Evaluating Minimal Residual Disease Negativity as a Surrogate Endpoint for Treatment Efficacy in Multiple Myeloma: A Meta‐Analysis of Randomized Controlled Trials

American Journal of Hematology, Journal Year: 2025, Volume and Issue: 100(3), P. 427 - 438

Published: Jan. 9, 2025

This meta-analysis examined the association between minimal residual disease (MRD) negativity and survival outcomes in 15 304 patients with multiple myeloma (MM) enrolled randomized controlled trials published until June 2, 2024. Overall, there was a significant, negative strong MRD odds ratios hazard (β_PFS = -0.20, p < 0.001, β_OS -0.12, 0.023). These associations remained significant for newly diagnosed -0.35, 0.001), they were consistent but not relapsed/refractory -0.06, 0.635). Sustained at 1 year strongly correlated prolonged PFS -0.30, 0.001). In conclusion, this comprehensive supports as surrogate MM.

Language: Английский

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The Burden of Multiple Myeloma in China: Trends from 1990 to 2021 and Forecasts for 2050

Cancer Letters, Journal Year: 2025, Volume and Issue: 611, P. 217440 - 217440

Published: Jan. 2, 2025

Language: Английский

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Guillain-Barré syndrome in patients with multiple myeloma: three cases report and literature review

BMC Neurology, Journal Year: 2025, Volume and Issue: 25(1)

Published: Jan. 24, 2025

Multiple myeloma (MM) with Guillain-Barré syndrome (GBS) is relatively rare, and the specific mechanism still unclear. The previous infection, surgery, medication use may have contributed to occurrence of GBS. bortezomib in patients MM can easily lead peripheral neuropathy, which similar symptoms GBS, making it challenging diagnose Three IgA type experienced lower limb weakness during treatment. Combined lumbar puncture, nerve conduction studies, other tests, diagnosis was confirmed as All three had a history spinal surgery before onset been treated induced neuropathy. Two clear upper respiratory tract infection After treatment intravenous immunoglobulin, one patient died two showed improvement GBS symptoms. Patients often concurrent infections contribute bortezomib-induce neuropathy overlap those misdiagnosis or missed Timely puncture studies help improve prognosis.

Language: Английский

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The mitochondrial protease ClpP is a promising target for multiple myeloma treatment

Biochemical Pharmacology, Journal Year: 2025, Volume and Issue: 236, P. 116855 - 116855

Published: March 5, 2025

Language: Английский

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T‐cell‐based immunotherapies for human immunodeficiency virus patient with relapsed/refractory multiple myeloma: A success story from our clinic

British Journal of Haematology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 29, 2025

