Purpose: Blinatumomab is a CD19/CD3 BiTE (bispecific T-cell engager) antibody construct for the treatment of Philadelphia chromosome–negative acute B-lymphoblastic leukemia. We evaluated blinatumomab in relapsed/refractory B-cell non-Hodgkin lymphoma (NHL).Patients and Methods: This 3 + 3 design, phase I dose-escalation study determined adverse events and the maximum tolerated dose (MTD) of continuous intravenous infusion blinatumomab in patients with relapsed/refractory NHL. Blinatumomab was administered over 4 or 8 weeks at seven different dose levels (0.5 to 90 μg/m²/day). End points were incidence of adverse events, pharmacokinetics, pharmacodynamics, and overall response rate.Results: Between 2004 and 2011, 76 heavily pretreated patients with relapsed/refractory NHL, who included 14 with diffuse large B-cell lymphoma, were enrolled; 42 received treatment in the formal dose-escalation phase. Neurologic events were dose limiting, and 60 μg/m²/day was established as the MTD. Thirty-four additional patients were recruited to evaluate antilymphoma activity and strategies for mitigating neurologic events at a prespecified MTD. Stepwise dosing (5 to 60 μg/m²/day) plus pentosan polysulfate SP54 (n = 3) resulted in no treatment discontinuations; single-step (n = 5) and double-step (n = 24) dosing entailed two and seven treatment discontinuations due to neurologic events, respectively. Grade 3 neurologic events occurred in 22% of patients (no grade 4/5). Among patients treated at 60 μg/m²/day (target dose; n = 35), the overall response rate was 69% across NHL subtypes and 55% for diffuse large B-cell lymphoma (n = 11); median response duration was 404 days (95% CI, 207 to 1,129 days).Conclusion: In this phase I study of relapsed/refractory NHL, continuous infusion with CD19-targeted immunotherapy blinatumomab at various doses and schedules was feasible, with an MTD of 60 μg/m²/day. Single-agent blinatumomab showed antilymphoma activity.

(1) Background: molecular tumor boards (MTBs) are crucial instruments for discussing and allocating targeted therapies to suitable cancer patients based on genetic findings. Currently, limited evidence is available regarding the regional impact and the outreach component of MTBs; (2) Methods: we analyzed MTB patient data from four neighboring Bavarian tertiary care oncology centers in Würzburg, Erlangen, Regensburg, and Augsburg, together constituting the WERA Alliance. Absolute patient numbers and regional distribution across the WERA-wide catchment area were weighted with local population densities; (3) Results: the highest MTB patient numbers were found close to the four cancer centers. However, peaks in absolute patient numbers were also detected in more distant and rural areas. Moreover, weighting absolute numbers with local population density allowed for identifying so-called white spots—regions within our catchment that were relatively underrepresented in WERA MTBs; (4) Conclusions: investigating patient data from four neighboring cancer centers, we comprehensively assessed the regional impact of our MTBs. The results confirmed the success of existing collaborative structures with our regional partners. Additionally, our results help identifying potential white spots in providing precision oncology and help establishing a joint WERA-wide outreach strategy.

PurposeCardiotoxic adverse events (AE) are challenging in the field of oncologic therapy. Age-related prevalence of cardiovascular disease and cancer itself may contribute to an increased risk of cardiac morbidity. Cardiac dysfunction impacts cardiac morbidity, survival and quality of life in cancer patients. This study established a cardio-oncological monitoring for the early detection of cardiovascular complications during experimental anti-tumour therapy. MethodsNinety patients referred to experimental anti-tumour therapy underwent prospective monitoring including repeat-electrocardiogram (ECG), echocardiography with speckle tracking imaging (STI), and determination of cardiac biomarkers. Changes in cardiac function were evaluated according to the Common Terminology Criteria of Adverse Events (CTCAE Version 4.03). ResultsConventional ECG, high-sensitive troponin T, echocardiography including STI-analysis, and 24-hour Holter ECG were identified as relevant diagnostic tools. Early signs of cardiotoxicity appeared within the first 3 months after initiating anti-tumour therapy. Most frequent AEs were mitral valve disease (22%), diastolic dysfunction (15.7%), sinus tachycardia (13.8%), and increased hs-TnT (13.8%). ConclusionProspective cardiac monitoring allowed early detection of cardiac dysfunction during experimental anti-tumour therapy. A multi­disciplinary work-up and decision-making during cancer treatment is warranted to foster a deeper understanding of the underlying mechanisms of cardiac AEs and particularly to early detect and counteract cardiotoxicity.