Guideline for the first-line management of Classical Hodgkin Lymphoma - A British Society for Haematology guideline.

This guideline was compiled according to the British Society for Haematology (BSH) process at BSH Guidelines Process 2016 (b-s-h.org.uk). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) nomenclature was used to evaluate levels of evidence and to assess the strength of recommendations. The GRADE criteria can be found at http://www.gradeworkinggroup.org. Recommendations are based on a review of the literature using Medline, PubMed/Medline and Cochrane searches beginning from 2013 up to January 2021. The following search terms were used: [Hodgkin lymphoma OR Hodgkin disease] NOT non-Hodgkin; AND [chemotherapy OR radiotherapy]; AND [elderly]; AND [teenage OR adolescent OR young adult]; AND [pregnancy]. Filters were applied to include only publications written in English, studies carried out in humans, clinical conferences, congresses, clinical trials, clinical studies, meta-analyses, multicentre studies and randomised controlled trials. References pre-2013 were taken from the previous version of this guideline.1 Review of the manuscript was performed by the British Society for Haematology (BSH) Guidelines Committee Haematology Oncology Taskforce, the BSH Guidelines Committee and the Haematology Oncology sounding board of BSH.

Advanced Hodgkin lymphoma in the East of England: a 10-year comparative analysis of outcomes for real-world patients treated with ABVD or escalated-BEACOPP, aged less than 60 years, compared with 5-year extended follow-up from the RATHL trial.

Treatment with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) or escalated(e)-BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisolone) remains the international standard of care for advanced-stage classical Hodgkin lymphoma (HL). We performed a retrospective, multicentre analysis of 221 non-trial ("real-world") patients, aged 16-59 years, diagnosed with advanced-stage HL in the Anglia Cancer Network between 2004 and 2014, treated with ABVD or eBEACOPP, and compared outcomes with 1088 patients in the Response-Adjusted Therapy for Advanced Hodgkin Lymphoma (RATHL) trial, aged 18-59 years, with median follow-up of 87.0 and 69.5 months, respectively. Real-world ABVD patients (n=177) had highly similar 5-year progression-free survival (PFS) and overall survival (OS) compared with RATHL (PFS 79.2% vs 81.4%; OS 92.9% vs 95.2%), despite interim positron-emission tomography-computed tomography (PET/CT)-guided dose-escalation being predominantly restricted to trial patients. Real-world eBEACOPP patients (n=44) had superior PFS (95.5%) compared with real-world ABVD (HR 0.20, p=0.027) and RATHL (HR 0.21, p=0.015), and superior OS for higher-risk (international prognostic score ≥3 [IPS 3+]) patients compared with real-world IPS 3+ ABVD (100% vs 84.5%, p=0.045), but not IPS 3+ RATHL patients. Our data support a PFS, but not OS, advantage for patients with advanced-stage HL treated with eBEACOPP compared with ABVD and suggest higher-risk patients may benefit disproportionately from more intensive therapy. However, increased access to effective salvage therapies might minimise any OS benefit from reduced relapse rates after frontline therapy.

Health-related quality of life in the phase III GALLIUM study of obinutuzumab- or rituximab-based chemotherapy in patients with previously untreated advanced follicular lymphoma.

Health-related quality of life was a secondary endpoint in the phase III GALLIUM study in previously untreated patients with follicular lymphoma who were treated with rituximab- or obinutuzumab-chemotherapy. Patients were randomized 1:1 to receive induction therapy with obinutuzumab- or rituximab-chemotherapy and maintenance in responders. Health-related quality of life was assessed using the Functional Assessment of Cancer Treatment-Lymphoma questionnaire, incorporating well-being and lymphoma-specific subscales. Assessments were performed at baseline, and during induction, maintenance, and follow-up (maximum 84 months). Clinically meaningful responses were defined by minimally important difference values. Of 1202 randomized patients (median follow-up 57.4 months), 557/601 (92.7%; obinutuzumab-chemotherapy) and 548/601 (91.2%; rituximab-chemotherapy) completed all Functional Assessment of Cancer Treatment-Lymphoma scales at baseline. Mean baseline health-related quality of life scores were similar between both arms, with all patients having some functional impairment and lymphoma symptoms. Over the course of treatment, mean health-related quality of life remained similar in both arms. Equal proportions of patients in both arms achieved minimally important difference by the Functional Assessment of Cancer Treatment-Lymphoma lymphoma-specific subscale and summary scales throughout induction, maintenance, and follow-up. On each summary scale, ~ 50% of patients in each arm achieved minimally important difference by maintenance month 2. In GALLIUM, similar improvements in health-related quality of life were seen with obinutuzumab- and rituximab-chemotherapy, suggesting that both treatments reduced lymphoma-related symptoms, and treatment-related side effects did not abrogate these improvements in well-being. ClinicalTrials.gov identifier: NCT01332968.

Managing relapsed refractory lymphoma with palliative oral chemotherapy: A multicentre retrospective study.

PEP-C (prednisolone, etoposide, procarbazine and cyclophosphamide) is an orally administered daily chemotherapy regimen used with palliative intent in relapsed refractory lymphoma. To our knowledge, no data on PEP-C have been reported since the original group described the regimen. Here we present a multicentre retrospective cohort reporting our use of PEP-C in 92 patients over an 8-year period. We find that even heavily pretreated lymphoma can respond to PEP-C, particularly low-grade lymphoma (including mantle cell) and lymphoma that was sensitive to the previous line of systemic therapy (chemosensitive). These characteristics may help in the selection of patients likely to derive benefit. The median overall survival of patients with chemosensitive lymphoma treated with PEP-C is 217 days. Within the limitations of a retrospective cohort, we find that PEP-C is well tolerated: the most common toxicity leading to discontinuation is marrow suppression. We suggest that PEP-C should be considered for patients with relapsed refractory lymphoma in two settings: first, where there is no licensed alternative; and second, where the licensed alternative is an intravenous drug and the patient would prefer to choose an oral chemotherapy option.

