Results of a UK National Cancer Research Institute Phase II study of brentuximab vedotin using a response-adapted design in the first-line treatment of patients with classical Hodgkin lymphoma unsuitable for chemotherapy due to age, frailty or comorbidity (BREVITY).

Standard treatment for classical Hodgkin lymphoma (cHL) is poorly tolerated in older patients and results disappointing. We assessed safety and efficacy of brentuximab vedotin (BV), in previously untreated patients with cHL unfit for standard treatment due to age, frailty or comorbidity. The primary outcome was complete metabolic response (CMR) by positron emission tomography/computed tomography after four BV cycles (PET4). The secondary outcomes included progression-free survival (PFS), overall survival (OS), and toxicity. In all, 35 patients with a median age of 77 years and median total Cumulative Illness Rating Scale for Geriatrics (CIRS-G) score of 6 were evaluable for toxicity and 31 for response. A median of four cycles were given (range one-16). In all, 14 patients required dose reduction due to toxicity and 11 patients stopped treatment due to adverse events (AEs). A total of 716 AEs were reported, of which 626 (88%) were Grade 1/2 and 27 (77%) patients had at least one AE Grade ≥3. At PET4, CMR was 25·8% [95% confidence interval (CI) 13·7-42.2%] and objective response rate 83·9% (95% CI 63·7-90·8%). Median PFS was 7·3 months (95% CI 5·2-9·0), and OS 19·5 months. Our results suggest that BV monotherapy is tolerable but suboptimal in the front-line therapy of elderly or comorbid patients with cHL. Combining BV with other agents may be more effective. Trial Registration: Clinicaltrials.gov identifier: NCT02567851.

Coagulation status and complications of pregnancy.

INTRODUCTION: There is much interest in the relationship between coagulation status and complications of pregnancy. The thrombelastograph (TEG) has been proposed as a useful, inexpensive tool to screen for patients with hypercoagulable states. MATERIALS AND METHODS: We investigated 588 unselected pregnant women at booking, obtaining blood samples for TEG and thrombophilia investigation. Pregnancy outcome data was recorded. RESULTS: We found significant correlations between TEG parameters and the Prothrombin time (PT) and Activated Partial Thromboplastin time (APTT) (p<0.01) and with plasma Antithrombin level (p<0.01). There was no correlation between TEG and other thrombophilic defects (protein C, protein S, Factor V Leiden mutation, Prothrombin G20210A mutation, MTHFR C677T mutation and Lupus Anticoagulant). There was a significant association of TEG parameters with mid-trimester loss (MTL) but not with other adverse pregnancy outcomes. CONCLUSIONS: The correlation between TEG and PT, APTT and antithrombin level supports its value in providing a global measure of haemostasis. Coagulation status at booking is associated with increased risk of MTL but not with complications occurring later in pregnancy.