Search Results (177)

FMC63-CAR T cell therapy targeting CD19 protein on malignant B-cells is effective in patients with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL), with complete response rates of 43–54%. Common germline variants of the immune-checkpoint regulator CTLA-4 may elicit different responses to CAR-T cell therapy. The CTLA4 gene single-nucleotide polymorphism rs231775 coding threonine or alanine at amino acid position 17 of the CTLA-4 protein was prevalent in 55% of the studied DLBCL patients. In a retrospective comparative analysis of clinical outcome, there were significant differences in CTLA4 A17hom vs. T17Ahet and T17hom carriers with four-year progression-free survival at 77%, 59%, and 30% (p = 0.019), four-year overall survival was 79%, 41%, and 33% (p = 0.049), the relapse rates were 20%, 37%, and 56% (p = 0.025), and the death rates 20%, 54%, and 52% (p = 0.049). Conclusions: CTLA4 rs231775 polymorphism may impact the treatment outcome in FMC63-anti-CD19 CAR-T cell therapy, with an association of the CTLA4 minor allele A17 to favorable treatment outcome. Full article

Quantitative ¹⁸F-FDG PET/CT-derived metabolic metrics are strongly associated with patient outcomes in diffuse large B-cell lymphoma (DLBCL), but the lack of consensus on optimal segmentation thresholds limits standardization. This study evaluated the prognostic value of various metabolic tumor volume (MTV) segmentation approaches in 140 stage II–IV DLBCL patients treated with standard immunochemotherapy. MTV was derived using fixed SUV (≥2.5, ≥4.0), relative (>41% SUVmax), and adaptive (liver-to-background) thresholds. Baseline MTV metrics significantly correlated with 3-year overall survival (OS3) in univariate analysis in overall cohort, with MTV41 showing the strongest association (HR: 1.27; p = 0.003). MTV25 and MTV41 remained significant in the stage 4 patient subgroup. However, in multivariate analysis, no MTV metric independently predicted OS3 when adjusted for the International Prognostic Index (IPI), which remained the dominant predictor (HR: 1.95; p < 0.0001). ROC analysis confirmed superior AUC for IPI (0.76) over PET-based metrics (0.64–0.69). Predictive models integrating IPI with PET metrics were robust but failed to improve prognostic accuracy beyond IPI alone. Although PET-derived MTV metrics provide prognostic value in univariate analysis, threshold selection has minimal impact, and their added value is limited when combined with IPI, reinforcing its role as the most reliable survival predictor in DLBCL. Full article

Objective: Early diagnosis and treatment of metastatic pericardial disease are crucial to prevent the life-threatening complication of cardiac tamponade. Thin Layer Cytology (TLC), a widely adopted technique in cytology, has gained significant acceptance for most specimens. Our study aimed to assess the utility of TLC in diagnosing metastatic neoplasms and their origins in pericardial effusions, as well as monitoring response to chemotherapy. Methods: We examined 184 pericardial fluids collected by pericardiocentesis and processed using the ThinPrep liquid-based technique. Various immunocytochemical markers were used to determine the site of metastatic neoplasms. We also evaluated the response to therapy in 53 patients with lung and breast cancer. Results: Out of 184 specimens, 113 pericardial fluids were diagnosed as positive for malignancy, while 71 were negative. Twenty-three cases of unknown primary site were included in the total positive cases. Ninety cases positive for malignancy had a known primary site of origin, including 31 lung carcinomas, 22 breast carcinomas, 10 ovarian carcinomas, 6 T-cell lymphomas, 3 urinary bladder carcinomas, 4 renal carcinomas, 5 adenocarcinomas of the colon, 5 prostate carcinomas, 2 parotid adenocarcinomas, and 2 melanomas. Regarding the 53 cases with chemotherapy treatment, the cytologic examination of pericardial fluid showed a remarkable reduction in neoplastic burden after the third dose of cisplatin or thiotepa instilled into the pericardial cavity. ThinPrep provided excellent preservation of cytomorphological features, high cellularity per slide, and a clear background. This comprehensive analysis provides crucial information about the types and distribution of cancerous cells present in the samples. Conclusions: Thin Layer Cytology (TLC) is a valuable diagnostic tool for detecting metastatic pericardial malignancy. It allows the examination of exfoliated cells from the pericardial fluid, providing crucial information for diagnosis, management, and monitoring the acute responsiveness to intrapericardial chemotherapy. Immunocytochemistry (IHC) can identify specific markers for various types of cancer, enabling a more accurate diagnosis and guiding further treatment decisions. Full article

