Quality of life in advanced-stage, asymptomatic, non-bulky follicular lymphoma treated with rituximab shows significant improvement compared with watchful-waiting.

Traditionally, patients with asymptomatic, advanced-stage follicular lymphoma were managed with a watchful-waiting approach until disease progression. The 'Watch and Wait' Phase-3 randomised international trial examined whether rituximab could delay the need for treatment and the effect on quality of life (QoL). In this article, we present the long-term results of the QoL aspect of the trial.

PembroWM: A phase II trial to investigate the safety and efficacy of rituximab and pembrolizumab in relapsed/refractory Waldenström's Macroglobulinaemia.

The optimal therapeutic approach for relapsed/refractory (R/R) Waldenström's Macroglobulinaemia (WM) has not been clearly defined, especially after treatment with chemoimmunotherapy (CIT) and covalent Bruton's tyrosine kinase inhibitors (cBTKi). The PembroWM trial is a multi-centre, phase II, single-arm study assessing the safety, tolerability and efficacy of rituximab with pembrolizumab in R/R WM patients who had received at least one prior line of treatment, with all having relapsed post-CIT and most also exposed to cBTKi. A total of 17 patients were enrolled, with a median age of 70, and median of three prior lines of therapy with 15 either refractory or intolerant of a cBTKi.

A Randomised Phase II Trial of Hippocampal Sparing Versus Conventional Whole Brain Radiotherapy After Surgical Resection or Radiosurgery in Favourable Prognosis Patients With 1-10 Brain Metastases.

Aims: To assess in patients with 1-10 brain metastases, each of which has been treated by neurosurgery or stereotactic radiosurgery, whether hippocampal sparing whole brain radiotherapy (HS-WBRT) better spares neurocognitive function (NCF) than standard WBRT. Further, to assess whether a phase III randomised trial of HS-WBRT would be feasible in the UK.

Materials And Methods: A multicentre, randomised, open label phase II trial was undertaken, randomising patients to 30Gy in 10 fractions of WBRT or HS-WBRT.

Long-term outcomes by bone marrow B-cell depletion from the R2W trial of bortezomib with cyclophosphamide and rituximab in Waldenstrőm macroglobulinaemia.

There remains a lack of consensus as to the most appropriate primary therapy in Waldenstrőm macroglobulinemia (WM). We evaluated a novel bortezomib-based combination and developed a sensitive WM-specific flow cytometry assay (limit of detection 0.004% of leucocytes) to assess bone marrow (BM) response.

Relapse patterns in early-PET negative, limited-stage Hodgkin lymphoma (HL) after ABVD with or without radiotherapy-a joint analysis of EORTC/LYSA/FIL H10 and NCRI RAPID trials.

In the H10 and RAPID randomised trials, chemotherapy+radiotherapy (combined modalities treatment, CMT) was compared with chemotherapy (C) in limited-stage Hodgkin lymphoma (HL), with negative early positron emission tomography (ePETneg). We analysed patterns of relapses in the H10 trial, validated findings in the RAPID trial and performed a combined analysis stratified by trial. The impact of radiotherapy (RT) on risk of relapse was studied using adjusted Cox models, with time-varying effects.

In-vivo T-cell depleted reduced-intensity conditioned allogeneic haematopoietic stem-cell transplantation for patients with acute lymphoblastic leukaemia in first remission: results from the prospective, single-arm evaluation of the UKALL14 trial.

Background: The outcome of chemotherapy in patients older than 40 years with acute lymphoblastic leukaemia is poor and myeloablative allogeneic haematopoietic stem-cell transplantation (HSCT) has a high transplant-related mortality (TRM) in this age cohort. The aim of this study was to assess the activity and safety of reduced-intensity conditioned allogeneic HSCT in this patient population.

Methods: This was a single-arm, prospective study within the UKALL14 trial done in 46 centres in the UK, which recruited patients to the transplantation substudy.

Addition of four doses of rituximab to standard induction chemotherapy in adult patients with precursor B-cell acute lymphoblastic leukaemia (UKALL14): a phase 3, multicentre, randomised controlled trial.

Background: Treatment for adults with acute lymphoblastic leukaemia requires improvement. UKALL14 was a UK National Cancer Research Institute Adult ALL group study that aimed to determine the benefit of adding the anti-CD20 monoclonal antibody, rituximab, to the therapy of adults with de novo B-precursor acute lymphoblastic leukaemia.

Methods: This was an investigator-initiated, phase 3, randomised controlled trial done in all UK National Health Service Centres treating patients with acute lymphoblastic leukaemia (65 centres).

Primary graft failure, but not relapse, may be identified by early chimerism following double cord blood unit transplantation.

Umbilical cord blood transplantation (UCBT) has increased access to potentially curative therapy for patients with life-threatening disorders of the bone marrow and immune system. The introduction of reduced intensity conditioning (RIC) regimens and double umbilical cord unit infusions (DUCBT) has broadened the applicability of UCBT to more frail or larger recipients. The kinetics of chimerism after RIC DUCBT and their clinical utility are poorly understood.

Prognostic impact of chromosomal abnormalities and copy number alterations in adult B-cell precursor acute lymphoblastic leukaemia: a UKALL14 study.

