Multiple myeloma (MM) is a hematologic disease characterized by the clonal expansion of malignant plasma cells that accumulate in the bone marrow, leading to osteolytic bone disease, hypercalcemia, anemia, and renal dysfunction. Daratumumab was the first monoclonal anti-CD38 antibody approved for the treatment of MM, initially in relapse/refractory settings and, more recently, for newly diagnosed patients. Increased first-line usage of daratumumab will also substantially change treatment approaches for patients with relapsed/refractory disease. Due to the cost and availability of bispecific T cell redirecting antibodies (BsAbs) and chimeric antigen receptor T cell therapy (CAR-T) in real-life settings in many countries, retreatment with daratumumab in subsequent lines of therapy might be a reasonable choice. Data regarding efficacy and optimal combinations of daratumumab retreatment are lacking, and here we provide a short literature review of available data. We identified only a small number of articles based on retrospective analysis of medical records in real-life settings. A strong consistency in results regarding response rates and treatment duration was noticed among mainly heavily pre-treated MM patients, with approximately half of patients achieving at least partial remission (PR) after retreatment with daratumumab-based protocol. The duration of treatment and time to the next treatment for retreatment episodes were considerable and consistent with clinical expectations for later lines of therapy. The analysis of data in this literature review indicates that daratumumab retreatment may provide meaningful clinical benefit to some patients with relapsed/refractory MM despite having prior exposure. However, further research is needed to identify clinical and biological parameters that may predict favorable responses to daratumumab retreatment.
Relapse remains the leading cause of treatment failure after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in acute myeloid leukemia (AML). Early identification of patients at increased post-transplant relapse risk is essential to enable intensified surveillance and pre-emptive therapeutic strategies. Wilms’ tumor 1 (WT1) is overexpressed in most AML cases and represents a broadly applicable molecular marker; however, its utility as a peripheral blood (PB) measurable residual disease (MRD) marker after allo-HSCT remains incompletely defined. In this prospective multicenter cohort study, 43 adults with AML in complete remission underwent allo-HSCT between 2021 and 2023. WT1 expression in PB was quantified using standardized real-time quantitative PCR before transplantation (WT1_pre) and at day +30 (WT1_30). Receiver operating characteristic analysis identified an optimal threshold for relapse prediction. A WT1 cutoff of ≥3 copies/104ABL discriminated relapse risk. WT1_30 demonstrated strong prognostic performance (AUC 0.79; p = 0.005), whereas WT1_pre showed more modest predictive value (AUC 0.69; p = 0.037). Patients with WT1_30 ≥ 3 had inferior 12-month progression-free survival compared with those with WT1_30 < 3 (52.9% vs. 90.9%, p = 0.0059) and a higher 12-month cumulative incidence of relapse (31% vs. 9%, p = 0.054). WT1_pre ≥ 3 was also associated with inferior progression-free and overall survival (both p = 0.0008). Relapsed patients had significantly higher WT1_30 levels than non-relapsed patients (median 5.0 vs. 2.0 copies/104 ABL; p = 0.018). Peripheral blood WT1 expression, particularly at day +30, is associated with an increased relapse risk after allo-HSCT in AML and may support early post-transplant risk stratification. The identified cutoff should be considered exploratory and requires validation in larger independent cohorts.
Hodgkin lymphoma (HL) is a rare lymphoid neoplasm in which Hodgkin/Reed–Stenberg (HRS) cells are admixed with a population of non-neoplastic inflammatory cells and fibrosis. Dysregulated expressions of cell cycle regulators and transcription factors have been proven as one of the hallmarks of HL. In that context, SATB1 and p16 have been reported as potential regulators of HL progression and survival. However, to date, no studies have assessed the expression levels of SATB1 and p16 in HL in Croatian patients or their prognostic values. Therefore, we investigated the expression pattern of SATB1 and p16 in paraffin-embedded lymph node biopsies using standard immunohistochemistry. We found that 21% of the patients stained positive for SATB1, while 15% of the patients displayed positive staining for p16. Furthermore, we aimed to understand the prognostic value of each protein through the analysis of the overall survival (OS) and progression-free survival (PFS). SATB1 showed a significantly positive correlation with better OS and PFS, while p16 expression had no impact. Interestingly, when patients were stratified by a combination of the two studied markers, we found that patients in the SATB1+/p16- group tended to have the best prognosis in HL, according to statistical significance. In conclusion, SATB1 and p16 might be potentially useful as diagnostic and prognostic markers for HL.