Background: Allogeneic hematopoietic cell transplant (alloHCT) is a curative option for relapsed/refractory B-cell lymphomas (BCLs), but its role in the evolving field of cellular therapy is increasingly unclear as recent advances in transplant procedures have improved outcomes. Methods: This retrospective, single-center study included 55 BCL patients (large B-cell lymphoma—LBCL; indolent BCL; and mantle cell lymphoma—MCL) treated with alloHCT from 2015 to 2023 at Hôpital Maisonneuve-Rosemont. Primary endpoints were overall survival (OS) and progression-free survival (PFS); secondary endpoints included NRM and GVHD incidence. Results: A total of 55 patients were included (25 LBCLs, 16 indolent BCLs, 14 MCLs), and 76% of LBCLs were of indolent origin (Richter transformation, transformed follicular lymphoma). After a median follow-up of 6.1, 5.8 and 2.4 years for LBCLs, indolent BCLs and MCLs, their 5-year PFS and OS were 57.2% (IC 95%: 34.2–74.7) and 62.8% (IC 95%: 37.9–80.0), 81.2% (IC 95%: 52.5–93.5) and 93.8% (IC 95%: 63.2–99.1), and 39.0% (IC 95%: 14.3–63.3) and 68.1% (IC 95%: 35.4–86.8), respectively. The 5-year NRM was 16.9% (IC 95%: 8.2–28.3) with a relapse incidence of 23.4%. Overall/grade 3–4 acute GVHD occurred in 43.6% and 18.1% of patients. At 3 years, overall/moderate or severe chronic GVHD incidence was 49% and 34.5%. Conclusions: AlloHCT remains a potentially curative option and should be considered for fit patients with chemosensitive FL or LBCLs of indolent origin and a low comorbidity index. Full article

Osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), is widely used in treating patients with EGFR-mutated non-small-cell lung cancers (NSCLCs), especially in cases with secondary resistance mutations. However, tertiary resistance mutations often arise, and there is currently no established standard of care for NSCLC harboring triple EGFR mutations. In recent years, brigatinib, an anaplastic lymphoma kinase (ALK) TKI, has shown effectiveness in treating EGFR triple-mutated NSCLC. Despite this, the combined use of osimertinib and brigatinib remains largely unstudied. This case report describes a 51-year-old woman with EGFR-mutated NSCLC who was initially treated with first- and second-generation EGFR TKIs, then switched to osimertinib upon development of an exon 20 T790M mutation. When an exon 20 C797S mutation emerged, the decision was made to add brigatinib to the osimertinib regimen. The combined treatment of osimertinib and brigatinib offers a promising new approach. Nonetheless, it is important to consider the potential risk of off-target toxicities. Full article

Patient-reported outcome measures (PROMs) are often used to evaluate the impact of treatment and clinical decisions on the patient experience for patients with lymphoma. Regulatory agencies have provided guidance on the use of PROMs for patient-focused drug development. Though PROMs are increasingly utilized, the way in which they are used, analyzed, and reported is heterogeneous. This systematic evidence-based review will focus on how PROMs are currently used for patients with lymphoma, what domains PROMs measure, their clinical significance, links to clinical outcomes, and what gaps need to be filled to better incorporate PROMs as endpoints in clinical trials and clinical decision-making. Full article

This case report highlights the management of a delayed bronchopleural fistula (BPF) following salvage pulmonary resection to achieve local control and no radiographic evidence of disease in a patient treated with serial tyrosine kinase inhibitors (TKIs) for stage IV anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC). The initial pulmonary resection was complicated by dense adhesions and an abnormally torturous pulmonary artery. Six weeks after the index surgery, the patient presented with a delayed BPF requiring decortication, repair of airway, and coverage of the bronchial stump with a serratus anterior muscle flap. Full article

