Now showing items 1-20 of 9450

    • Blood pressure (BP) status in Congenital Adrenal Hyperplasia (CAH) - longitudinal analysis of real world data from the I-CAH registry

      Lawrence, N. R.; Bacila, I.; Dawson, J.; Ali, S. R.; van den Akker, E. L. T.; Bachega, T.; Baronio, F.; Birkebaek, N. H.; Bonfig, W.; van der Grinten, C.; et al. (2022)
      Introduction: Data on BP in children with classic congenital adrenal hyperplasia (CAH) is inconsistent. Aim: To assess the trend in BP throughout childhood using data from the International CAH registry and compare this to nor mative data from the American Academy of Paediatrics (AAP). Method: This retrospective multi-centre study included 37 centres from 20 countries. BP data was analysed by Lambda Mu-Sigma (LMS) modelling to create smoothing reference curves. We subtracted the AAP median BP for age from the I-CAH regis try median BP for age, and conducted Bayesian multiple change point analysis to assess the age at which BP in the two populations converged. Results: A total of 546 patients (53% girls, 86% prescribed Fludrocortisone) with 6357 visits between 1988-2021 were avail able for analysis and 3181 visits had BP measurements available. Each centre contributed a median of 12 patients (Interquartile Range (IQR) 5, 23), with data from a median of 6.0 years (IQR 3.2, 12.7) follow up per patient. Median age at visit was 5.4 years (IQR 2.4, 10.6), maximum age at visit was 19.9 years, and median num ber of visits available per patient was 5 (IQR 2, 9). When compared against AAP normative BP values, the differ ence in median BP for age decreased with a clear plateau in both sexes. Systolic BP was higher in 1 year old CAH patients by 17.5 mmHg in boys and 13.6mmHg in girls, decreasing to a plateau of 6.2mmHg higher after age 7.7 years in boys and 5.3mmHg after age 13.3 years in girls. Diastolic BP was 22.9mmHg higher in boys and 18.3mmHg higher in girls at the age of 1 year, decreasing to a plateau of 3.2mmHg higher after age 6.7 years in boys and 3.3mmHg higher after age 6.3 years in girls. Conclusions: Analysis of real world data shows BP in children with classic CAH to be higher than normative values at an early age, but to plateau at age 8 years in males and 13 years in females to a level marginally higher than reference values. The difference was greater in diastolic BP at early ages, but greater in systolic BP after plateau. The impact of higher BP at these young ages on vas cular modelling and long term cardiovascular risk in CAH is unknown and warrants further investigation. Further analysis with covariates within this data set is ongoing, seeking to clarify other determinants of BP in CAH.
    • Neurocognitive outcomes after proton beam therapy for skull base tumours

      Gaito, Simona; Hwang, E.; Aznar, Marianne Camille; France, A.; Sitch, Peter; Crellin, A.; Holtsman, A. L.; Pan, Shermaine; Whitfield, Gillians A; Smith, Ed; et al. (2022)
      Evidence suggests that Proton Beam Therapy (PBT) may lessen the risk of neurocognitive decline (NCD) by reducing the dose to the normal brain as compared to conventional photon radiotherapy (XRT). We report the incidence of moderate-severe (Grade ≥3) NCD in adults treated for skull base chordomas and chondrosarcomas within the United Kingdom’s Proton Overseas Programme (POP). Material and Methods Baseline (pre-PBT) and follow-up clinical outcomes data were prospectively collected as part of a national PBT-outcomes registry, which started in 2008 . This registry is curated by a dedicated Proton Clinical Outcomes Unit. Specifically, late toxicities ≥G3 as per CTCAE (Common Terminology Criteria for Adverse Events) v4.0 definition, occurring later than 90 days after treatment completion, were recorded. This study focuses on the incidence of memory impairment (MI) in the adult (≥25 y) cohort. Results Between 2008-2018, 141 adult patients were treated for skull base chordomas (77 patients, 54.6%) and chondrosarcomas (64 patients, 45.4%) via the POP (the majority -62.8%- treated at the University of Florida PBT Institute). Median age at treatment was 51 years (range 26-77). Median prescription dose was 73.8 GyRBE (70-75.6), with a median dose per fraction of 1.8 Gy (1.2-2.1). Of note, the median dose for chondrosarcomas was 70.2 GyRBE (70-75.6), whereas the median dose for chordomas was 73.8 GyRBE (72-75.6). Median follow up was 39 months (0-138). On clinical assessment, 4 patients (2 chordomas, 2 chondrosarcomas) were reported with G3 MI after a median time of 43 months (27-49). None of them had impaired memory at baseline, nor relevant neurological comorbidities. Median age of those who developed G3 MI was 63 y (39-70). Median prescription dose was 72.9 GyRBE (70-73.8). Plans were available for 3 of these 4 patients. Relevant dose statistics to hippocampi and temporal lobes were extracted. Dmean to the omo- and contralateral hippocampi in these 3 patient plans were: patient 1) 33.7 and 11.6 GyRBE; patient 2) 28.1 and 24.4 Gy; patient 3) 8.7 and 8.2 GyRBE, respectively. V20 to the omo- and contralateral temporal lobes in the same patients were: patient 1) 47% and 10%; patient 2) 29% and 28.7%; patient 3) 30% and 28%, respectively. Suggested constraints for these structures are: Dmean < 20 Gy to the hippocampi and V20Gy <10% to the temporal lobes. Conclusion Our results indicate that adult patients undergoing high dose radiation for radioresistant tumours may experience detrimental effects on memory. Neurocognitive baseline and follow-up assessment is not routinely performed in this age group but might be appropriate to explore which domains of cognitive function are mainly affected. Larger cohorts are warranted to establish predictive factors and better understand dose volume effect of brain structures and neurocognitive sequelae.
    • Long-term follow up and translational data from the reoglio phase ib trial of Gm-Csf and intravenous pelareorep (reovirus) alongside standard of care in gbm

