Blood Advances, Journal Year: 2023, Volume and Issue: 7(21), P. 6767 - 6770
Published: Aug. 30, 2023
Language: Английский
Nature Medicine, Journal Year: 2023, Volume and Issue: 29(9), P. 2259 - 2267
Published: Aug. 15, 2023
Elranatamab is a humanized B-cell maturation antigen (BCMA)-CD3 bispecific antibody. In the ongoing phase 2 MagnetisMM-3 trial, patients with relapsed or refractory multiple myeloma received subcutaneous elranatamab once weekly after two step-up priming doses. After six cycles, persistent responders switched to biweekly dosing. Results from cohort A, which enrolled without prior BCMA-directed therapy (n = 123) are reported. The primary endpoint of confirmed objective response rate (ORR) by blinded independent central review was met an ORR 61.0% (75/123); 35.0% ≥complete response. Fifty dosing, and 40 (80.0%) improved maintained their for ≥6 months. With median follow-up 14.7 months, duration response, progression-free survival overall (secondary endpoints) have not been reached. Fifteen-month rates were 71.5%, 50.9% 56.7%, respectively. Common adverse events (any grade; grade 3-4) included infections (69.9%, 39.8%), cytokine release syndrome (57.7%, 0%), anemia (48.8%, 37.4%), neutropenia 48.8%). 3-4 decreased 58.6% 46.6%. induced deep durable responses manageable safety profile. Switching dosing may improve long-term compromising efficacy. ClinicalTrials.gov identifier: NCT04649359 .
Language: Английский
Citations
255
Nature Reviews Disease Primers, Journal Year: 2024, Volume and Issue: 10(1)
Published: June 27, 2024
Language: Английский
Citations
46
Blood Advances, Journal Year: 2023, Volume and Issue: 8(1), P. 194 - 206
Published: Dec. 5, 2023
Teclistamab and other B-cell maturation antigen (BCMA)-targeting bispecific antibodies (BsAbs) have substantial activity in patients with heavily pretreated multiple myeloma (MM) but are associated a high rate of infections. BCMA is also expressed on normal plasma cells mature B cells, which essential for the generation humoral immune response. The aim this study was to improve understanding impact BCMA-targeting BsAbs immunity. teclistamab polyclonal immunoglobulins cell counts evaluated MM who received once-weekly 1.5 mg/kg subcutaneously. Vaccination responses were assessed subset patients. Teclistamabinduced rapid depletion peripheral blood eliminated ex vivo assays. In addition, reduced levels (immunoglobulin G [IgG], IgA, IgE, IgM), without recovery over time while receiving therapy. Furthermore, response vaccines against Streptococcus pneumoniae, Haemophilus influenzae type B, severe acute respiratory syndrome coronavirus 2 severely impaired treated compared vaccination observed newly diagnosed or relapsed/refractory MM. Intravenous immunoglobulin (IVIG) use significantly lower risk serious infections among (cumulative incidence at 6 months: 5.3% IVIG vs 54.8% observation only [P < .001]). conclusion, our data show defects immunity induced by teclistamab, can be mitigated supplementation. This trial registered www.ClinicalTrials.gov as #NCT04557098.
