Hematological Oncology最新文献

Mantle cell lymphoma is a rare type of B-cell lymphoma, which is considered incurable yet treatable. In recent years, the treatment options of mantle cell lymphoma have multiplied, and the focus of treatment is expected to shift from traditional chemoimmunotherapy toward precision medicine. However, this development is hindered by the high costs of targeted therapies. To provide a baseline for future assessment of costs and benefits of new and emerging MCL treatments, we established a predictive simulated model of lifetime treatment trajectories based on a retrospective cohort of chemoimmunotherapy era patients diagnosed and treated between the year 2000 and 2020.

Brentuximab vedotin (BV)-bendamustine (90 or 120 mg/m2 day 1 and 2) every 28 days is an effective treatment for relapsed/refractory Hodgkin lymphoma (R/R HL) but associated to high toxicity especially for elderly patients. We conducted in St Louis Hospital, Paris, between 2015 and 2021 a retrospective single-center analysis of 44 patients with R/R HL treated with one-day BV-bendamustine (120 mg/m2) every 21 days. Sixteen percent of patients were ≥ 60 years old (yo). Seventy-three percent of patients received total number of cycles without interruption nor adaptation. No patient ≥ 70 yo required treatment interruption. Dose adjustment was necessary for 18% of patients. Infusion-related reaction (36%) occurred always at cycle 2 and was the only cause of treatment interruption. One febrile neutropenia, one non-documented septic shock, one pyelonephritis on transplanted kidney and one COVID complicated by cytopenias were reported. Sixteen percent patients presented a peripheral sensory neuropathy, 7% and 4% respectively grade 3–4 neutropenia and thrombocytopenia. Overall response was 84%, with 73% of complete remission. Median progression-free survival was of 19.8 months (95% CI 13.1-NR) and median overall survival was not reached with a median follow-up of 31 months. We suggest that one-day BV-bendamustine (120 mg/m2) ever 21 days is a safe and feasible treatment for R/R HL especially for elderly patients.

Contemporary studies of Bruton tyrosine kinase inhibitor (BTKi) resistance focus on mutations in the B-cell receptor (BCR) pathway, but alternative mechanisms of resistance remain undefined. Here, we sought to identify novel predictive markers of acquired resistance to acalabrutinib, a second-generation BTKi, in patients with chronic lymphocytic leukemia (CLL). Clinical samples from 41 patients with relapsed/refractory or treatment-naive CLL receiving acalabrutinib as part of a clinical trial (NCT02029443) were divided into two groups: those who continued to respond to treatment (NP, n = 23) and those who developed progressive disease on acalabrutinib therapy (PD, n = 18). Peripheral blood mononuclear cells (PBMCs) from the two groups of patients were profiled at baseline (BL) and at a second timepoint (T2) by RNA-seq and flow cytometry. Our findings show a correlation between acquired resistance to acalabrutinib and upregulation of integrin alpha-4 (ITGA4; CD49d), the BCR surface receptor CD79B, and oncogenes such as MYC, LAG3, and MCL1 in CLL cells. High surface expression of CD49d and CD79b prior to acalabrutinib therapy was associated with increased risk of disease progression on acalabrutinib in patients with CLL. When stratified by pretreatment CD49d surface expression, the CD49d^hi group (defined as ≥ 30% CD49d+ cells at baseline) showed reduced acalabrutinib-induced lymphocytosis and higher levels of tumor proliferation markers such as CD38 and Ki-67 compared with the CD49d^lo group (defined as < 30% CD49d+ cells at baseline). In summary, CD49d and CD79b are useful predictive markers for CLL progression on acalabrutinib.

Trial Registration: ClinicalTrials.gov identifier: NCT02029443

18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) parameters have shown a significant prognostic role in relapsed/refractory large B-cell lymphoma (LBCL) patients undergoing CD19-targeted chimeric antigen receptor (CAR) T-cell therapy. While a substantial body of evidence exists on the prognostic value of PET/CT parameters in peri-CAR T setting, data available on the prognostic value of PET/CT parameters following CAR T-cell therapy failure is lacking. Therefore, we sought to analyze the PET/CT scans of LBCL patients who experienced post-CAR T relapsed/progressive disease and subsequently received salvage therapies. Thirty-three LBCL patients who had PET-CT scans done demonstrating post-CAR T failure and then received salvage therapies [as a first salvage modality: RT alone, nine patients; combined modality therapy (CMT), seven patients; systemic therapy (ST) alone, 17 patients] were analyzed. The median follow-up after CAR T-cell infusion was 11.7 months [interquartile range (IQR): 5.1–24.4 months], and the median follow-up after post-CAR T salvage therapy was 7.3 months (IQR: 2.7–19.1 months). The median timeframe for the PET scan showing post-CAR T failure was 2.4 months (IQR: 0.96–5.0 months). On univariable analysis from salvage therapy start date, high metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were associated with inferior overall survival (OS) (Hazard ratio –HR = 8.4, p < 0.0001; HR = 3.2, p = 0.01, respectively). High MTV was associated with a non-significant trend of inferior progression-free survival (PFS) (HR = 3.5, p = 0.09). High maximum standardized uptake value (SUVmax) was not associated with inferior OS or inferior PFS. On multivariable analysis from salvage therapy start date, high MTV (HR = 4.6, 95% CI: 1.5–14.3, p = 0.009) was identified to be an independent prognostic factor for inferior OS. High International Prognostic Index (IPI) (≥ 3) at the time of salvage therapy (HR = 2.5, 95% CI: 1.1–5.6, p = 0.02) was significantly associated with inferior PFS. Our study shows that semiquantitative PET/CT metrics, especially MTV, are significant prognostic indicators of overall survival in this highly refractory population after CAR T-cell therapy failure, potentially refining prognostic and treatment approaches beyond conventional parameters like IPI.