients were intermediate. Among 161 patients with MRD before HCT, MRD was cleared more commonly with a MAC (85 of 104; 81.7%) than non-MAC (33 of 57; 57.9%) regimen (P = .002). Although non-MAC regimens were less likely to clear MRD, if they did, the impact on outcome was greater. Thus, there was a significant interaction between conditioning intensity and “MRD conversion” for relapse (P = .020), RFS (P = .002), and OS (P = .001). Similar findings were obtained in the subset of 590 patients receiving HLA-matched allografts. C-statistic values were higher (indicating higher predictive accuracy) for peri-HCT MRD dynamics compared with the isolated use of pre-HCT MRD status or post-HCT MRD status for prediction of relapse, RFS, and OS. Across conditioning intensities, peri-HCT MRD dynamics improve risk assessment over isolated pre- or post-HCT MRD assessments in patients with AML