Chromosomal abnormalities are established prognostic markers in adult ALL. We assessed the prognostic impact of established chromosomal abnormalities and key copy number alterations (CNA) among 652 patients with B-cell precursor ALL treated on a modern MRD driven protocol. Patients with KMT2A-AFF1, complex karyotype (CK) and low hypodiploidy/near-triploidy (HoTr) had high relapse rates 50%, 60% & 53% and correspondingly poor survival.

IKZF1 alterations are not associated with outcome in 498 adults with B-precursor ALL enrolled in the UKALL14 trial.

IKZF1 deletions (ΔIKZF1) are commonly detected in B-precursor acute lymphoblastic leukemia (ALL; B-ALL) and are widely assumed to have a significant impact on outcome. We compared the ability of multiplex ligand-dependent probe amplification (MLPA) and polymerase chain reaction (PCR) to detect ΔIKZF1 and to determine the impact on event-free survival of patients with precursor B-ALL aged 23 to 65 years recruited to the completed trial UKALL14 (ISRCTN 66541317). From 655 recruits with BCR-ABL1+ and BCR-ABL1- B-ALL, all available diagnostic DNA samples (76% of the recruited population) were screened by multiplex end point PCR covering 4 deletions: dominant-negative (DN) Δ4-7 or the loss of function Δ2-7, Δ4-8, and Δ2-8 (n = 498), MLPA (n = 436), or by both (n = 420).

Durable Responses and Low Toxicity After Fast Off-Rate CD19 Chimeric Antigen Receptor-T Therapy in Adults With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia.

Purpose: Prognosis for adult B-cell acute lymphoblastic leukemia (B-ALL) is poor, and there are currently no licensed CD19 chimeric antigen receptor (CAR) therapeutics. We developed a novel second-generation CD19-CAR (CAT19-41BB-Z) with a fast off rate, designed for more physiologic T-cell activation to reduce toxicity and improve engraftment. We describe the multicenter phase I ALLCAR19 (NCT02935257) study of autologous CAT19-41BB-Z CAR T cells (AUTO1) in relapsed or refractory (r/r) adult B-ALL.

Predicted Risks of Cardiovascular Disease Following Chemotherapy and Radiotherapy in the UK NCRI RAPID Trial of Positron Emission Tomography-Directed Therapy for Early-Stage Hodgkin Lymphoma.

Purpose: The contemporary management of early-stage Hodgkin lymphoma (ES-HL) involves balancing the risk of late adverse effects of radiotherapy against the increased risk of relapse if radiotherapy is omitted. This study provides information on the risk of radiation-related cardiovascular disease to help personalize the delivery of radiotherapy in ES-HL.

Methods: We predicted 30-year absolute cardiovascular risk from chemotherapy and involved field radiotherapy in patients who were positron emission tomography (PET)-negative following three cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy within a UK randomized trial of PET-directed therapy for ES-HL.

An Evaluation of the Tolerability and Feasibility of Combining 5-Amino-Levulinic Acid (5-ALA) with BCNU Wafers in the Surgical Management of Primary Glioblastoma.

Glioblastoma (GBM) is the commonest primary malignant brain tumour in adults and effective treatment options are limited. Combining local chemotherapy with enhanced surgical resection using 5-aminolevulinic acid (5-ALA) could improve outcomes. Here we assess the safety and feasibility of combining BCNU wafers with 5-ALA-guided surgery.

Thrombotic microangiopathy in untreated myeloma patients receiving carfilzomib, cyclophosphamide and dexamethasone on the CARDAMON study.

Proteasome inhibitors have been associated with thrombotic microangiopathy (TMA) - a group of disorders characterised by occlusive microvascular thrombosis causing microangiopathic haemolytic anaemia, thrombocytopenia and end-organ damage. To date, carfilzomib-associated TMA has predominantly been described in relapsed/refractory myeloma patients. We report eight patients with newly diagnosed myeloma who experienced TMA events while receiving carfilzomib on the phase II CARDAMON trial.

4 Gy versus 24 Gy radiotherapy for follicular and marginal zone lymphoma (FoRT): long-term follow-up of a multicentre, randomised, phase 3, non-inferiority trial.

Background: The optimal radiotherapy dose for indolent non-Hodgkin lymphoma is uncertain. We aimed to compare 24 Gy in 12 fractions (representing the standard of care) with 4 Gy in two fractions (low-dose radiation).

Methods: FoRT (Follicular Radiotherapy Trial) is a randomised, multicentre, phase 3, non-inferiority trial at 43 study centres in the UK.

Hydroxychloroquine and short-course radiotherapy in elderly patients with newly diagnosed high-grade glioma: a randomized phase II trial.

Background: Effective treatment for patients at least 70 years with newly diagnosed glioblastoma remains challenging and alternatives to conventional cytotoxics are appealing. Autophagy inhibition has shown promising efficacy and safety in small studies of glioblastoma and other cancers.

Methods: We conducted a randomized phase II trial to compare radiotherapy with or without hydroxychloroquine (2:1 allocation).

FDG-PET/CT after two cycles of R-CHOP in DLBCL predicts complete remission but has limited value in identifying patients with poor outcome - final result of a UK National Cancer Research Institute prospective study.

The UK National Cancer Research Institute initiated a prospective study (UKCRN-ID 1760) to assess the prognostic value of early fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) in diffuse large B-cell lymphoma (DLBCL). In total, 189 patients with DLBCL treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) had baseline and post-cycle-2 PET (PET2) within a quality assurance framework. Treatment decisions were based on CT; PET2 was archived for central blinded reporting after treatment completion.