The association between breast cancer and non-Hodgkin lymphoma of the spleen is extremely rare, with very few cases documented in the medical literature. We present the case of a 39-year-old woman in good health but with a family history of breast cancer, who, in 2017, developed invasive lobular carcinoma in her right breast, which was treated with mastectomy followed by hormonal therapy. In 2024, she presented with a suspicious right axillary mass, suspected of recurrence, which was confirmed by fine-needle aspiration biopsy. The patient received neoadjuvant chemotherapy, followed by axillary lymph node dissection and bilateral adnexectomy. CT and PET scans showed suspicious splenic lesions suggestive of metastases. Infectious and hematological tests were negative, leading to the decision to perform laparoscopic splenectomy. Histological examination revealed follicular B-cell non-Hodgkin lymphoma. The patient is now in good general condition and is on a biannual follow-up. The case highlights the diagnostic complexity of tumor recurrences and the need to consider alternative diagnoses other than metastasis in oncological patients. Full article

One challenge of chimeric antigen receptor T-cell therapy (CAR-T) for relapsed or refractory large B-cell lymphoma (LBCL) is achieving disease control during manufacturing. We report real-word outcomes of 100 patients treated with axicabtagene ciloleucel (axi-cel, n = 50) or tisagenlecleucel (tisa-cel, n = 50) at our center. Most patients received bridging therapy (BT) with 48 undergoing radiation BT (RBT) and 32 receiving systemic BT (SBT). The best overall response rate (ORR) was 84% (78% complete response (CR)) for axi-cel and 60% (42% CR) for tisa-cel. At a median follow-up of 16 months, 12-month progression-free survival (PFS) and overall survival (OS) were 72% and 82% for axi-cel, compared to 35% and 57% for tisa-cel. By the bridging approach, 12-month PFS was 60% with RBT, 59% without BT and 35% with SBT (p = 0.06). Notably, axi-cel patients without lymphoma progression during manufacturing (n = 24) achieved 12-month PFS and OS rates of 91% and 96%, respectively. Axi-cel was associated with more cytokine release syndrome (92% vs. 66%, p = 0.003) and neurotoxicity (all-grade 56% vs. 10%, p < 0.001, grade ≥ 328% vs. 4%, p = 0.002). Multivariate analysis identified RBT as independently associated with improved PFS (HR 0.46, 95% CI 0.22–0.96). Pending prospective validation, RBT shows promise for improving CAR-T outcomes in LBCL. Full article

CAR-T cell therapy has significantly improved outcomes for patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), but challenges such as limited resources, manufacturing timelines, and notable toxicities persist. Bispecific antibodies (BsAbs), including glofitamab and epcoritamab, have demonstrated promising efficacy and represent a new treatment option in patients who are unsuitable for or have relapsed following CAR-T therapy. Bispecific antibodies have a manageable safety profile and are generally more widely accessible than CAR-T cell therapy. Case discussions in this paper illustrate the potential real-world application of BsAbs, highlighting their role in treating patients who have relapsed after or are unable to undergo CAR-T cell therapy. Overall, glofitamab and epcoritamab represent valuable treatment options in the evolving landscape of R/R DLBCL. Full article

Lymphomas represent a heterogeneous group of blood tumors, generally divided into non-Hodgkin lymphoma (NHL) (90% of all lymphomas) and Hodgkin lymphoma (HL). High-grade NHL can rapidly progress so that new strategies and potentially therapeutical options are needed. Recently, it was shown that Vitamin D (VitD) inhibits the growth of cancer cells, controls their invasion and metastasis, and strengthens the antitumor activity of various types of chemotherapeutic anticancer agents. Therefore, we reviewed the recent literature about the influence of VitD and its analogues (VDAs) on the treatment and the prognosis of B-cell lymphomas. As to the in vitro studies in different cell lines, VitD3 and VDAs enhanced the anti-proliferative efficacy of various chemotherapeutics and increased the expression of VitD receptor. In in vivo studies, blood levels of VitD were considered: higher values of plasma bioavailable VitD were correlated with better progression-free survival (PFS) and overall survival (OS), while an unfavorable PFS and OS were observed in VitD deficient groups. No clinical trial was made on the analogs, thus confirming the absence of in vivo positive role of these synthetic drugs. In conclusion, higher levels of circulating VitD are related to improved OS, reduced cancer-specific mortality, and better disease-free survival. VitD and analogs showed also positive effects in in vitro studies, while only VitD was able to improve clinical parameters. Furthermore, a complex approach with plant-based diet, adequate levels for motor exercise, and/or eventual VitD supplementation could be a valuable strategy to challenge lymphomas. Full article