Language: Английский
Citations
32
American Journal of Hematology, Journal Year: 2024, Volume and Issue: 99(3), P. 396 - 407
Published: Jan. 31, 2024
Abstract The use of lenalidomide in frontline therapy for patients with newly diagnosed multiple myeloma (MM) has increased the number those who become refractory to at second line. In this context, we assessed efficacy daratumumab combination ixazomib and dexamethasone (Dara‐Ixa‐dex) prospective phase 2 study DARIA. Eligible had relapsed/refractory MM (RRMM) after one prior line a lenalidomide‐based regimen. primary endpoint was overall response rate (ORR). Secondary endpoints included survival outcomes, safety changes biomarkers bone metabolism. Overall, 50 were enrolled (median age 69 years, 56% males). 32 (64%) lenalidomide, 17 (34%) undergone autologous transplant. ORR 64% ( n = 32); whereas very good partial or better. median time first 1.0 month. After follow‐up 23.4 months, PFS OS 8.1 39.2 respectively. Furthermore, significant markers metabolism became evident as early 6 months on treatment. Regarding safety, 21 (42%) ≥1 grade 3/4 adverse event (AE); most common thrombocytopenia 9, 18%). 14 (28%) serious AE (SAE), being acute kidney injury pneumonia 2, each). Four died due infections. conclusion, second‐line treatment Dara‐Ixa‐dex RRMM pre‐treated regimen resulted rapid responses along favorable effect
Language: Английский
Citations
5
International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(14), P. 11829 - 11829
Published: July 23, 2023
B-cell maturation antigen (BCMA) is a promising therapeutic target for multiple myeloma (MM). The aim of this study was to assess the effectiveness and tolerability monotherapy with conjugated anti-BCMA monoclonal antibody belantamab mafodotin in triple-class refractory patients MM real-world practice. Patients at least one proteasome inhibitor, immunomodulatory drug, anti-CD38 received 2.5 mg/kg intravenously every 3 weeks. Overall, 27 median age 65 years (range 41-81) were included. Of these, 52% male number prior lines treatment 5 (4-10). overall response rate (partial or better) 52%, whereas disease control (stable 70%. progression-free survival (PFS) 2 months (95%CI: 0-7), PFS among responders 12 6-18). Regarding toxicity profile, most common eye toxicity, 44% patients. Keratopathy grade 2-3 reported 33.3% In conclusion, showed safety efficacy profile consistent results registrational study. Importantly, heavily pretreated who responded derived substantial benefit.
Language: Английский
Citations
11
Vaccines, Journal Year: 2024, Volume and Issue: 12(5), P. 518 - 518
Published: May 9, 2024
Patients with multiple myeloma (MM) are a heterogenous, immunocompromised group increased risk for COVID-19 morbidity and mortality but impaired responses to primary mRNA SARS-CoV-2 vaccination. The effects of booster vaccinations breakthrough infections (BTIs) on antibody (Ab) levels cross-protection variants concern (VOCs) are, however, not sufficiently evaluated. Therefore, we analysed humoral cellular vaccine in MM patients stratified according disease stage/treatment into (1) monoclonal gammopathy undetermined significance, (2) after stem cell transplant (SCT) without immunotherapy (IT), (3) SCT IT, (4) progressed MM, healthy subjects (prospective cohort study). In contrast hu-1-specific Ab levels, Omicron-specific Abs their cross-neutralisation capacity remained low even three doses majority patients. particular, receiving anti-CD38 mAb those IT were responders showed delayed formation spike-specific B memory cells. However, hybrid immunity (i.e., vaccination infection) had improved against VOCs, yet the absence severe disease. Our results indicate that require frequent variant-adapted and/or changes other formulations/platforms, which might have similar immunological as BTIs.
Language: Английский
Citations
4
Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)
Published: Jan. 26, 2025
Immunotherapy is a significant risk factor for severe COVID-19 in multiple myeloma (MM) patients. Understanding how immunotherapies lead to crucial improving patient outcomes. Human protein microarrays were used examine the expression of 440 molecules MM patients treated with bispecific T-cell engagers (BiTe) (n = 9), anti-CD38 monoclonal antibodies (mAbs) 10), and proteasome inhibitor (PI)-based regimens 10). Differentially expressed proteins (DEPs) identified analyzed using bioinformatics. BiTe therapy was associated higher incidence COVID-19. We 21 29 DEPs between mAbs group, PI-based respectively, along 25 PI groups. Principal component analysis clustering showed distinct profiles Gene Ontology (GO) revealed that groups related cytokine activity leukocyte migration. Kyoto Encyclopedia Genes Genomes (KEGG) these enriched cytokine-cytokine receptor interaction JAK-STAT signaling pathways. Leukemia inhibitory (LIF) most correlated other thus may play key role both pathways, level LIF highest group. linked due an inflammatory storm, pathway playing roles. Targeting help reduce BiTe.