      Short, S.; Kendall, J.; West, E.; Chalmers, A.; McBain, Catherine A; Melcher, A.; Collinson, F.; Phillip, R.; Brown, S.; Samson, A.; et al. (2022)
      BACKGROUND We previously reported safety data from a phase Ib, open-label study of intravenous oncolytic virus pelareorep with GM-CSF alongside standard chemoradiotherapy in newly diagnosed glioblastoma confirming that the combination is well tolerated. We now report on long-term follow up and analysis of translational samples from tumour and blood in a subset of patients. METHODS 15 patients with newly diagnosed GBM were treated with GM-CSF 50μg subcutaneously on days 1-3 and intravenous pelareorep on days 4-5 in weeks 1 and 4 of chemoradiotherapy, and subsequently in week 1 of each adjuvant temozolomide course: 7 patients received 1x1010TCID50 (dose level 1); 8 received 3x1010TCID50 (dose level 2). The primary objective was to determine the maximum tolerated dose of pelareorep and GM-CSF with standard chemoradiotherapy. Following a protocol amendment we also collected survival data in all patients up to August 2021. Serial blood samples were taken from three patients, at baseline, during chemoradiotherapy and in the first adjuvant cycle. Peripheral blood mononuclear cells were analysed for immune checkpoint expression by flow cytometry, RNAseq gene expression and T-cell receptor clonality, whilst plasma cytokines were quantified by Luminex. RESULTS This combination was well tolerated with 87% of patients completing treatment as planned. Survival data analysis showed that median OS was 12.6 months in dose level 1 and 16.1 months in dose level 2, median OS for all patients was 13.1 months. The 24-month survival estimate for all patients was 25.0%, 16.7% for dose level 1 and 33.3% for dose level 2. One patient in dose level 1 remains alive at 43 months post registration without further treatment. Laboratory data showed that pelareorep infusion resulted in inflammatory cytokine and chemokine secretion, immune checkpoint modulation, and upregulation of inflammatory pathways. There was also increased peripheral clonal tumour-specific T-cell proliferation following pelareorep infusion. CONCLUSION Although based on small numbers, these long-term follow up data suggest this may be an active combination in a subset of GBM patients. Translational data confirm that pelareorep potentially activates tumour-targeting immune pathways in GBM, with consequential immune checkpoint modulation. These data support a combination clinical trial of pelareorep, radiotherapy and immune checkpoint blockade in GBM.
    • Real-world outcomes with ipilimumab and nivolumab in advanced melanoma: a multicentre retrospective study

      Serra-Bellver, Patricio; Versluis, J. M.; Oberoi, Honey K; Zhou, Cong; Slattery, T. D.; Khan, Y.; Patrinely, J. R.; Pires da Silva, I.; Martínez-Vila, C.; Cook, Natalie; et al. (2022)
      Purpose: To assess efficacy and toxicity of combination immunotherapy with ipilimumab plus nivolumab in routine practice in a retrospective multicentre cohort of patients with advanced melanoma. Patients and methods: This retrospective analysis included patients with advanced melanoma treated with ipilimumab and nivolumab between October 2015 and January 2020 at six centres in Australia, Europe and the United States of America. We describe efficacy outcomes (overall survival [OS], progression-free survival [PFS] and objective response rate [ORR]) in treatment-naïve and pre-treated patients, with and without brain metastases, plus treatment-related adverse events (trAEs) in all patients treated. Results: A total of 697 patients were identified; 472 were treatment-naïve of which 138 (29.2%) had brain metastases, and 225 were previously treated of which 102 (45.3%) had brain metastases. At baseline, 32.3% had stage M1c and 34.4% stage M1d disease. Lactate dehydrogenase was high in 280 patients (40.2%). With a median follow-up of 25.9 months, median OS in the 334 treatment-naïve patients without brain metastases was 53.7 months (95% confidence interval [CI] 40.8-NR) and 38.7 months (95% CI 18.6-NR) for the 138 treatment-naïve patients with brain metastases. For the entire cohort the ORR was 48%, for treatment-naïve patients without brain metastases ORR was 56.6% with a median PFS of was 13.7 months (95% CI 9.6-26.5). Median PFS was 7.9 months (95% CI 5.8-10.4) and OS 38 months (95% CI 31-NR) for the entire cohort. Grade 3-4 trAE were reported in 44% of patients, and 4 (0.7%) treatment-related deaths (1 pneumonitis, 2 myocarditis and 1 colitis) were recorded. Conclusion: The outcome and toxicity of combination immunotherapy with ipilimumab and nivolumab in a real-world patient population are similar to those reported in pivotal trials.
    • Severity of dementia and survival in patients diagnosed with colorectal cancer: a national cohort study in England and Wales

