• PET-CT for staging & early response: results from 'Response Adapted Therapy in Advanced Hodgkin Lymphoma' (RATHL) (CRUK/07/033).

      Barrington, S; Kirkwood, A; Franceschetto, A; Fulham, M; Roberts, T; Almquist, H; Brun, E; Hjorthaug, K; Viney, Z; Pike, L; et al. (2016-01-08)
      International guidelines recommend PET-CT should replace CT in Hodgkin Lymphoma (HL). The aims of this study were to i) compare PET-CT with CT for staging and ii) measure agreement between expert and local readers, using a five-point scale (Deauville criteria), to adapt treatment in a clinical trial 'Response Adapted Therapy in Advanced Hodgkin Lymphoma' (RATHL) www.cancer.gov/clinicaltrials, reference NCT00678327. Patients were staged for the trial using clinical assessment, CT and bone marrow biopsy (RATHL stage). PET-CT was performed at baseline (PET0) and after 2 chemotherapy cycles (PET2) in a response-adapted design. PET-CT was reported centrally by experts at 5 national core labs. Local readers optionally scored PET2 scans. The RATHL and PET-CT stages were compared. Agreement amongst experts and between expert and local readers was measured. RATHL and PET0 stage were concordant in 938 (80%) patients. PET-CT upstaged 159 (14%) and downstaged 74 (6%) patients. Upstaging by extranodal disease in bone marrow (92), lung (11) or multiple sites (12) on PET-CT accounted for most discrepancies. Follow-up of discrepant findings confirmed the PET characterisation of lesions in the vast majority. Five patients were upstaged by marrow biopsy; 7 by contrast-enhanced CT in bowel and/or liver or spleen. PET2 agreement amongst experts (140 scans) with kappa (95% CI) of 0.84 (0.76 - 0.91) was very good and between experts and local readers (300 scans) at 0.77 (0.68-0.86) was good. These results confirm PET-CT as the modern standard for staging HL and that response assessment using Deauville criteria is robust enabling translation of RATHL results into clinical practice.
    • Phase II trial of zanolimumab (HuMax-CD4) in relapsed or refractory non-cutaneous peripheral T cell lymphoma.

      D'Amore, F; Radford, John A; Relander, T; Jerkeman, M; Tilly, H; Osterborg, A; Morschhauser, F; Gramatzki, M; Dreyling, M; Bang, B; et al. (2010-09)
      The efficacy and safety of zanolimumab (HuMax-CD4) in patients with relapsed or refractory peripheral T Cell lymphoma (PTCL) was evaluated. Twenty-one adult patients with relapsed or refractory CD4(+) PTCL of non-cutaneous type (angioimmunoblastic T cell lymphoma (AITL) n = 9, PTCL-not otherwise specified (NOS) n = 7, anaplastic large cell lymphoma (ALCL) n = 4 and enteropathy type T cell lymphoma n = 1) were treated in a single-arm multi-centre study, with weekly intravenous infusions of zanolimumab 980 mg for 12 weeks. Median age was 69 years (range 26-85). Seventeen of the patients had advanced stage disease (Ann Arbor stages III-IV). Objective tumour responses were obtained in 24% of the patients with two complete responses unconfirmed (CRu) and three partial responses (PR). One of the CRus lasted more than 252 d. Responses were obtained in different PTCL entities: AITL (n = 3), ALCL (n = 1) and PTCL-NOS (n = 1). In general, the trial drug was well tolerated with no major toxicity. Zanolimumab at a dose of 980 mg weekly demonstrated clinical activity and an acceptable safety profile in this poor-prognosis patient population, suggesting that the potential benefit combining zanolimumab with standard chemotherapy in the treatment of PTCL should be investigated.