Background: B-cell maturation antigen (BCMA) directed therapies have transformed the treatment landscape for relapsed or refractory multiple myeloma (RRMM). Soluble BCMA (sBCMA), a circulating product of the membrane-bound BCMA shedding, has emerged as a potential biomarker reflecting tumor burden and disease biology. This systematic review and meta-analysis aimed to evaluate the prognostic value of baseline circulating sBCMA in patients with multiple myeloma receiving BCMA-directed therapies, with progression-free survival (PFS) as the primary endpoint. Methods: A systematic literature search of PubMed/MEDLINE, Embase, Scopus, and Web of Science databases was conducted in accordance with PRISMA guidelines. Studies enrolling patients with multiple myeloma treated with BCMA-directed therapies and reporting baseline circulating sBCMA measured in serum or plasma in relation to survival outcomes were included. Hazard ratios (HRs) for PFS and overall survival (OS) were pooled using random-effects models. Risk of bias was assessed using the QUIPS tool. Results: Four independent RRMM cohorts fulfilled the eligibility criteria and were included in the quantitative PFS meta-analysis. Elevated baseline circulating sBCMA was significantly associated with inferior PFS (pooled HR = 2.64, p < 0.05), with a consistent adverse prognostic direction across all studies. Moderate to substantial heterogeneity was observed (I² = 63.2%), potentially reflecting differences in BCMA-directed therapy modalities across cohorts and methodological variability, including study-specific sBCMA cut-off definitions, assay procedures and sampling timepoints. Exploratory subgroup analysis suggested that the prognostic impact of baseline sBCMA on PFS may differ according to BCMA-directed therapy class. Overall risk of bias was judged as low to moderate. Conclusions: Elevated baseline circulating sBCMA is associated with inferior progression-free survival in patients with multiple myeloma treated with BCMA-directed therapies. These findings support the prognostic relevance of sBCMA as a risk stratification marker, although harmonization of assays and cut-offs and prospective validation are required before clinical implementation.

Background: Chronic lymphocytic leukemia (CLL) is a prevalent hematologic malignancy that predominantly affects elderly individuals, posing significant clinical challenges due to patient comorbidities and inherent resistance to conventional chemotherapy. The emergence of targeted therapies combining venetoclax, a selective inhibitor of the anti-apoptotic protein BCL-2, with anti-CD20 monoclonal antibodies has dramatically transformed the treatment landscape. Methods: This retrospective observational study analyzed the differential impacts of first-line venetoclax-obinutuzumab (VenO) and second-line venetoclax-rituximab (VenR) on immunoglobulin G (IgG) levels and absolute neutrophil count (ANC) in CLL patients. Results: Our findings indicate that during first-line VenO therapy, a significant improvement in ANC levels from baseline was observed, whereas patients undergoing second-line VenR therapy demonstrated limited impact on ANC and the decreasing tendency in IgG levels. Patients treated with VenR had a longer disease history and previous exposure to other treatment regimens, primarily chemoimmunotherapy, which could negatively influence immune recovery, making direct comparisons between these two treatment lines challenging. Although this observational study did not directly compare infection rates, the observed enhancement of ANC levels in patients receiving VenO suggests a potential for lower infection risk compared to pretreated VenR patients. Conclusions: These results underscore the clinical significance of considering both the treatment line and the patient’s prior therapeutic history when selecting venetoclax-based regimens for CLL. The potential association of first-line VenO with improved immunological parameters and the complex impact of prior therapies on immunological recovery with second-line VenR warrant further prospective investigation into the correlation between treatment regimen, patient history, immune function, and infectious complications.

Introduction: Anti-CD38-based quadruplets such as daratumumab-bortezomib-lenalidomide-dexamethasone (D-VRd) or daratumumab-bortezomib-thalidomide-dexamethasone (D-VTd), where lenalidomide is not reimbursed, are the internationally recommended first-line treatment for transplant-eligible myeloma. There is ongoing debate about whether anti-CD38 exposure impairs stem cell collection. Most studies compare daratumumab-containing with non-daratumumab induction whilst keeping the mobilisation strategy constant. None have compared two mobilisation agents against each other in both daratumumab-exposed and daratumumab-naïve patients. Methods: We reviewed 66 patients (22 received Ara-C, 44 received CY) who were mobilised at a single centre in Poland between 2018 and 2024. No patients received plerixafor. Results: Patients who were mobilised with Ara-C collected more CD34+ cells than those who received CY, with a median of 12.6 (IQR 9.1–15.9) versus 7.7 (4.9–12.1) ×10⁶/kg (p=0.005), with comparable apheresis sessions. Previous D-VTd treatment did not reduce the overall yield (p=0.43). The benefit of Ara-C persisted in the D-VTd subgroup, despite heavy confounding between induction and mobilisation choice. Discussion: This is the first direct comparison of Ara-C and CY in the daratumumab era. Ara-C-based mobilisation was associated with higher CD34+ yields than CY in a plerixafor-free setting. The apparent advantage in D-VTd-treated patients is exploratory and requires prospective confirmation.