      Kuryba, A. J.; Boyle, J. M.; van der Meulen, J.; Aggarwal, A.; Walker, K.; Fearnhead, N. S.; Braun, Michael S; Clinical Effectiveness Unit, Royal College of Surgeons of England, London, UK; Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine, London, UK (2022)
      Aims: There is little evidence about the survival of patients with colorectal cancer (CRC) also diagnosed with dementia. We quantified dementia severity and estimated how it is associated with 2-year overall survival. Materials and methods: Records of patients aged 65 years or older diagnosed with CRC in England and Wales were identified. A novel proxy for dementia severity combined dementia diagnosis in administrative hospital data with Eastern Cooperative Oncology Group performance status. Cox regression was used to estimate hazard ratios with and without risk adjustment. Results: In total, 4033 of 105 250 CRC patients (3.8%) had dementia recorded. Two-year survival decreased with increasing dementia severity from 65.4% without dementia, 53.5% with mild dementia, 33.0% with moderate dementia to 16.5% with severe dementia (hazard ratio comparing severe with no dementia: 2.97; 95% confidence interval 2.79, 3.16). Risk adjustment for comorbidity and cancer stage reduced this association slightly (hazard ratio 2.52; 95% confidence interval 2.37, 2.68) and additional adjustment for treatment factors reduced it further (hazard ratio 1.60; 95% confidence interval 1.50, 1.70). Conclusions: Survival of CRC patients varied strongly according to dementia severity, suggesting that a 'one-size-fits-all' policy for the care of CRC patients with dementia is not appropriate. Comprehensive assessment of cancer patients with dementia that considers dementia severity is essential in a shared decision-making process that ensures patients receive the most appropriate treatment for their individual needs and preferences.
    • Early mortality risk with non-intensive acute myeloid leukemia (AML) therapies: analysis of 1336 patients from MRC/NCRI and SWOG

      Othus, M.; Thomas, I.; Wang, X.; Ariti, C.; Mehta, P.; Sydenham, M.; Hills, R. K.; Burnett, A. K.; Nand, S.; Assouline, S.; et al. (2022)
      None
    • The correlation between pre-treatment symptoms, acute and late toxicity and patient-reported health-related quality of life in non-small cell lung cancer patients: Results of the REQUITE study

      van der Weijst, L.; Azria, D.; Berkovic, P.; Boisselier, P.; Briers, E.; Bultijnck, R.; Chang-Claude, J.; Choudhury, Ananya; Defraene, G.; Demontois, S.; et al. (2022)
      Background and purpose: To investigate the association between clinician-scored toxicities and patient-reported health-related quality of life (HRQoL), in early-stage (ES-) and locally-advanced (LA-) non-small cell lung cancer (NSCLC) patients receiving loco-regional radiotherapy, included in the international real-world REQUITE study. Materials and methods: Clinicians scored eleven radiotherapy-related toxicities (and baseline symptoms) with the Common Terminology Criteria for Adverse Events version 4. HRQoL was assessed with the European Organization for Research and Treatment of Cancer core HRQoL questionnaire (EORTC-QLQ-C30). Statistical analyses used the mixed-model method; statistical significance was set at p = 0.01. Analyses were performed for baseline and subsequent time points up to 2 years after radiotherapy and per treatment modality, radiotherapy technique and disease stage. Results: Data of 435 patients were analysed. Pre-treatment, overall symptoms, dyspnea, chest wall pain, dysphagia and cough impacted overall HRQoL and specific domains. At subsequent time points, cough and dysphagia were overtaken by pericarditis in affecting HRQoL. Toxicities during concurrent chemo-radiotherapy and 3-dimensional radiotherapy had the most impact on HRQoL. Conversely, toxicities in sequential chemo-radiotherapy and SBRT had limited impact on patients' HRQoL. Stage impacts the correlations: LA-NSCLC patients are more adversely affected by toxicity than ES-NSCLC patients, mimicking the results of radiotherapy technique and treatment modality. Conclusion: Pre-treatment symptoms and acute/late toxicities variously impact HRQoL of ES- and LA-NSCLC patients undergoing different treatment approaches and radiotherapy techniques. Throughout the disease, dyspnea seems crucial in this association, highlighting the additional effect of co-existing comorbidities. Our data call for optimized radiotherapy limiting toxicities that may affect patients' HRQoL.
    • Treatment-induced mucositis in oncology

      Jasiewicz, Francis; Qurban, Zeeshan; Hughes, Christopher; Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK. (2022)
      Almost all cancer therapies lead to a wide array of side effects, owing to the disruption of normal physiological processes and alteration of immunological responses. Of these, mucositis is one of the most commonly encountered side effects, presenting in about 20-40% of all patients receiving chemotherapy and 80% of those being treated with radiotherapy for head and neck malignancies. This article provides a brief introduction and comprehensive overview of the various treatment modalities used in managing this complication. The key to management is a multidisciplinary approach, revolving around pain control, oral hygiene, nutritional support and management of superimposed infection. The scarcity of therapeutic options for prevention or treatment of mucositis has resulted in clinical difficulty in controlling it, which, in turn, seriously affects the patient's quality of life and cancer management, contributing to patient morbidity and mortality.
    • Fast and Low-GPU-memory abdomen CT organ segmentation: The FLARE challenge

