Unal Atas

Background: Elranatamab, a bispecific antibody targeting BCMA and CD3, has demonstrated clinical activity in relapsed/refractory multiple myeloma. Real-world evidence regarding infectious complications and supportive care remains limited. We evaluated the early clinical activity, safety profile, infectious complications, and supportive care practices associated with relapsed/refractory multiple myeloma (RRMM). This study represents one of the first multicenter real-world evaluations of elranatamab in Türkiye. Methods: This multicenter retrospective study included 87 patients with relapsed/refractory multiple myeloma treated with elranatamab. Clinical characteristics, treatment responses, immune-mediated toxicities, infectious complications, and supportive care practices were assessed. Overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) were evaluated. Multivariable analyses were performed to identify factors associated with treatment response and clinical outcomes. Results: At 3 months, ORR was 47.1% in the ITT population, 54.7% in the mITT population, and 83.7% among evaluable patients; corresponding 6-month ORRs were 31.0%, 42.2%, and 81.8%, respectively. The high proportion of patients without landmark response assessments primarily reflected insufficient follow-up, early death, or disease progression. Elevated LDH remained independently associated with lower response probability and inferior clinical outcomes. Cytokine release syndrome (CRS) occurred in 69% of patients, with grade ≥ 3 events in 5.7%, whereas immune effector cell-associated neurotoxicity syndrome (ICANS) was infrequent (4.6%) and no grade ≥ 3 events occurred. Grade ≥ 3 infections occurred in 39% of patients, including CMV events requiring antiviral treatment in 24.1%. No HBV reactivation occurred among patients receiving antiviral prophylaxis. Median PFS and OS were 8.1 and 10.6 months, respectively. Conclusions: Elranatamab demonstrated early clinical activity and a manageable safety profile in a heavily pretreated real-world RRMM population. Infectious complications, including CMV events, remained clinically relevant, emphasizing the importance of supportive care. Longer follow-up is needed to characterize long-term outcomes.

Aims: To evaluate the prognostic value of hypogammaglobulinemia at diagnosis in patients with diffuse large B-cell lymphoma (DLBCL) and its association with clinical characteristics and survival outcomes. Methods: A total of 177 adult patients with newly diagnosed DLBCL and available serum immunoglobulin G (IgG) levels were retrospectively analyzed. IgG-defined hypogammaglobulinemia was defined as IgG 1, poor R-IPI score, low albumin levels, presence of B symptoms, bone marrow involvement, and infection during follow-up were associated with inferior survival outcomes. In multivariable analysis, IgG-defined hypogammaglobulinemia was not an independent prognostic factor for PFS but remained independently associated with OS in the model including R-IPI. Conclusion: IgG-defined hypogammaglobulinemia at diagnosis may be associated with inferior survival outcomes in patients with DLBCL. Further prospective multicenter studies are needed to clarify its independent prognostic significance and potential role in risk stratification.

Introduction: Chemotherapy-induced thrombocytopenia (CIT) is a common dose-limiting toxicity that disrupts on-time, full-dose chemotherapy, yet no pharmacologic therapy is formally approved. Growing evidence from randomized and late-phase studies with thrombopoietin receptor agonists (TPO-RAs) has renewed interest in targeted supportive care. We evaluated the effectiveness and safety of eltrombopag for CIT in routine clinical practice. Methods: We conducted a small, retrospective, single-arm multicenter cohort study of 31 adults with solid tumors (74.2% stage IV). Given the descriptive, hypothesis-generating nature of this study, no causal inference regarding efficacy can be drawn. Platelet counts and chemotherapy continuity were tracked from baseline through week 12 after eltrombopag initiation. Bleeding, thrombosis, and laboratory safety signals were recorded. Results: The median platelet count increased from 33 × 10⁹/L at baseline to 71 × 10⁹/L at week 1 and 99.5 × 10⁹/L by week 12. Overall, 18/31 patients (58.1%) resumed chemotherapy within 3 weeks, and 15/31 (48.4%) completed planned regimens by week 6. Adverse events were limited to mild, transient elevations in transaminases (n = 3); no major bleeding or thrombotic events occurred. Conclusions: In this real-world multicenter cohort, eltrombopag was associated with rapid platelet recovery and improved chemotherapy deliverability with an acceptable safety profile. The retrospective, single-arm design and the hypothesis-generating nature of these findings preclude definitive conclusions regarding causal efficacy. These observational data highlight the need for prospective controlled trials to characterize the clinical role, optimal dosing, and long-term safety of oral TPO-RAs in CIT.

