IMPORTANCECheckpoint inhibitors targeting programmed cell death 1 or its ligand (PD-L1) as monotherapies or in combination with anti-cytotoxic T-lymphocyte-associated antigen 4 have shown clinical activity in patients with metastatic non-small cell lung cancer.OBJECTIVE To compare durvalumab, with or without tremelimumab, with chemotherapy as a first-line treatment for patients with metastatic non-small cell lung cancer. DESIGN, SETTING, AND PARTICIPANTSThis open-label, phase 3 randomized clinical trial (MYSTIC) was conducted at 203 cancer treatment centers in 17 countries. Patients with treatment-naive, metastatic non-small cell lung cancer who had no sensitizing EGFR or ALK genetic alterations were randomized to receive treatment with durvalumab, durvalumab plus tremelimumab, or chemotherapy. Data were collected from July 21, 2015, to October 30, 2018.INTERVENTIONS Patients were randomized (1:1:1) to receive treatment with durvalumab (20 mg/kg every 4 weeks), durvalumab (20 mg/kg every 4 weeks) plus tremelimumab (1 mg/kg every 4 weeks, up to 4 doses), or platinum-based doublet chemotherapy. MAIN OUTCOMES AND MEASURESThe primary end points, assessed in patients with Ն25% of tumor cells expressing PD-L1, were overall survival (OS) for durvalumab vs chemotherapy, and OS and progression-free survival (PFS) for durvalumab plus tremelimumab vs chemotherapy. Analysis of blood tumor mutational burden (bTMB) was exploratory.

Adult patients with acute lymphoblastic leukemia (ALL) who are stratified into the standard-risk (SR) group due to the absence of adverse prognostic factors relapse in 40% to 55% of the cases. To identify complementary markers suitable for further treatment stratification in SR ALL, we evaluated the predictive value of minimal residual disease (MRD) and prospectively monitored MRD in 196 strictly defined SR ALL patients at up to 9 time points in the first year of treatment by quantitative polymerase chain reaction (PCR). Frequency of MRD positivity decreased from 88% during early induction to 13% at week 52. MRD was predictive for relapse at various follow-up time points. Combined MRD information from different time points allowed definition of 3 risk groups (P < .001): 10% of patients with a rapid MRD decline to lower than 10 ؊4 or below detection limit at day 11 and day 24 were classified as low risk and had a 3-year relapse rate (RR) of 0%. A subset of 23% with an MRD of 10 ؊4 or higher until week 16 formed the high-risk group, with a 3-year RR of 94% (95% confidence interval [CI] 83%-100%). The remaining patients whose RR was 47% (31%- 63% IntroductionInvestigation of minimal residual disease (MRD) has been proven to be a valuable tool for predicting outcome in childhood acute lymphoblastic leukemia (ALL). [1][2][3][4][5] In contrast, only a few studies have focused on adult ALL, and they were based mostly on patients with heterogeneous risk profiles and different kinds and intensities of treatment. [6][7][8] However, monitoring homogeneous patient cohorts at different time points during therapy might provide additional insight into the nature and clinical relevance of MRD kinetics in adult ALL, which is particularly relevant for the large population of standard-risk (SR) patients without conventional risk factors. Relapses in this patient group occur in about 40% to 55% of cases and cannot be predicted by any known conventional risk factor. [9][10][11] In a number of clinical studies this led to a policy of stem cell transplantation (SCT) in first remission, 12-14 causing overtreatment and additional expenses for those patients who are cured by conventional chemotherapy alone. Therefore, definition of prognostic factors allowing discrimination of SR patients with poor outcome after standard chemotherapy from those with a favorable prognosis is highly warranted. Currently, the most widely used techniques to detect and quantify residual disease in patients with ALL are multiparameter immunophenotypic evaluation of aberrant protein expression 2,3,8 and clone-specific polymerase chain reaction (PCR) amplification of immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements. 1,4,5 Such molecular targets can be identified in more than 90% of patients with ALL by the use of various PCR primer sets. Besides its large applicability and high sensitivity, a main advantage of PCR-based assays is the use of DNA as a stable and easy conveyable specimen, which is particularly relevant in large multicenter studies....

In this study, sorafenib resulted in similar PFS as IFN-alpha-2a in patients with untreated RCC. However, sorafenib-treated patients experienced greater rates of tumor size reduction, better QOL, and improved tolerability. Both dose escalation of sorafenib after progression and a switch to sorafenib after progression on IFN-alpha-2a resulted in clinical benefit.