      Ma, J.; Zhang, Y.; Gu, S.; An, X.; Wang, Z.; Ge, C.; Wang, C.; Zhang, F.; Wang, Y.; Xu, Y.; et al. (2022)
      Automatic segmentation of abdominal organs in CT scans plays an important role in clinical practice. However, most existing benchmarks and datasets only focus on segmentation accuracy, while the model efficiency and its accuracy on the testing cases from different medical centers have not been evaluated. To comprehensively benchmark abdominal organ segmentation methods, we organized the first Fast and Low GPU memory Abdominal oRgan sEgmentation (FLARE) challenge, where the segmentation methods were encouraged to achieve high accuracy on the testing cases from different medical centers, fast inference speed, and low GPU memory consumption, simultaneously. The winning method surpassed the existing state-of-the-art method, achieving a 19× faster inference speed and reducing the GPU memory consumption by 60% with comparable accuracy. We provide a summary of the top methods, make their code and Docker containers publicly available, and give practical suggestions on building accurate and efficient abdominal organ segmentation models. The FLARE challenge remains open for future submissions through a live platform for benchmarking further methodology developments at https://flare.grand-challenge.org/.
    • IBCL-460 Subcutaneouse pcoritamab with rituximab + lenalidomide (R(2)) in patients with relapsed or refractory (R/R) follicular lymphoma (FL): update from phase 1/2 trial

      Falchi, L.; Leppä, S.; Wahlin, B. E.; Nijland, M.; Christensen, J. H.; de Vos, S.; Holte, H.; Linton, Kim M; Abbas, A.; Wang, L.; et al. (2022)
      Context: R/R FL is associated with a poor prognosis and remains incurable; thus, better treatment options are needed. Epcoritamab is a subcutaneously administered CD3xCD20 bispecifi c antibody that has shown substantial antitumor activity in R/R FL. Objective: Evaluate safety and effi cacy of epcoritamab with R2 in patients with R/R FL in arm 2 of a phase 1/2 open-label trial (EPCORE NHL-2; NCT04663347). Patients: Adults with R/R CD20+ FL were included. As of December 1, 2021, 30 patients (median age, 68 y) had enrolled. Interventions: Patients received subcutaneous epcoritamab (QW, cycle [C] 1–3; Q2W, C4–9; Q4W, C10 up to 2 y) + R2 for 12 cycles of 28 d. Step-up dosing and corticosteroid prophylaxis were required. Results: Of the 30 patients (epcoritamab 24 mg, n=3; 48 mg, n=27), 21 (70%) had stage IV disease and 20 (67%) had FLIPI scores 3–5. Median (range) number of prior lines of therapy was 1 (1–5), 30% had primary refractory disease, and 40% had disease progression within 24 mo after starting fi rst-line treatment. At a median (range) follow-up of 5.1 mo (0.8–12.3), 25 patients (83%) remained on treatment; 5 patients discontinued treatment due to progression (n=2), AEs (n=2), or consent withdrawal (n=1). Common treatment-emergent AEs (TEAEs) of any grade (G) included infections (57%), injection-site reactions (50%), constipation (37%), fatigue (37%), and neutropenia (37%). CRS events occurred in 15 patients (50%; G1–2 43%, G3 7%), primarily in C1. All CRS events resolved; 3 patients were treated with tocilizumab, and 1 patient discontinued treatment due to CRS. One patient experienced G2 ICANS. No fatal TEAEs occurred. Overall response rate for the 27 evaluable patients was 100%; 93% had a complete metabolic response (CMR) and 7% had a partial metabolic response by PET-CT. As of the data cut, the longest duration of response was 7.0+ mo and ongoing. Conclusions: Subcutaneous epcoritamab + R2 exhibits promising effi cacy, including a high CMR rate, in patients with R/R FL. The safety profi le was consistent with prior data. Updated data will be presented.
    • Access to and affordability of CAR T-cell therapy in multiple myeloma: an EBMT position paper

      Gagelmann, N.; Sureda, A.; Montoto, S.; Murray, John; Bolaños, N.; Kenyon, M.; Beksac, M.; Schönland, S.; Hayden, P.; Scheurer, H.; et al. (2022)
      Chimeric antigen receptor (CAR) T-cell therapy is a promising immunotherapeutic approach in the treatment of multiple myeloma, and the recent approval of the first two CAR T-cell products could result in improved outcomes. However, it remains a complex and expensive technology, which poses challenges to health-care systems and society in general, especially in times of crises. This potentially accelerates pre-existing inequalities as access to CAR T-cell therapy varies, both between countries, depending on the level of economic development, and within countries, due to structural disparities in access to quality health care-a parameter strongly correlated with socioeconomic status, ethnicity, and lifestyle. Here, we identify two important issues: affordability and access to CAR T-cell treatment. This consensus statement from clinical investigators, clinicians, nurses, and patients from the European Society for Blood and Marrow Transplantation (EBMT) proposes solutions as part of an innovative collaborative strategy to make CAR T-cell therapy accessible to all patients with multiple myeloma.
    • Current best practice for bladder cancer: a narrative review of diagnostics and treatments