Multiple myeloma (MM) is a plasma cell neoplasm that affects approximately one in 50 cancer patients making it the second most common haematological malignancy adult population. Despite significant advances treatment, MM remains an incurable disease, and all will experience relapses.1 Although not considered acquired immune deficiency syndrome (AIDS)-related some studies have found 2.6-fold higher incidence of among HIV (human immunodeficiency virus [HIV])-positive individuals.2-4 Small observational case series suggested distinctive clinico-biological features HIV-positive compared to HIV-negative patients, including younger age, proportion monoclonal IgG protein, lower neutrophil counts, less renal impairment, fewer osteolytic lesions extramedullary disease.5 The introduction combination antiretroviral therapy (cART) has improved function, reduced opportunistic infections decreased HIV-related morbidity mortality. High-dose chemotherapy followed by autologous stem transplantation (ASCT) for with are effective, demonstrating similar overall survival (OS) infection rates patients.6 However, who relapse, there no data on feasibility next-generation anti-myeloma immunotherapies based T cells (NAIT) such as cART (chimeric antigen receptor [CAR] T-cell therapies) or bispecific engagers, HIV-infected individuals frequently excluded from clinical trials establish current practice guidelines. Only few reports demonstrate safety efficacy CAR malignancies.7 A 58-year-old man, diagnosed coinfection chronic hepatitis B 2008, been treated (bictegravir/emtricitabine/tenofovir alafenamide) since 2019, maintaining undetectable viral load both viruses. he had persistent CD4+ lymphopenia (<250/μL), but infections. In August 2020, was lambda light chain MM, Revised International Staging System (R-ISS) stage 2 (no high-risk karyotype abnormalities, lactate dehydrogenase albumin within normal ranges, serum β2-microglobulin >5.4 mg/L). initial presentation disease included acute kidney injury 3, which required replacement 12 days, hypercalcaemia, multiple bone normocytic anaemia. patient received six cycles bortezomib, cyclophosphamide dexamethasone ASCT standard care at time, resulting complete response. Osteolytic were key relapses over following 3 years. five classes routinely used drugs (Table 1). AKI Ratio K/L < 0.01 plasmacytoma sixth rib = 0.046 Isolated 0.012 Slight increase size (9 × 3.4 cm) 0.004 Net exceeding 10 cm long axis 0.02 Decrease plasmocytoma 1 Consolidation VI: idecabtagene vicleucel referred our clinic July 2023. Given rapidly progressing penta-refractory patient, we decided treat this vicleucel. CD4 (CD4: 114/μL, CD8: 359/μL), leukapheresis successfully performed, yielding good harvesting results (CD4—1.57 107/kg, CD8—4.6 107/kg). We initiated bridging bendamustine–ixazomib dexamethasone. Unfortunately, experienced progression after cycle then use elranatamab bridge administered irradiation costal better local control. During dose escalation, developed grade II cytokine release syndrome, favourably single tocilizumab. After months therapy, chest imaging revealed regression plasmacytoma, positron emission tomography (PET) scans showed absence hypermetabolism. infectious complications febrile aplasia rhinovirus lasted month. respiratory symptomatic did require oxygen support. Due recurrence infections, immunoparesis (with gammaglobulin levels <1 g/L) (nadir CD4: 40/μL), monthly intravenous human polyvalent immunoglobulin (IVIG) infusions addition Bactrim Zelitrex, primary prophylaxis. injection schedule adjusted every weeks starting 2. By end remission, hypermetabolism PET normalization blood levels. To achieve durable 21 days last administration elranatamab, infusion 348.92 106 cells, recommended 300 cells. This preceded 3-day regimen lymphodepletion fludarabine cyclophosphamide, 48-h washout period. treatment well-tolerated, serious side effects observed. monitored clinically, biologically radiologically month, 6 (M12) CAR-T infusion. Follow-up evaluations conducted up M12 post-treatment, results: remission confirmed scan, free ([FLC] below mg/L) peak reached day 9, progressive decrease than 0.1% total months. At months, persistently low lymphocyte levels, count 630/μL 100/μL other cytopenia. prophylactic IVIG substitution until post-CAR develop any during discontinuing substitution. He maintains cART. evaluation cytopenia, 1550/μL 300/μL. For long-term follow-up, scheduled medical visits tests—specifically FLC assessment—every scan planned Limited cases focusing indicate more aggressive course, inadequate response induction shorter progression-free OS, despite well-controlled cART.8 this, none pivotal approval NAIT relapsed/refractory (RRMM) even though experts advocate trial eligibility patients.9 According Abecma marketing authorisation guidance documents, active eligible manufacturing.10 Considering wide array drugs, potential negative interactions could arise. newer generations ART becoming increasingly safer. example, integrase inhibitor bictegravir does interact treatments, unlike reverse transcriptase inhibitors, contraindicated high doses impact ABECMA construct, produced using self-replicating-incompetent lentiviral vector, unknown. first-generation HIV-1 raltegravir promotes DNA damage-induced apoptosis vitro.11 protease nelfinavir shown sensitize proteasome inhibitors overcome resistance vitro.12 phase I study involving bortezomib yielded results.13 highlights successful management RRMM heavily pretreated harvest manufacturing outcomes, abnormal CD4/CD8 ratio. memory activation status determine anti-B-cell maturation (BCMA) therapy. analysed immunophenotype apheresis-derived myelome anti-BCMA Responding enriched population naïve central CD8 precursor cells.14 disequilibrium compartment caused affect NAIT. excellent response, very tolerance manageable complications, regularly monitored, contrasts report cytomegalovirus retinitis, fungal enteritis varicella zoster reactivation BCMA therapy.15 It crucial include studies, significantly their life expectancy, bringing closer general All authors listed manuscript substantially contributed work. SM, LR, FM designed experiment, interpreted wrote manuscript; ABanet, AC, NS, ABonnin, SS, RB, LS, SI, ZVdW EB participated writing. No conflicts interest disclose. original data, contact: [email protected].

Language: Английский

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Macrofocal multiple myeloma in the era of novel agents in China

Therapeutic Advances in Hematology, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 1, 2025

Background: Macrofocal multiple myeloma (MFMM) is characterized by clonal plasma cells comprising less than 20% of the bone marrow, lytic lesions, and absence anemia, renal insufficiency, hypercalcemia. This subtype (MM) has a relatively low incidence. Prognostic staging cytogenetic guidance for MFMM are often insufficient due to tumor burden in marrow. Large cohort studies on this subgroup during era novel agents limited. Objectives: We aim describe clinical characteristics prognostic markers patients undergoing treatment with agents. Methods: Consecutive cases MM diagnosed at Peking University People’s Hospital Fu Xing Capital Medical from 2011 2023 were screened. A propensity score matching was conducted 2:1 ratio, classic based variables age year diagnosis. Results: identified 91 (4%) 182 matched among 2291 patients. The had higher proportion male patients, those <90% marrow multiparameter flow cytometry, extramedullary disease, along lower high-risk cytogenetics or advanced disease staging. demonstrated better overall responses compared control ( p = 0.027) not receiving upfront autologous stem cell transplantation (ASCT). During median follow-up 42.8 months entire cohort, exhibited significantly superior progression-free survival (PFS) (OS) cohort. In multivariate analysis exposure immunomodulatory drugs ASCT consolidation frontline therapy independently associated improved PFS OS. For Ki-67 index ⩾20% inferior PFS, providing valuable information group where inadequate. Conclusion: concluded that strategies should align standard MM, biopsy samples plasmacytoma PFS.