We read with great interest the comprehensive review by Bangolo et al

Background Diffuse large B-cell lymphoma (DLBCL) is a biologically heterogeneous lymphoma with variable treatment outcomes. Immune checkpoints are key regulators of tumor-immune interactions and important targets in cancer therapy. This study investigates the roles of PD-1, PD-L1, and CTLA-4 gene polymorphisms, along with their mRNA and protein expression, in DLBCL pathogenesis. Methods This case–control study included 20 patients with newly diagnosed DLBCL and 20 age- and sex-matched healthy controls. SNPs in PD-1 (rs2227981), PD-L1 (rs4143815), and CTLA-4 (rs231775) were genotyped. Gene expression was assessed via RT-qPCR, and protein levels on immune cells were analyzed by flow cytometry. Results PD-1, PD-L1, and CTLA-4 mRNA levels were significantly elevated in DLBCL patients (p = 0.018, p = 0.006, p = 0.031, respectively). These SNPs were associated with expression changes (PD-1: p = 0.009; PD-L1: p = 0.007; CTLA-4: p = 0.018). Flow cytometry showed elevated percentages of CD4⁺PD-1⁺ (p = 0.010) and CD4⁺PD-L1⁺ (p = 0.002) cells in patients. No significant clinical differences were found among DLBCL subtypes. Conclusion These results suggest that overexpression of these checkpoints and related genetic variants may contribute to immune escape and disease progression in DLBCL. PD-1, PD-L1, and CTLA-4 may serve as potential biomarkers for prognosis and personalized therapy. Further large-scale studies are needed to confirm these findings.

Introduction: Elranatamab, a bispecific antibody targeting B-cell maturation antigen (BCMA) and CD3, has demonstrated remarkable efficacy in relapsed or refractory multiple myeloma (RRMM). With the growing clinical use of BCMA-directed bispecific antibodies, their safety profile continues to evolve; however, progressive multifocal leukoencephalopathy (PML) has not been systematically described with elranatamab to date. Case Report: A 67-year-old woman with RRMM achieved a complete response following elranatamab therapy. After the seventh treatment cycle, she developed neurological symptoms including dysarthria and gait disturbance. Brain magnetic resonance imaging revealed multifocal, non-enhancing white-matter lesions, and cerebrospinal fluid polymerase chain reaction confirmed JC virus infection, establishing the diagnosis of PML. Management and Outcome: Elranatamab was discontinued immediately. Despite treatment with intravenous immunoglobulin, mirtazapine, and compassionate-use nivolumab, her neurological status progressively worsened, necessitating intubation and intensive care management. Discussion: This case suggests a probable association between elranatamab therapy and JC virus reactivation leading to PML. The pathogenesis is likely multifactorial, reflecting both prior cumulative immunosuppression and elranatamab-induced plasma-cell depletion with resultant hypogammaglobulinemia. Clinicians should maintain vigilance for new or unexplained neurological manifestations in patients receiving BCMA-directed T-cell–redirecting therapies. Early neuroimaging and cerebrospinal fluid JC virus testing, combined with proactive immunoglobulin replacement and systematic pharmacovigilance, are essential for timely diagnosis and improved outcomes. Overall, this case highlights the need for early JC virus monitoring and awareness of delayed neuroinfectious complications associated with BCMA-targeted immunotherapies.

Background: Renal impairment is a frequent and severe complication of multiple myeloma, most commonly caused by light-chain cast nephropathy. Therapeutic plasma exchange (TPE) has been proposed as an adjunctive approach to rapidly reduce circulating free light chains; however, its clinical benefit remains controversial. Methods: We retrospectively analyzed 71 patients treated between 2013 and 2023, of whom 30 received TPE in addition to anti-myeloma therapy and 41 received anti-myeloma therapy alone. Renal outcomes were assessed within a predefined early treatment window encompassing the first 4–6 cycles of therapy. Renal response was defined as a ≥50% reduction in serum creatinine and/or dialysis independence. Multivariable logistic regression and sensitivity analyses were performed to adjust for baseline imbalances, including renal function and anti-myeloma backbone therapy. Results: Although renal function improved significantly over time in both groups, renal response rates were comparable between patients treated with and without TPE (40% vs. 36.6%). In multivariable analysis, TPE was not independently associated with renal response. Importantly, in a sensitivity analyses restricted to patients receiving bortezomib-based regimens, the addition of TPE remained unassociated with improved renal outcomes. Conclusions: In this real-world cohort, adjunctive TPE did not confer a significant advantage in renal recovery or dialysis independence beyond contemporary anti-myeloma therapy. These findings indicate that renal recovery is predominantly driven by effective anti-myeloma treatment rather than extracorporeal light-chain removal.