      Compérat, E.; Amin, M. B.; Cathomas, R.; Choudhury, Ananya; De Santis, M.; Kamat, A.; Stenzl, A.; Thoeny, H. C.; Witjes, J. A.; Department of Pathology, Tenon Hospital, Sorbonne University, Paris, France; Department of Pathology, Medical University of Vienna, Vienna, Austria (2022)
      This Seminar presents the current best practice for the diagnosis and management of bladder cancer. The scope of this Seminar ranges from current challenges in pathology, such as the evolving histological and molecular classification of disease, to advances in personalised medicine and novel imaging approaches. We discuss the current role of radiotherapy, surgical management of non-muscle-invasive and muscle-invasive disease, highlight the challenges of treatment of metastatic bladder cancer, and discuss the latest developments in systemic therapy. This Seminar is intended to provide physicians with knowledge of current issues in bladder cancer.
    • ABCL-452 First-line treatment with subcutaneous epcoritamab + R-CHOP in patients with high-risk diffuse large B-cell lymphoma (DLBCL): phase 1/2 data update

      Falchi, L.; Offner, F.; Belada, D.; Brody, J.; Linton, Kim M; Karimi, Y.; Cordoba, R.; Snauwaert, S.; Abbas, A.; Wang, L.; et al. (2022)
      Context: Patients with newly diagnosed high-risk DLBCL have suboptimal outcomes. Subcutaneous epcoritamab is a CD3xCD20 bispecifi c antibody well suited for combination with standard of care therapies. Objective: Evaluate safety and effi cacy of epcoritamab + rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in previously untreated patients with high-risk DLBCL in arm 1 of a phase 1/2, open label trial (EPCORE NHL-2; NCT04663347). Patients: Adults with previously untreated CD20+ DLBCL and IPI 3 were included. As of December 1, 2021, 33 patients (median age, 66 y) had enrolled. Interventions: Patients received subcutaneous epcoritamab (QW, cycles 1–4; Q3W, cycles 5–6) + R-CHOP for 6 cycles (21 d) followed by epcoritamab monotherapy Q4W up to 1 y (in cycles of 28 d). Step-up dosing and corticosteroid prophylaxis were required. Results: All 33 patients treated (epcoritamab 24 mg, n=4; 48 mg, n=29) had IPI 3, and 24% had double/triple hit DLBCL. Median follow-up was 3 mo (range, 0–9.7), median number of total cycles initiated was 5 (1–13), and 94% of patients (31/33) remained on treatment. Treatment-emergent AEs (TEAEs) in 35% of patients were neutropenia (48%; febrile neutropenia in 9% of all patients), CRS (45%), infections (42%), anemia (39%), and injection-site reactions (36%). No TEAEs led to epcoritamab discontinuation. Most CRS events were low grade (42% grade [G] 1–2, 3% G3), occurred in cycle 1, and resolved after a median of 2 d (1–11); 4 patients received tocilizumab. G2 ICANS occurred in 1 patient. No fatal TEAEs occurred. In effi cacy-evaluable patients, the overall response rate (ORR) was 96% (24/25); 68% (17/25) had complete metabolic response (CMR) by PET-CT. In the 10 patients who completed 6 cycles of R-CHOP by the cutoff date, ORR and CMR rate were 100% and 90%, respectively; all patients remained in response at data cutoff (longest duration of response, 7.1+ mo, ongoing). Conclusions: Epcoritamab + R-CHOP had manageable safety, mostly low-grade CRS that did not lead to treatment discontinuation, and high response rates in patients with previously untreated DLBCL. Updated data will be presented.
    • ABCL-316 Health-related quality of life and tolerability in patients with/without skin toxicity during loncastuximab tesirine treatment in a phase 2 clinical trial (LOTIS-2)

      Spira, A.; Zhou, X.; Liao, L.; Yu, E.; Chen, L.; Lau, A.; Wang, Y.; Gnanasakthy, A.; Radford, John A; Hamadani, M.; et al. (2022)
      Context: Skin toxicity was commonly reported among patients treated with loncastuximab tesirine (loncastuximab tesirine-lpyl; Lonca). Most skin toxicities (~90%) were grade 1 or 2, but their impact on health-related quality of life (HRQOL) was unknown. Objective: This post hoc analysis assesses whether skin toxicity is associated with HRQOL and patient tolerability to Lonca. Design: The LOTIS-2 study (NCT03589469) is a single-arm, open label, phase 2 study of 145 adult patients with relapsed/refractory diffuse large B-cell lymphoma after 2 prior treatments. Patients received Lonca as an intravenous infusion on day 1 of each 3-week treatment cycle for up to 1 year. EQ-5D and FACT-Lym scores were collected. Mean changes from baseline were summarized by visit and with/without skin toxicity. The least-squares means of the differences were estimated using the analysis of covariance models to adjust for age, sex, race, baseline score, and tumor response status. Treatment tolerability was measured using FACT-Lym item GP5 (“I am bothered by side effects of treatment”). Results: Patients with an HRQOL baseline score and a postbaseline score (n=130) were included in the analysis (median age, 66 years; 59% male; and 88% White). With a median of 4 cycles of treatment (range, 1–26), 41% of patients experienced skin toxicity during treatment, >80% due to non-photosensitivity cutaneous reactions. Among all 9 evaluated scores (EQ-5D visual analog scale, FACT-Lym subscale, and composite scores) for visits up to cycle 9 (n20), there were no signifi cant differences (P>0.05) between patients with and without skin toxicity except for the FACT-Lym total at cycle 9 (worse in patients with skin toxicity). A majority of patients (60%) were “not at all” or “a little bit” bothered in both groups at each cycle, although a higher percentage of patients with skin toxicity reported “a little bit” than those without skin toxicity after 2 cycles. Conclusions: Patients with skin toxicity while receiving Lonca did not experience different HRQOL compared with patients without skin toxicity in most visits. Lonca was tolerated well even among patients with skin toxicity. (Sponsored by ADC Therapeutics)..
    • HL-339 Camidanlumab tesirine: updated efficacy and safety in an open-label, multicenter, phase 2 study of patients with relapsed or refractory classical Hodgkin Lymphoma (R/R cHL)

