Relapsed/refractory primary mediastinal large B-cell lymphoma: a structured review of epidemiology, treatment guidelines and real-world treatment practices

Background: Primary mediastinal (thymic) large B-cell lymphoma (PMBCL) is an uncommon subtype of diffuse large B-cell lymphoma. Approximately 10–30% of patients experience refractory or relapsed PMBCL (rrPMBCL) after first-line therapy. Data and treatment guidelines for rrPMBCL are scarce, and management is based on clinical experience. Methods: Two structured literature reviews were undertaken to determine the incidence, prevalence, and mortality rates associated with rrPMBCL, and to identify clinical practice guidelines and real-world patterns of care. Results: Epidemiology studies included reported lymphomas (n = 1), non-Hodgkin lymphoma (n = 1), lymphoid neoplasm (n = 1), PMBCL (n = 6), and rrPMBCL (n = 1). Of 12 published treatment guidelines, only four provided recommendations for rrPMBCL. Sixteen studies provided data on real-world treatment patterns, but most were single-center studies with small patient numbers. Chemotherapy/immunochemotherapy, followed by high-dose treatment (HDT) and stem cell transplantation, was a mainstay of salvage therapy in most studies; real-world care generally followed treatment guidelines. Conclusions: Salvage chemotherapy (often with rituximab and radiotherapy), followed by HDT and stem cell transplantation, appears to be the standard real-world treatment for rrPMBCL. However, large prospective and retrospective studies are warranted to improve our knowledge of real-world treatment patterns.</p

Pembrolizumab versus the standard of care for relapsed and refractory classical Hodgkin’s lymphoma progressing after brentuximab vedotin: an indirect treatment comparison

<p><b>Background</b>: There is significant unmet need among patients with relapsed and refractory classical Hodgkin’s lymphoma (RRcHL) who have failed multiple lines of therapy, including brentuximab vedotin (BV). Pembrolizumab, an immune checkpoint inhibitor, is one possible treatment solution for this population.</p> <p><b>Research methods</b>: The objective of this study was to compare progression-free survival (PFS) with standard of care (SOC) versus pembrolizumab in previously BV treated RRcHL patients. A systematic literature review identified one observational study of SOC that was suitable for comparison with KEYNOTE-087, the principal trial of pembrolizumab in this population. Both naïve and population-adjusted (using outcomes regression) pairwise indirect comparisons were conducted. The primary analysis included all patients who had failed BV, with a secondary analysis conducted including only those known to have failed BV that was part of definitive treatment.</p> <p><b>Results</b>: In the primary analysis, SOC was inferior to pembrolizumab in both the unadjusted comparison (HR 5.00 [95% confidence interval (CI) 3.56–7.01]) and the adjusted comparison (HR 6.35 [95% CI 4.04–9.98]). These HRs increased to 5.16 (95% CI 3.61–7.38) and 6.56 (95% CI 4.01–10.72), respectively, in the secondary analysis.</p> <p><b>Conclusion</b>: Pembrolizumab offers a significant improvement in PFS compared to SOC in this population.</p

Prussian blue staining of ossicles derived from FePro or unlabeled BMSCs.

<p>Prussian blue (PB) staining of a representative ossicle derived from BMSCs labeled with FePro (A) and control unlabeled BMSCs (B). PB staining of a representative ossicle derived from BMSCs labeled with FePro showing PB⁺ adipocytes (C). PB staining of a representative ossicle derived from labeled BMSCs showing PB⁺ pericytes (D).</p

Global gene expression and multidimensional scaling analysis of FePro labeled BMSCs.

<p>BMSC samples from 3 donors (FePro-labeled, gold nanoparticle-labeled and unlabeled control) and control cells (3 samples from human embryonic stem cells and 3 samples of adult cells) were analyzed by an oligonucleotide microarray. The multidimensional scaling plot similarly grouped the hES cells together, the adult cells other than BMSCs together in another group, and all the BMSC samples into a third group. The BMSCs did not cluster according to the type of labeling method. hES- human embryonic stem cell; adult indicated the adult cells: Fb-fibroblasts, EC endothelial cells, SMC-smooth muscle cells; BMSC-FePro: bone marrow stromal cellslabeled with FePro; BMSC-Gold: bone marrow stromal cells labeled with gold nanoparticle; BMSC-control: unlabeled BMSC control; D1: donor 1; D2-donor 2; D3 donor 3.</p

Dilution of FePro in cultured FePro-labeled and unlabeled BMSCs.

<p>The microphotographs show PB staining of BMSCs cultured <i>in vitro</i> at passages 3, 4, 5 and 6 after BMSCs at passage 2 were labeled with FePro.</p

Immunohistochemical staining of ossicles derived from FePro or GFP labeled and unlabeled BMSCs.

<p>A representative ossicle derived from unlabeled (A) and FePro labeled (B) BMSCs at 8 weeks, stained with H & E showing comparable abundant bone formation and abundant hematopoiesis. Immunohistochemistry staining for GFP of a representative ossicle derived from BMSCs labeled with both FePro and lentivirus carrying GFP (C) and control unlabeled BMSCs (D).</p

CD 146 expression in FePro-labeled BMSCs.

<p>(A) Representative flow cytometry histogram with overlay of the two groups showing no difference in CD146 expression after SPION labeling of BMSCs. (B) Bar graph showing mean CD146 expression in FePro labeled and unlabeled BMSC. Note the lack of statistically significant difference in CD146 expression after SPION labeling (solid colored bars), Student t test, p>0.5. Data shown as mean +/− S.D. of CD 146 expression in 5 donors.</p

Colony forming efficiency in FePro-labeled BMSCs.

<p>Secondary colony forming efficiency of BMSCs plated at clonal density (A) or high density (B) from 5 donors. Data are represented as mean +/− S.D. of colony forming units for each donor done in triplicates. Note the lack of a statistically different change in number of colonies in SPION-labeled BMSCs (solid colored bars), Student t test, p>0.5. A similar lack of a statistically different change in the number of colonies were found when the secondary colony forming efficiency experiments from 5 donors were repeated independently by two other scientists.</p

Pain and analgesic use associated with skeletal-related events in patients with advanced cancer and bone metastases

PURPOSE: Bone metastases secondary to solid tumors increase the risk of skeletal-related events (SREs), including the occurrence of pathological fracture (PF), radiation to bone (RB), surgery to bone (SB), and spinal cord compression (SCC). The aim of this study was to evaluate the impact of SREs on patients' pain, analgesic use, and pain interference with daily functioning. METHODS: Data were combined from patients with solid tumors and bone metastases who received denosumab or zoledronic acid across three identically designed phase 3 trials (N = 5543). Pain severity (worst pain) and pain interference were assessed using the Brief Pain Inventory at baseline and each monthly visit. Analgesic use was quantified using the Analgesic Quantification Algorithm. RESULTS: The proportion of patients with moderate/severe pain and strong opioid use generally increased in the 6 months preceding an SRE and remained elevated, while they remained relatively consistent over time in patients without an SRE. Regression analysis indicated that all SRE types were significantly associated with an increased risk of progression to moderate/severe pain and strong opioid use. PF, RB, and SCC were associated with significantly greater risk of pain interference overall. Results were similar for pain interference with emotional well-being. All SRE types were associated with significantly greater risk of pain interference with physical function. CONCLUSIONS: SREs are associated with increased pain and analgesic use in patients with bone metastases. Treatments that prevent SREs may decrease pain and the need for opioid analgesics and reduce the impact of pain on daily functioning