Background: The aim of this study was to evaluate real-world clinical outcomes and transplant-related complications of allogeneic stem cell transplantation (alloSCT) for Hodgkin lymphoma (HL). Methods: This was a single-centre, retrospective analysis of relapsed and refractory (R/R) HL patients who received an alloSCT between 1 January 2016 and 29 February 2024 in Hamilton, Ontario. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS), non-relapse mortality (NRM), and graft-versus-host disease/relapse-free survival (GRFS). Results: Twenty-one patients were identified, with thirteen (62%) pre-treated with programmed death 1 (PD-1) blockade with either nivolumab or pembrolizumab. Seventeen (81%) patients underwent related haploidentical donor transplants, while four (19%) patients received a matched unrelated donor transplant. The 2-year OS and PFS rates were 79% (95% CI: 53–92%) and 63% (95% CI: 37–81%), respectively. Trends towards improved OS, PFS, NRM, and GRFS in PD-1-inhibitor-exposed patients were observed. All PD-1-inhibitor-exposed patients who were in complete remission proceeding to alloSCT remained alive at the last follow-up visit. Among the nine patients in partial remission at the time of alloSCT, three deaths were reported, with a 2-year OS of 61%. Conclusions: Our outcome data of a single-centre, heavily pre-treated cohort of Canadian patients confirm that alloSCT with post-transplant cyclophosphamide-based immunosuppression, which has been associated with improvements in PFS, remains a safe and feasible treatment option for patients with R/R HL in the era of checkpoint inhibitor use. Full article

The treatment landscape for patients with advanced ALK-positive NSCLC has rapidly evolved following the approval of several ALK TKIs in Canada. However, public funding of ALK TKIs is mostly limited to the first line treatment setting. Using linked provincial health administrative databases, we examined real-world outcomes of patients with advanced ALK-positive NSCLC receiving ALK TKIs in Ontario between 1 January 2012 and 31 December 2021. Demographic, clinical characteristics and treatment patterns were summarized using descriptive statistics. Kaplan–Meier analysis was performed to evaluate progression-free survival (PFS) and overall survival (OS) among the treatment groups. A total of 413 patients were identified. Patients were administered alectinib (n = 154), crizotinib (n = 80), or palliative-intent chemotherapy (n = 55) in the first-line treatment. There was a significant difference in first-line PFS between the treatment groups. The median PFS (mPFS) was not reached for alectinib (95% CI, 568 days—not reached), compared to 8.2 months (95% CI, 171–294 days) for crizotinib (HR = 0.34, p < 0.0001) and 2.4 months (95% CI, 65–100 days) for chemotherapy (HR = 0.14, p < 0.0001). There was no significant difference in first-line OS between the treatment groups. In patients who received more than one line of treatment, there was a significant difference in mOS between patients who received two or more lines of ALK TKIs compared to those who received one line of ALK TKI (mOS = 55 months (95% CI, 400–987 days) and 26 months (95% CI, 1448–2644 days), respectively, HR = 4.64, p < 0.0001). This study confirms the effectiveness of ALK TKIs in real-world practice and supports the potential benefit of multiple lines of ALK TKI on overall survival in patients with ALK-positive NSCLC. Full article

Nova Scotia (NS) began offering CAR T-cell therapy as a third-line standard of care for eligible patients with relapsed or refractory large B-cell lymphoma (r/r LBCL) in 2022. Recipients of CAR T-cell therapy often experience acute toxicities, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), which require close monitoring and prompt management. This retrospective review aimed to describe the characteristics of adult patients with r/r LBCL deemed eligible to receive CAR T-cell therapy with axicabtagene ciloleucel in NS between January 2022 and June 2024, the toxicities experienced and toxicity management, hospital visits and intensive care unit (ICU) admissions, the utilization of toxicity management guidelines, and general efficacy outcomes. Twenty-seven patients received axicabtagene ciloleucel. All patients experienced CRS (7.4% grade ≥ 3), and 55.6% developed ICANS (25.9% grade ≥ 3). The median hospital stay was 18 days, with 40.7% requiring ICU admission. There was one treatment-related mortality. Most CRS (85.2%) and ICANS (80.0%) cases were managed according to the guidelines. By day +100, the best objective response rate was 81.5% (44.4% complete responses). Patients who received CAR T-cell therapy in NS, Canada, experienced comparable toxicities and efficacy to those reported in pivotal clinical trials and other real-world experiences. Full article