Language: Английский

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Lactoferrin-Derived Peptide Chimera Induces Caspase-Independent Cell Death in Multiple Myeloma

Cells, Journal Year: 2025, Volume and Issue: 14(3), P. 217 - 217

Published: Feb. 3, 2025

Lactoferrin-derived peptide chimera is a synthetic that mimics the functional unit of lactoferrin with antibacterial activity. Although LF has anticancer effects, to best our knowledge, its effects on multiple myeloma have not yet been studied. We explored potential lactoferrin-derived for treatment, malignant clonal plasma cell bone marrow disease. The effectively inhibited MM1S, MM1R, and RPMI8226 growth, induced early late phases apoptosis, but in normal peripheral blood mononuclear cells. Furthermore, modulates relative expression genes involved survival, mitochondrial dysfunction at transcriptional level. Mitochondrial analysis revealed triggered oxidative stress cells, leading reactive oxygen species generation decline membrane potential, resulting dysfunction. did cause caspase-dependent death, it nuclear translocation apoptosis-inducing factor endonuclease G, indicating initiation caspase-independent apoptosis. Overall, induces programmed death lines by increasing factor/endonuclease G. Therefore, cancer therapies.

Language: Английский

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Efficacy and Prognostic Indicators of Isatuximab, Pomalidomide, and Dexamethasone (IsaPd) in Daratumumab‐Refractory Multiple Myeloma Patients: A Multicenter Real‐World Study

Hematological Oncology, Journal Year: 2025, Volume and Issue: 43(2)

Published: Feb. 3, 2025

ABSTRACT This multicenter real‐world analysis evaluated the efficacy of isatuximab, pomalidomide, and dexamethasone (IsaPd) in 51 patients with multiple myeloma (MM) who were refractory to daratumumab (Dara‐R). The majority under 70 years old (60.8%), predominantly female (56.9%), heavily pretreated, 74.5% being triple‐class (TCR); 32.1% 28 cytogenetic data had high‐risk abnormalities. overall response rate (ORR) was 56.9%, including 3 stringent complete (sCR), 4 CR, 7 very good partial (VGPR). Neither age, number prior therapies, TCR status, nor time from Dara refractoriness IsaPd initiation significantly affected rates. Median progression‐free survival (PFS) 5.8 months, a 12‐month PFS probability 30.6%. Baseline hemoglobin (Hb) levels key predictor PFS: Hb < 11.8 g/L 3.5‐fold increased risk progression, median 4.6 months compared 22 those higher Hb. (OS) 21.0 OS 63.4%. Lower (< 11 g/L) associated tenfold mortality. Among underwent FISH analysis, while no significant difference mortality observed, abnormalities exhibited nearly disease progression. These results suggest that offers meaningful option for Dara‐R patients, serving as critical both OS. However, remains modest, underscoring need novel combination therapies.

Language: Английский

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COMMD3 Regulates Copper Metabolism via the ATOX1-ATP7A-LOX Axis to Promote Multiple Myeloma Progression

Biomedicines, Journal Year: 2025, Volume and Issue: 13(2), P. 351 - 351

Published: Feb. 4, 2025

Background: Multiple myeloma (MM) is a hematologic malignancy characterized by the clonal proliferation of plasma cells, with extramedullary (EMM) being an aggressive form involving malignant infiltration beyond bone marrow. Copper metabolism essential for tumor and metastasis, copper MURR1 domain (COMMD) proteins regulating these processes maintaining homeostasis. Dysregulated homeostasis contributes to cancer progression, including MM, elevated levels linked disease aggressiveness poor prognosis. This study investigates role COMMD3 in mediating MM cell particularly its influence on metabolism. Methods: Comprehensive bioinformatics analyses were conducted marrow samples determine expression COMMD3, which was validated through vitro vivo functional assays. The lines RPMI8226 MM1S underwent lentiviral transfection overexpression knockdown. RNA sequencing knockdown cells identify differentially expressed genes. Functional assays measured proliferation, migration, apoptosis, metabolism, non-obese diabetic severe combined immune-deficiency gamma (NSG) mouse xenograft model providing validation. Results: Elevated correlated prognosis patients. promoted modulating intracellular levels, likely ATOX1-ATP7A-LOX copper-metabolism-related pathway. High ATOX1 worse outcomes, inhibition abolished COMMD3’s effects. Conclusions: highlights pivotal via axis. These findings provide insights into EMM mechanisms position as potential therapeutic target. Future research needed validate larger clinical cohorts unravel precise molecular interactions between proteins.

Language: Английский

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T Cell Therapies (TIL, CAR T, TCR)

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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