      Carlo-Stella, C.; Ansell, S.; Zinzani, P. L.; Radford, John A; Maddocks, K.; Pinto, A.; Collins, G. P.; Bachanova, V.; Bartlett, N.; Bence-Bruckler, I.; et al. (2022)
      Context: Camidanlumab tesirine (Cami), an antibody–drug conjugate comprising a human IgG1 anti-CD25 monoclonal antibody conjugated to a pyrrolobenzodiazepine (PBD) dimer, displayed antitumor activity and manageable toxicity in a phase 1 trial in lymphoma, including R/R cHL (NCT02432235). Objective: Present updated effi cacy and safety data from a phase 2 study of Cami monotherapy in R/R cHL (NCT04052997). Methods: Patients with R/R cHL and 3 prior systemic therapies including brentuximab vedotin and anti–PD-1 were enrolled. Primary endpoint: overall response rate (ORR). Patients received Cami 45 µg/kg on Day 1 of each 3-week cycle (2 cycles), then 30 µg/kg (subsequent cycles) for up to 1 year. Results: Enrollment is complete (N=117). Median age was 37 years, 62% of patients were male, and 95% had an ECOG score of 0–1. Fourteen patients (12.0%) withdrew to undergo transplant (12 [10.3%] received transplant and were censored). In the all-treated population (N=117), ORR was 70.1% (82/117; 95% CI: 60.9–78.2); 33.3% (39/117) had complete response (CR). At median (range) follow-up of 10.7 (1.2– 25.2+) months, the median (95% CI) duration of response (DOR) was 13.7 months (7.4–14.7) for all responders, 14.5 (7.4–not reached, NR) months and 7.9 (3.8–NR) months for patients with CR or PR. Median (95% CI) progression-free survival (PFS) was 9.1 (5.1–15.0) months. All-grade treatment-emergent AEs (TEAEs) in 25% of 117 patients were fatigue (38.5%), maculopapular rash (MR, 32.5%), pyrexia (29.9%), nausea (27.4%), and rash (26.5%). Grade 3 TEAEs in 5% of patients were thrombocytopenia (9.4%), anemia (8.5%), hypophosphatemia (7.7%), neutropenia (7.7%), MR (6.8%), and lymphopenia (5.1%). TEAEs considered immune-related (IR) occurred in 32.5% of patients; Grade 3 IR AEs (TEAEs and non-TEAEs; 8.5%). Guillain–Barré syndrome (GBS)/polyradiculopathy occurred in 8 patients (6.8%). At data cutoff, 4 cases had recovered (grade 2, n=2; grade 4, n=2); 4 had not recovered (grade 4, n=1; grade 3, n=3). Conclusions: Cami demonstrated an ORR of 70.1% (CR: 33.3%) with an encouraging median DOR of 13.7 months and median PFS of 9.1 months. Safety is consistent with prior fi ndings, including similar incidence rates of GBS/polyradiculopathy.
    • HL-507 First-Line brentuximab vedotin plus chemotherapy improves overall survival in patients with stage III/IV classical Hodgkin Lymphoma: an updated analysis of ECHELON-1

      Straus, D.; Radford, John A; Connors, J.; Kim, W. S.; Gallamini, A.; Ramchandren, R.; Friedberg, J.; Advani, R.; Hutchings, M.; Evens, A.; et al. (2022)
      Context: Overall survival (OS) benefi t from upfront treatment with new over existing approaches has never been shown in fi rst line (1L) classical Hodgkin lymphoma (cHL). With newer therapies for relapsed/refractory disease, demonstrating improved OS with 1L therapy has been challenging. In ECHELON-1 (NCT01712490), 5-year follow- up analyses supported a long-term progression-free survival (PFS) benefi t with 1L brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (A+AVD) vs doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) in patients with stage Ill/ IV cHL. A+AVD had a manageable long-term safety profi le, with fewer second malignancies and more pregnancies reported vs ABVD (Connors et al, NEJM 2018; Straus et al, Lancet Haematol 2021). We report a prespecifi ed OS analysis after approximately 6 years’ follow-up. Interventions: Patients were randomized 1:1 to receive up to 6 cycles of A+AVD (n=664) or ABVD (n=670) on day 1 and 15, every 28 days. Main Outcomes Measures: OS was the key prespecifi ed secondary endpoint. Results: At a median follow-up of 73 months, 39 and 64 deaths occurred in A+AVD and ABVD arms, respectively; OS signifi cantly favored A+AVD (hazard ratio [HR] 0.590; 95% confi dence interval [Cl] 0.396–0.879; p = 0.009). Estimated 6-year OS rates (95% Cl) were 93.9% (91.6– 95.5) vs 89.4% (86.6–91.7) with A+AVD vs ABVD, respectively, with a consistently higher OS across prespecifi ed subgroups. The 6-year PFS estimate was 82.3% (79.1–85.0) vs 74.5% (70.8–77.7) with A+AVD vs ABVD, respectively (HR 0.678 [95% Cl 0.532– 0.863]). Overall, A+AVD and ABVD had comparable long-term safety profi les. By the last follow-up, 86% (379/443) of treatment related peripheral neuropathy cases in the A+AVD arm and 87% (249/286) in the ABVD arm either completely resolved (72% vs 79%, respectively) or were improving (14% vs 8%, respectively). Fewer second malignancies (23 vs 32) and more pregnancies (49 vs 28) were reported in the A+AVD vs ABVD arm, respectively. No new safety signals were identifi ed. Conclusions: In this updated analysis, A+AVD treatment resulted in a 41% reduction in risk of death vs ABVD, with a manageable safety profi le. These outcomes are important in advancing treatment of patients with previously untreated stage Ill/IV cHL.
    • ABCL-272 A phase 2, open-label study of loncastuximab tesirine in combination with rituximab (Lonca-R) in previously untreated unfit/frail patients with diffuse large B-cell lymphoma (LOTIS-9)

