Ibrutinib is an established treatment for relapsed/refractory (R/R) mantle cell lymphoma (MCL) and clinical trial data supports use at second line compared to later relapse. We aimed to investigate outcomes and tolerability for ibrutinib when given second line in a real-world setting. Our multicentre retrospective analysis included 211 R/R MCL patients, median age 73 years, receiving ibrutinib second-line within the United Kingdom's National Health Service. Overall response to ibrutinib was 69% (complete response 27%). The median progression-free survival (PFS) was 17Á8 months (95% CI 13Á1-22Á2) and median overall survival (OS) 23Á9 months (95% CI 15Á0-32Á8). Drug-related adverse event led to dose reduction in 10% of patients and discontinuation in 5%. In patients with progressive disease, accounting for 100 of 152 patients stopping ibrutinib, 43% received further systemic therapy. Post-ibrutinib rituximab, bendamustine and cytarabine (R-BAC) showed a trend toward improved survival compared to alternative systemic treatments (post-ibrutinib median OS 14Á0 months, 95% CI 8Á1-19Á8, vs. 3Á6 months, 95% CI 2Á6-4Á5, P = 0Á06). Our study confirms the clinical benefit and good tolerability of ibrutinib at first relapse in a real-world population. Patients progressing on ibrutinib had limited survival but outcomes with R-BAC in select patients were promising.

Scope The objective of this guideline is to provide healthcare professionals with clear guidance on the management of patients with Waldenström macroglobulinaemia. In individual patients, circumstances may dictate an alternative approach. Methodology This guideline was compiled according to the British Society for Haematology (BSH) process at http://www.b-s-h.org.uk/guidelines/proposing-and-writing-a-new-bsh-guideline/. Recommendations are based on a review of the literature using Medline, Pubmed, Embase, Central, Web of Science searches from beginning of 2013 (since the publication of the previous guidelines) up to November 2021. The following search terms were used: Waldenström(’s) macroglobulin(a)emia OR lymphoplasmacytic lymphoma, IgM(‐related) neuropathy OR cold h(a)emagglutinin disease OR cold agglutinin disease OR cryoglobulin(a)emia AND (for group a only) cytogenetic OR molecular OR mutation OR MYD88 OR CXCR4, management OR treatment OR transfusion OR supportive care OR plasma exchange OR plasmapheresis OR chemotherapy OR bendamustine OR bortezomib OR ibrutinib OR fludarabine OR dexamethasone OR cyclophosphamide OR rituximab OR everolimus, bone marrow transplantation OR stem cell transplantation. 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. Review of the manuscript was performed by the British Society for Haematology (BSH) Guidelines Committee Haemato‐Oncology Task Force, the BSH Guidelines Committee and the Haemato‐Oncology sounding board of BSH. It was also on the members section of the BSH website for comment. It has also been reviewed by UK Charity WMUK; these organisations do not necessarily approve or endorse the contents.

Background Chest keloids are a difficult sub‐group of scars to treat, likely secondary to the high wound tension in the area that promotes excessive fibroblast proliferation and collagen deposition. Excision and adjuvant radiotherapy has been demonstrated as an efficacious treatment for keloids in general, but no meta‐analysis exists to support the claims for chest keloids. This study aims to identify the rate of recurrence after surgical resection and radiotherapy on patients with chest keloids. Methods A search was performed using Embase, MEDLINE, Pubmed and Cochrane database on 22 December 2018 for terms ‘radiotherapy’, ‘keloid’ and ‘chest’. Papers included met a prospectively designed inclusion criteria assessed by multiple investigators. Results Twelve studies, including 1 randomized controlled trial, were included for a total of 400 patients with a chest keloid scar managed with surgical excision and adjuvant radiotherapy. Overall pooled‐estimate of recurrence rate was 22% (95% CI 12–32%). Meta‐regression did not demonstrate a significant effect for method of wound closure, type of radiotherapy, radiotherapy dose (BED10) and study type. Conclusion Excision and adjuvant radiotherapy represents an effective method of treatment for chest keloids, however sufficient prospective data, including randomized controlled trials, did not yet exist to support these findings. Further studies with sufficient sub‐group analysis for keloid location are required to add to the pool of literature that can be added to this meta‐analysis.