Language: Английский
Citations
0
Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16
Published: Feb. 18, 2025
The stability of immune responses to SARS-CoV-2 vaccines, especially concerning the cross-reactive recognition Omicron variant, remains incompletely characterized in multiple myeloma (MM) patients. This study evaluated humoral 29 MM patients and cellular a subset 19 patients, specific Wuhan spike proteins, between 16 26 weeks following third vaccine dose. After weeks, we highlighted significant reduction neutralizing antibodies both spikes percentages IFN-γ+CD107a+ spike-specific CD8+ T cells. On other hand, who underwent an additional stimulation two time points, through either fourth dose or breakthrough infection, showed increase stable levels cytotoxic Additionally, those with only three doses experienced higher rate infections during 32-week follow-up period. These findings underscore waning vaccine-induced immunity over may help benefit-risk evaluation vaccination strategies
Language: Английский
Citations
0
Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 14
Published: Feb. 21, 2025
Background and aim Patients diagnosed with cancer, particularly those hematologic malignancies, frequently exhibit a state of immunosuppression. Currently, there remains scarcity dependable biomarkers for assessing the severity COVID-19 in individuals malignancies. We conducted retrospective study morbidity mortality patients hematological malignancies (HM) who had contracted COVID-19. The was to offer reference clinical diagnosis treatment. Methods A total 71 HM-confirmed were enrolled from December 2022 May 2023. Clinical symptoms, laboratory findings, treatment approaches collected documented. classified into survival death groups based on their outcomes, statistical analysis performed data both groups. Results Among patients, 57 (80.3%) alive, 14 (19.7%) died. mean age group significantly higher than that (51.29 ± 20.76 vs . 49.47 13.04, P=0.030). proportion receiving mechanical ventilation (P<0.001). rate critically severe compared mild, moderate, Correlation revealed certain indicators lactic acid dehydrogenase (LDH), albumin (ALB), creatine kinase (CK), troponin T (TnT), N-terminal pro-brain natriuretic peptide (NT-proBNP) fibrin degradation product (FDP), which exhibited significant differences between groups, correlated COVID-19-related (all P<0.05). Cox proportional hazards model indicated LDH an independent risk factor associated prognosis Conclusion suffer due infection. may serve as Monitoring variations levels can assist healthcare providers evaluating disease progression, adjusting plans timely manner, predicting patient outcomes.
Language: Английский
Citations
0
Bone Marrow Transplantation, Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 21, 2025
Patients with relapsed or refractory multiple myeloma (R/R-MM) are more susceptible to develop severe coronavirus disease 2019 (COVID-19) for their immunocompromised states. Despite good responses B-cell maturation antigen (BCMA)-targeted chimeric receptor (CAR)-T cell therapy, deficiencies in humoral immunity following CAR-T infusions can still cause life-threatening complications these patients. We conducted a comparative study delineate the clinical characteristics and outcomes between recipients of BCMA-targeted therapy who contracted COVID-19 vs. unaffected counterparts. Advanced age (odds ratio [OR] = 1.367, 95% confidence interval [CI] 1.017–1.838, P 0.038) was risk factor developing COVID-19, while complete remission (CR) achieved by (OR 0.012, CI 0.000–0.674, 0.032) protective. Male sex (hazard [HR] 5.274, 1.584–17.562, 0.007) CR (HR 3.107, 1.025–9.418, 0.045) were protective factors associated duration. 0.064, 0.007–0.589, 0.015) also OS, progression at time diagnosis 14.206, 1.555–129.819, 0.019) regarded as factor. Thus, older patients R/R-MM those do not achieve after should be most protected from infection Omicron variant.
Language: Английский
Citations
0