dexamethasone (OT502 / IBI10090 / OT 502)

The implantation site as a treatment variable for sustained-release dexamethasone.

Alaçamlı Göksu G, Kaşıkcı Murat M, Kaderli Sema Tamer ST

High efficacy and tolerability of daratumumab-based regimens in first-line treatment of patients with immunoglobulin light-chain amyloidosis: a real-world evidence analysis.

Cui Yajuan Y, Luo Yunya Y, Li Ji J, Yuan Lingli L et al.

Daratumumab was the first monoclonal antibody targeting cluster of differentiation 38 (CD38) to demonstrate high response rates in both untreated and pretreated cases of immunoglobulin light-chain (AL) amyloidosis. We conducted a single-center, retrospective real-world case series to evaluate the efficacy and safety of daratumumab as a first-line treatment option. Daratumumab was administered with bortezomib and dexamethasone (D-Vd), bortezomib, cyclophosphamide, and dexamethasone (D-VCd), or low-dose dexamethasone (Dd). Forty-four patients were eligible, including 14 patients with stage IIIb. By the 6-month milestone (N = 36), 21 (59%) patients achieved at least complete response (CR), 10 (28%) patients achieved very good partial response (VGPR), and 5 (14%) patients achieved partial response (PR). The cardiac response rate was 50% at 3 months, 69% at 6 months, and 84% at 12 months. The renal response rate reached 40% by the 6-month mark. Importantly, hematologic, cardiac, and renal response rates were generally comparable between stage IIIb and non-stage IIIb patients. After a median follow-up of 13 (range 2-45) months, 6 (14%) patients died, all with stage IIIb disease. The median overall survival (OS) was not reached, with a 6-month survival rate of 93% and a 1-year survival rate of 84%. Univariate analysis showed that Mayo stage IIIb, difference between involved and uninvolved free light chains (dFLC) ≥ 300 mg/L, and a time to treatment of more than 12 months were associated with poor overall survival. Lymphocytopenia emerged as the most prevalent hematologic adverse effect, with grade 3-4 lymphocytopenia observed in 32% of patients. Among non-hematologic adverse reactions, infection was observed in 39% of patients. Daratumumab demonstrates significant efficacy in treating newly diagnosed AL amyloidosis, with excellent hematologic and organ response rates, a remarkable safety profile, and favorable tolerability among AL amyloidosis patients. However, early cardiac mortality before responses could manifest underscores that advanced cardiac stage remains an adverse prognostic factor for OS.

Dexamethasone restores odontogenic differentiation in lipopolysaccharide-inflamed human dental pulp stem cells.

DU Yong Y, Yang Yang Y, Lian Hongguang H, Yang Haiyan H et al.

Pulpitis caused by bacterial infection compromises dental pulp regeneration. This study investigated whether dexamethasone (Dex) could restore odontogenic differentiation in lipopolysaccharide (LPS)-inflamed human dental pulp stem cells (hDPSCs) and examined the involvement of TLR4/NF-κB signaling. hDPSCs isolated from healthy third molars were characterized by flow cytometry, and Cell Counting Kit-8 assays were used to identify noncytotoxic concentrations of LPS (2 μg/mL) and Dex (10-8 mol/L). In an LPS-induced inflammatory model, with or without Dex pretreatment, the expression and secretion of proinflammatory cytokines (IL-6, TNF-α, and IL-1β) were quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). TLR4/NF-κB activation was evaluated by qRT-PCR and western blotting, including measurement of total and phosphorylated p65. Odontogenic differentiation was assessed using alkaline phosphatase (ALP) activity and Alizarin Red S (ARS) mineralization assays. Data were analyzed by one-way analysis of variance followed by Tukey's post hoc test. LPS markedly increased cytokine expression and secretion, upregulated TLR4, increased the p-p65/p65 ratio, and reduced ALP activity and mineralized nodule formation. Dex pretreatment significantly attenuated cytokine induction, reduced TLR4 expression and p65 phosphorylation, and restored ALP activity and mineralization relative to LPS alone. Low-dose Dex attenuated LPS-induced inflammation in hDPSCs by suppressing the TLR4/NF-κB axis and restored odontogenic differentiation. These findings support further investigation of localized Dex delivery as an adjunct to vital pulp therapy.

Impact of daratumumab on stem cell collection in patients with AL amyloidosis.

Kauer Joseph J, Dittrich Tobias T, Smeykal Andreas A, Farid Kiavasch M N KMN et al.

Autologous stem cell transplantation following high-dose melphalan is an effective consolidation therapy for the initial treatment of systemic AL amyloidosis. While quadruplet induction therapy involving daratumumab is the standard-of-care, its impact on stem cell yield has not been studied. Furthermore, the relation of stem cell doses and long-term bone marrow function following quadruplet induction therapy remains unclear. It is unknown whether stem cell mobilization with G-CSF and plerixafor is comparable to that achieved with chemotherapy in AL amyloidosis. We analyzed the impact of induction and mobilization regimens on stem cell yield in 180 patients using a prospectively maintained database. Descriptive analyses and multivariable logistic regression analyses were performed for collection outcomes. The primary endpoint was overall stem cell collection yield. The median age at diagnosis was 55 years, with 62% of patients being male. Organ involvement included heart in 48% and kidney in 60% of patients. For induction, 51% of patients received a bortezomib-based regimen (e.g. CyBorD or BorD), 15% received a daratumumab-containing regimen and 27% underwent chemotherapy-free induction therapy. Chemo-free mobilization with G-CSF was performed in 23% of patients, while 39% received cyclophosphamide and dexamethasone (CD) and 33% received cyclophosphamide, adriamycin and dexamethasone (CAD). The total collection after chemo-free mobilization was lower compared to CD and CAD (5.44 × 10⁶ versus 7.29 × 10⁶ versus 9.69 × 10⁶ CD34/kg, p < 0.001). Daratumumab decreased the yield compared to chemotherapy-free induction (5.93 versus 9.24 × 10⁶/kg, p = 0.013) and showed a negative trend compared to bortezomib-based regimen (8.01 × 10⁶/kg, p = 0.147) in univariable analysis. Multivariable logistic regression analysis showed that daratumumab-exposed patients collected stem cell products of > 6.5 × 10⁶/kg less often (Odds ratio (OR) 0.40, p = 0.079). The same was true for patients undergoing mobilization with G-CSF and without plerixafor (OR 0.32, p = 0.012). Stem cell transplantation with > 6.5 × 10⁶/kg might improve short-term and long-term bone marrow function, as reflected by a lower incidence of thrombocytopenia. Mobilization regimens had a stronger impact on stem cell yield than induction therapies. Stem collection is feasible after DaraCyBorD, however, high stem cell doses should be applied to maintain adequate bone marrow function.