      Westin, J.; Burke, J. M.; Chapman, A. E.; Kilavuz, T.; Xu, C.; Shmuely, Y.; Radford, John A; University of Texas MD Anderson Cancer Center, Houston, USA (2022)
      Background: Rituximab in combination with chemotherapy (R [rituximab]-CHOP [cyclophosphamide, doxorubicin, vincristine, and prednisone]) is standard fi rst-line therapy for patients with diffuse large B-cell lymphoma (DLBCL). With an aging population, unfi t or frail patients who may not tolerate R-CHOP represent an increasing unmet need. Aim: To determine the safety and effi cacy of the approved loncastuximab tesirine (loncastuximab tesirine-lpyp; Lonca), an antibody-drug conjugate comprising a humanized anti CD19 monoclonal antibody conjugated to a pyrrolobenzodiazepine dimer toxin, in combination with rituximab (Lonca-R) in previously untreated unfi t/frail patients (LOTIS-9; NCT05144009). Methods: This is a phase 2, open-label, response-adapted study of Lonca-R in previously untreated unfi t (Cohort A) or frail (Cohort B) patients with DLBCL. The simplifi ed geriatric assessment (sGA), which identifi es three categories of fi tness (fi t, unfi t, and frail) based on age, activities of daily living (ADL), and instrumental activities of daily living (IADL), and the Cumulative Illness Rating Scale for Geriatrics (CIRS-G) will be utilized to differentiate the cohorts. Key inclusion criteria include diagnosis of DLBCL (including DLBCL transformed from indolent lymphoma), high-grade B-cell lymphoma, or grade 3b follicular lymphoma; Eastern Cooperative Oncology Group performance status of 0–2; and measurable disease (2014 Lugano Classifi cation). Each cohort will enroll 40 patients, with fi tness (Cohort A) and frailty (Cohort B) assessed using the sGA. Primary objectives: effi cacy (Cohorts A and B) and tolerability (Cohort B) of Lonca-R. Primary endpoints: complete response (CR) rate (both Cohorts) and tolerability (Cohort B) following completion of 4 therapy cycles. Lonca-R treatment consists of R intravenously [IV] 375 mg/m2 on day 1/cycles 1–4, (subcutaneously allowed starting at C2), Lonca 150 µg/kg IV on day 2/cycle 1 and day 1/cycle 2, and 75 µg/kg IV on day 1/cycles 3 and 4. Patients who achieve CR or partial response (PR) after three cycles will receive 1 or 3 additional cycles of Lonca-R, respectively. Cohort B patients who achieve stable disease may continue to receive 3 additional cycles. All patients will be followed for up to 5 years. Results: The study opened for recruitment in April 2022. This abstract was accepted for publication only at the 2022 EHA Congress. Funding: ADC Therapeutics SA; medical writing: CiTRUS Health Group.
    • Evaluation of the individual activity descriptors of the mMRC breathlessness scale: a mixed method study

      Yorke, Janelle; Khan, N.; Garrow, A.; Tyson, S.; Singh, D.; Vestbo, J.; Jones, P. W.; Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK (2022)
      Purpose: The modified-Medical Research Council (mMRC) breathlessness scale consists of five grades that contain of a description of different activities. It has wide utility in the assessment of disability due to breathlessness but was originally developed before the advent of modern psychometric methodology and, for example contains more than one activity per grade. We conducted an evaluation of the mMRC structure. Patients and methods: Cognitive debriefing was conducted with COPD patients to elicit their understanding of each mMRC activity. In a cross-sectional study, patients completed the mMRC scale (grades 0-4) and an MRC-Expanded (MRC-Ex) version consisting of 10-items, each containing one mMRC activity. Each activity was then given a 4-point response scale (0 "not at all" to 4 "all of the time") and all 10 items were given to 203 patients to complete Rasch analysis and assess the pattern of MRC item severity and its hierarchical structure. Results: Cognitive debriefing with 36 patients suggested ambiguity with the term "strenuous exercise" and perceived severity differences between mMRC activities. 203 patients completed the mMRC-Ex. Strenuous exercise was located third on the ascending severity scale. Rasch identified the mildest term was "walking up a slight hill" (logit -2.76) and "too breathless to leave the house" was the most severe (logit 3.42). Conclusion: This analysis showed that items that were combined into a single mMRC grade may be widely separated in terms of perceived severity when assessed individually. This suggests that mMRC grades as a measure of individual disability related to breathlessness contain significant ambiguity due to the combination of activities of different degrees of perceived severity into a single grade.
    • Online symptom monitoring during pelvic radiotherapy: randomised pilot trial of eRAPID intervention