Treatment and outcome patterns in European patients with Waldenström's macroglobulinaemia: a large, observational, retrospective chart review.

BACKGROUND: Treatment options for Waldenström's macroglobulinaemia are heterogeneous, and no well established treatment standards exist. Although guidelines from the Eighth International Workshop on Waldenstrom's Macroglobulinemia were published in 2016, inconsistent awareness and budget constraints have prevented their widespread implementation, and real-life treatment patterns might differ across health-care systems. We aimed to generate information about treatment and outcome patterns for patients with Waldenström's macroglobulinaemia outside of clinical trials. METHODS: In this large, observational, retrospective chart review, academic and community physicians in ten European countries were invited to retrospectively complete electronic records for patients with symptomatic Waldenström's macroglobulinaemia who had begun treatment after Jan 1, 2000, and before Jan 1, 2014, and had available clinical and biological data. The primary endpoints were reasons for treatment initiation, treatment choices, progression-free survival, and overall survival. We assessed the variables that affected choice of front-line therapy, progression-free survival, and overall survival in multivariate analyses. FINDINGS: Electronic records were reviewed for 454 eligible patients. The most frequent reasons for starting front-line treatment were anaemia (in 328 [72%] patients) and constitutional symptoms (in 264 [58%] patients). Choice of therapy varied between front-line, second-line, and third-line approaches; age; and type of institution. In the front-line setting, 193 (43%) of 454 patients received monotherapy, 164 (36%) received chemoimmunotherapy, and 95 (21%) received other combination regimens (data on front-line treatment were missing for one patient, and another patient received only steroids). After front-line treatment, median progression-free survival was 29 months (95% CI 25-31), median overall survival was not reached (not reached-not reached), and 10-year overall survival was 69% (62-74). In multivariate analyses, patients who were high risk according to the International Prognostic Scoring System for Waldenström Macroglobulinemia had significantly worse progression-free survival and overall survival than did those who were low risk. Additionally, progression-free survival was shortened in patients treated with monotherapy compared with those treated with chemoimmunotherapy or other combination therapies and in those treated at an academic institution compared with those treated in the community. Constitutional symptoms (excluding fatigue) were associated with worsened overall survival. INTERPRETATION: This large observational dataset should inform and help set guidelines, and improve understanding of treatment practices and outcomes, for European patients with Waldenström's macroglobulinaemia. FUNDING: Pharmacyclics LLC (an AbbVie company).

Best practice guidelines for the management of adverse events associated with amphotericin B lipid complex.

IMPORTANCE OF THE FIELD: Amphotericin B lipid complex is a widely used lipid-based formulation of amphotericin B, which has a broad spectrum of activity against a variety of fungal pathogens. It has also been shown to be significantly less nephrotoxic than conventional amphotericin B. However, infusional drug reactions, similar to those seen when using conventional amphotericin B, have been reported in a significant number of patients, so it is important that these are prevented or managed effectively, particularly in light of the changing epidemiology of systemic fungal infections. AREAS COVERED IN THIS REVIEW: This article reviews effective strategies that can be used to reduce the risk of drug delivery reactions associated with amphotericin B lipid complex. Preserving renal function and managing spikes in serum creatinine levels are also discussed. WHAT THE READER WILL GAIN: The aim of this paper is to provide healthcare professionals with clear guidance on the management of adverse events associated with amphotericin B lipid complex. Recommendations are based upon the published evidence and clinical experience from a number of different centres. TAKE HOME MESSAGE: Amphotericin B lipid complex represents a valuable therapeutic option in the treatment of fungal infections but improved strategies for the management of infusion-related adverse events are required.

The current role of amphotericin B lipid complex in managing systemic fungal infections.

BACKGROUND: An increase in the number of immunocompromised patients has led to a rising burden of systemic fungal infections. Historically, conventional amphotericin B has been used to treat these infections due to its broad spectrum of activity. The development of lipid-based amphotericin B agents, such as Abelcet * (ABLC), has allowed clinicians to take advantage of the broad spectrum of activity of amphotericin B while reducing adverse events. As well as this, a number of new antifungal agents have been developed in recent years which have significantly added to the treating physician's antifungal armamentarium. * Abelcet is a registered trade name of Cephalon Ltd, Herts, UK. OBJECTIVES: Review the clinical data that support the use of ABLC and discuss the evidence for its continuing role in the treatment of invasive fungal infections in light of the introduction of newer antifungal agents. METHODS: Published studies were identified by searching the MEDLINE database and the Cochrane Centre for Reviews up to August 2009. The search was conducted using the following key words: Amphotericin, Lipid, Abelcet, AmBisome, Efficacy, Nephrotoxicity, Renal, Toxicity. FINDINGS: ABLC is effective and well-tolerated in the treatment of systemic fungal infections and remains a valuable therapeutic option in a variety of immunocompromised patients due to its broad antifungal spectrum and rarity of resistance. LIMITATIONS: Data from randomised controlled trials of lipid-based amphotericin B formulations, as well as head-to-head comparison studies between ABLC and other antifungal agents are limited. In addition, the review uses a narrative approach and relies to a great extent on the authors' personal views and experiences.