Clinical development of cell therapies for cancer: The regulators' perspective.

Novel cell therapies for haematological malignancies and solid tumours address pressing clinical need while offering potentially paradigm shifts in efficacy. However, innovative development risks outflanking information on statutory frameworks, regulatory guidelines and their working application. Meeting this challenge, regulators offer wide-ranging expertise and experience in confidential scientific and regulatory advice. We advocate early incorporation of regulatory perspectives to support strategic development of clinical programmes. We examine critical issues and key advances in clinical oncology trials to highlight practical approaches to optimising the clinical development of cell therapies. We recommend early consideration of collaborative networks, early-access schemes, reducing bias in single-arm trials, adaptive trials, clinical end-points supporting risk/benefit and cost/benefit analyses, companion diagnostics, real-world data and common technical issues. This symbiotic approach between developers and regulators should reduce development risk, safely expedite marketing authorisation, and promote early, wider availability of potentially transformative cell therapies for cancer.

The outcomes of lung transplantation in patients with bronchiectasis and antibody deficiency.

BACKGROUND: Lung transplantation is an established treatment for end-stage bronchiectasis. A proportion of patients with bronchiectasis have an associated antibody deficiency. This group benefits from immunoglobulin replacement therapy, but the outcome of lung transplantation is not known. METHODS: We conducted a retrospective observational study of all who received a transplant for bronchiectasis at our unit. We compared the survival after transplant, number of infective and rejection episodes, and the change in forced expiratory volume in 1 second (FEV1). RESULTS: Five of the 37 patients identified with bronchiectasis had an antibody deficiency that required immunoglobulin replacement therapy. Actuarial survival was similar in the 2 groups, being 81% at 12 months in the Bronchiectasis Group and 80% in the Antibody Deficiency Group. The FEV1 at 12 months after transplantation was similar in each group, with a predicted mean +/- SD FEV1 of 83.7% +/- 24.2% in those with bronchiectasis and 83.0% +/- 30.4% in those with antibody deficiency as well. The infection and rejection rates in the first year after transplantation were lower in the Antibody Deficiency Group. Infection episodes per 100 patient-days for bronchiectasis alone were 0.90 vs 0.53 and rejection episodes per 100 patient-days were 0.59 vs 0.24. CONCLUSIONS: There was no evidence that transplant recipients with bronchiectasis and antibody deficiency have a worse prognosis than those with bronchiectasis alone.