Background: Ibrutinib has transformed the clinical approach to relapsed mantle cell lymphoma (MCL) with those receiving ibrutinib at first relapse obtaining the greatest benefit encouraging use earlier in the treatment algorithm (Rule et al, 2019). However, the general applicability of clinical trial findings is not established and concerns regarding ibrutinib tolerability persist, especially in non-trial populations enriched for frailer patients with multiple co-morbidities. In the United Kingdom, ibrutinib is funded as standard of care at first relapse. This study has analysed the clinical effectiveness and tolerability of this approach in a non-clinical trial real world population. Method: 23 centres across the United Kingdom contributed data from consecutive patients treated with ibrutinib for MCL at first relapse. Patients received standard dose 560 mg OD, unless documented, and commenced treatment between August 2014 and April 2019. Response to therapy was defined as per Lugano classification (Cheson et al, 2014), although CR assessment by bone marrow biopsy was not always undertaken. Data was collected on baseline characteristics, including response to prior therapy, and MIPI at time of relapse. The study primary outcome was PFS. Predictors of progression were determined using univariate Cox regression. Results: 169 patients were included in the study. Median age at start of ibrutinib was 72 years (range 33 to 97) and 122 (72.2%) were male. At diagnosis 13.5% had blastoid histology; 59.3% Ki67 ≥30%; 32.0% received cytarabine based induction and 27.8% HSCT consolidation; 11.2% received low intensity frontline therapy (i.e. not fit for R-CHOP) due to frailty. Median PFS following frontline therapy was 21.4 months (95% CI 14.6 to 28.3) and 52.1% progressed within 2 years. At start of ibrutinib 52.2% were MIPI high risk; 23.9% were ECOG 2 or higher and 2.4% had CNS involvement. Overall response rate (ORR) to ibrutinib was 71.6% with 30.4% achieving CR/CRu. Estimated median PFS from start of ibrutinib was 16.5 months (95% CI 11.5 to 21.5) and estimated OS 23.9 months (95% CI 13.0 to 34.8), with median follow up 26 months. Median PFS for patients with early relapse to frontline therapy (progression of disease <2 years) was significantly shorter than those with more durable response (PFS 10.6 months vs. 20.6 months, HR 2.1, p=<0.001). Age ≥75 yrs and ECOG >1 were also negative predictors of PFS (see table 1 for univariate analysis). 10 patients (5.9%) received attenuated dose from start of therapy due to frailty and 20 patients (11.8%) underwent dose reductions while on therapy due to drug toxicity. Of 109 patients to discontinue ibrutinib 72 (66.1%) were due to progressive disease, 15 for consolidation alloHSCT (13.8%), 13 due to medical co-morbidities and unrelated death (11.9%), and 9 due to drug toxicity (8.3%), including 1 bleed. Only 5.3% of all patients stopped therapy due to drug toxicity. Patients ≥80 yrs were more likely to stop therapy early for reasons other than progressive disease or alloHSCT (OR 2.92, p=0.02), but frailer patients who received low intensity frontline therapy also showed a trend for more durable response with second-line ibrutinib (PFS 10.0 months versus 4.0 months, p=0.36) justifying use in this patient group. Conclusion: This study population is enriched for several recognised adverse prognostic markers, including older age and poor performance status, which is likely to explain differences in PFS relative to clinical trial data. Despite these features response rates were similar, and it is notable that 46.7% of evaluable pts achieved longer PFS with ibrutinib than preceding front-line therapy. It is reassuring that the proportion of patients stopping ibrutinib due to toxicity was similar to trial data and bleeding events that required alterations to therapy were rare (3 cases, 1.8%). Although ibrutinib represents a significant breakthrough with clear benefit to most patients the results also highlight that outcome for many remains poor. 40% of patients progressed within 1 year of starting ibrutinib and median OS post ibrutinib was only 3.6 months. 35.2% of patients died within 1 month of documented relapse suggesting many, predominantly older patients, were not fit for further therapy. Of the 53 pts surviving beyond 1 month median OS was 7.5 months and 21.9% lived beyond 1 year. Improved treatment strategies in the post-ibrutinib setting remains a priority. Disclosures Rule: Pharmacyclics: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Sunesis: Consultancy, Honoraria; TG Therapeutics: Consultancy, Honoraria; Napp: Consultancy; Roche: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Astra-Zeneca: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Kite: Consultancy. Eyre:Gilead: Consultancy, Honoraria, Other: commercial research support; Abbvie: Honoraria; Janssen: Honoraria; Roche: Honoraria. Furtado:Abbvie: Honoraria. Shah:ABBVIE: Consultancy. Campbell:Novartis: Consultancy, Other: Educational support; Takeda: Consultancy, Other: Educational support; Bristol Myers-Squibb: Other: Educational support; Roche: Other: Educational support; Celgene: Other: Educational support. McCarthy:Janssen: Honoraria, Other: Educational grant to attend meetings . Lambert:Takeda Pharmaceuticals: Other: Funding to attend a scientific conference in 2018. McKay:Epizyme: Consultancy, Honoraria. Osborne:Roche: Consultancy, Honoraria, Other: Travel, Speakers Bureau; Gilead: Consultancy; MSD: Consultancy; Takeda: Consultancy, Honoraria, Other: Travel, Speakers Bureau; Novartis: Other: Travel; Pfizer: Honoraria, Speakers Bureau; Servier: Consultancy. Bishton:Takeda: Other: Travel support, Research Funding; AbbVie: Research Funding; Celltrion: Membership on an entity's Board of Directors or advisory committees, Other: travel support; Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Roche: Other: Travel support, Research Funding. Crosbie:Janssen: Honoraria.

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