      Holch, P.; Absolom, K. L.; Henry, A. M.; Walker, K.; Gibson, A.; Hudson, E.; Rogers, Z.; Holmes, M.; Peacock, R.; Pini, S.; et al. (2022)
      Background: Radiotherapy and chemo-radiotherapy for pelvic cancers increase survival but are associated with serious treatment-related symptoms. Electronic-patient self-Reporting of Adverse-events: Patient Information and aDvice (eRAPID) is a secure online system for patients to self-report symptoms, generating immediate advice for hospital contact or self-management. This pilot study aimed to establish feasibility and acceptability of the system. Methods: In a prospective two-centre randomised parallel-group pilot study. Patients undergoing radical pelvic radiotherapy for prostate cancer (prostateRT) or chemo-radiotherapy for lower gastrointestinal and gynaecological cancers (chemoRT) were randomised to usual care (UC) or eRAPID (weekly online symptom reporting for 12, 18 & 24 weeks). Primary outcomes were recruitment/attrition, study completion and patient adherence. Secondary outcomes were impact on hospital services and performance of patient outcome measures. Missing data, floor/ceiling effects, and mean change scores were examined for FACT-G, EORTC-QLQ-C30, self-efficacy, EQ5D-5L. Results: From 228 patients approached, 167 (73.2%) were consented and randomised (83-eRAPID,84-UC;87-prostateRT;80-chemoRT). 150/167 completed 24 study weeks. Only 16 patients (9.6%) withdrew (10-eRAPID; 6-UC). In the eRAPID arm, completion rates were higher in patients treated with prostateRT compared to chemoRT: week 1 93% vs 69%; week 2 93% vs 68%; week 12 69% vs 55%). Overall over 50% of online reports triggered self-management advice for milder AEs. Unscheduled hospital contact was low, with no difference between eRAPID and UC. Return rates for outcome measures were excellent in prostateRT (97%-91%; 6-24 weeks) but lower in chemoRT (95%-55%; 6-24 weeks). Missing data was low (1%-4.1%), ceiling effects were evident in EQ5D-5L, self-efficacy-scale and FACT-PWB. At 6-weeks the chemoRT-eRAPID group showed less deterioration in FACT-G, EORTC QLQ-C30 and EQ5D-VAS than UC, after baseline adjustment. Conclusions: eRAPID was successfully added to UC at two cancer centres in different patient populations. Acceptability and feasibility was confirmed with excellent adherence by prostate patients, but lower by those undergoing chemoRT for gynaecological cancers.
    • Impact of Covid-19 on lung cancer and mesothelioma specialist nurses: A survey of experiences and perceptions

      Hargreaves, S.; Clayton, K.; Creech, L.; Darlison, L.; Ejegi-Memeh, S.; Fenemore, Jackie; Gardiner, C.; Taylor, B.; Tod, A.; Mesothelioma UK Research Centre, University of Sheffield, UK. (2022)
      Purpose: The covid-19 global pandemic has impacted on nurses who have rapidly adapted to new ways of working, and experienced negative impacts due to over-stretched services. Two surveys captured the experiences of lung cancer and mesothelioma specialist nurses in the United Kingdom (UK) in 2020, but the impact of later stages of the pandemic was unknown. This study aimed to explore the impact of covid-19 on lung Cancer and mesothelioma nurses since January 2021, the second wave of the pandemic. Methods: An online cross-sectional survey with both open and closed questions explored the impact of covid-19 on ways of working and workload, quality of care, and health and wellbeing. The survey was open to UK based lung cancer and mesothelioma advanced or specialist nurses. Results: 85 nurses responded to the survey. The majority were Clinical Nurse Specialists, based in England. Respondents reported changes in ways of working due to redeployment, staff shortages, and home working. Widespread adoption of virtual working practices led to concerns of negative impacts. Perceived excessive workload impacted on care with two-thirds of the sample (57, 67%) reporting they had been unable to provide the same quality of care to patients. Impacts on nurses' health and wellbeing were reported with two-thirds of the sample (56, 66%) reporting a deterioration in emotional wellbeing and mental health. Coping mechanisms employed included online team support to share experiences and increased uptake of exercise; however, impacts on lifestyle and access to coping mechanisms varied. Conclusion: Nurses have stepped up to the challenges of the pandemic with teamwork and innovation, but pressure arising from the pandemic and high workloads led to negative impacts on wellbeing. The authors have provided recommendations to improve patient care and support the wellbeing of nurses, which will be key to a resilient workforce living with covid-19. Whilst this study focussed on lung cancer and mesothelioma specialists, the findings have wider implications for other cancer specialties.