المؤلفون: Solves, Pilar, Bataller, Ana, Gálvez, Ana Belén, Asensi Cantó, Pedro, Santiago, Marta, Moreno, María José, Gómez-Seguí, Inés, de la Rubia, Javier

المصدر: Hemato; Jun2024, Vol. 5 Issue 2, p109-114, 6p

مستخلص: Background: Selective IgA deficiency (IgA-D) has been historically considered a high-risk entity for developing allergic/anaphylactic reactions after blood transfusion (AATRs). However, it has been suggested that the IgA-D-related anaphylactic transfusion reaction is not evidence-based. Methods: We conducted three different approaches to collect evidence about epidemiology, AATRs, and transfusion management of patients with IgA-D at La Fe University Hospital. Firstly, we analysed the prevalence of IgA-D in a population of patients diagnosed with acute leukaemia, The second approach consisted of collecting transfusion data from IgA-D patients. Finally, we reviewed the IgA levels of patients recorded in the hemovigilance system suffering an AATR. Results: IgA-D prevalence was 1 in 334 patients. At least one blood component was transfused to 23 patients diagnosed with IgA-D. Plasma was transfused to eight IgA-D patients, while six patients received red blood cells, platelets, and plasma. No adverse reactions were reported in any patient. AATRs occurred in 325 men and 264 women with a median age of 52 years. Severe reactions occurred in 56 patients (1/14,520 components). Mean IgA levels were 215 mg/dL (4–5570) for mild reactions and 214 mg/dL (14–824) for severe reactions (p = ns). Washed platelets were administered to two patients who developed severe and repeated AATRs. Both had normal IgA levels. Conclusions: Since the AATRs related to IgA-D are extremely low, as reported in current hemovigilance systems, IgA-D should not be considered a high-risk entity to develop AATRs. On the contrary, our findings support standard transfusion management of IgA-D patients. [ABSTRACT FROM AUTHOR]

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المؤلفون: de la Rubia, Javier^1,2 (AUTHOR) delarubia_jav@gva.es, Alonso, Rafael³ (AUTHOR), Clavero, María Esther⁴ (AUTHOR), Askari, Elham⁵ (AUTHOR), García, Alfonso⁶ (AUTHOR), Antón, Cristina⁷ (AUTHOR), Fernández, Margarita⁸ (AUTHOR), Escalante, Fernando⁹ (AUTHOR), García, Ana¹⁰ (AUTHOR), Rios-Tamayo, Rafael¹¹ (AUTHOR), Conesa, Venancio¹² (AUTHOR), Bermúdez, María Arancha¹³ (AUTHOR), Merchán, Beatriz¹⁴ (AUTHOR), Velasco, Alberto E.¹⁵ (AUTHOR), Blanchard, María Jesús¹⁶ (AUTHOR), Sampol, Antonia¹⁷ (AUTHOR), Gainza, Eukene¹⁸ (AUTHOR), Hernández, Prisma Montserrat¹⁹ (AUTHOR), Alegre, Adrián²⁰ (AUTHOR)

المصدر: Cancers. Jun2023, Vol. 15 Issue 11, p2964. 13p.

مصطلحات موضوعية: *THERAPEUTIC use of immunoglobulins, *RESEARCH, *SCIENTIFIC observation, *CONFIDENCE intervals, *IMMUNOGLOBULINS, *OPTIC nerve diseases, *CANCER relapse, *INVESTIGATIONAL drugs, *CELL receptors, *RETROSPECTIVE studies, *ACQUISITION of data, *TREATMENT effectiveness, *COMPARATIVE studies, *MEDICAL records, *DESCRIPTIVE statistics, *MULTIPLE myeloma, *PROGRESSION-free survival, *PATIENT safety, *OVERALL survival, *DISEASE risk factors

مصطلحات جغرافية: SPAIN

مستخلص: Simple Summary: Patients with multiple myeloma (MM) who become refractory to three or more lines of therapy (RRMM patients) have few valid therapeutic alternatives. Among them, drugs directed against the BCMA antigen expressed in plasma cells are very appealing. Belantamab-mafodotin (belamaf) is the first antibody-drug conjugate against BCMA ready for clinical use. In this paper, we report the Spanish experience of belamaf monotherapy in 156 patients with RRMM. The overall response rate was 41.8%, with 39.8% of patients achieving a partial response or better. Median progression-free survival was 3.61 months, but interestingly, it increased to 14.47 months in patients achieving a minimal response or better. Treatment was well tolerated, ocular events being the most reported toxicity (87.9%; grade ≥ 3, 33.7%), but only two patients discontinued treatment due to side effects. Overall, our results confirm the safety and efficacy of belamaf in this poor prognosis subset of patients. Belantamab-mafodotin (belamaf) is a novel antibody-drug conjugate targeting B-cell maturation antigen that showed anti-myeloma activity in patients with relapsed and refractory multiple myeloma (RRMM). We performed an observational, retrospective, and multicenter study aimed to assess the efficacy and safety of single-agent belamaf in 156 Spanish patients with RRMM. The median number of prior therapy lines was 5 (range, 1–10), and 88% of patients were triple-class refractory. Median follow-up was 10.9 months (range, 1–28.6). The overall response rate was 41.8% (≥CR 13.5%, VGPR 9%, PR 17.3%, MR 2%). The median progression-free survival was 3.61 months (95% CI, 2.1–5.1) and 14.47 months (95% CI, 7.91–21.04) in patients achieving at least MR (p < 0.001). Median overall survival in the entire cohort and in patients with MR or better was 11.05 months (95% CI, 8.7–13.3) and 23.35 (NA-NA) months, respectively (p < 0.001). Corneal events (87.9%; grade ≥ 3, 33.7%) were the most commonly adverse events, while thrombocytopenia and infections occurred in 15.4% and 15% of patients, respectively. Two (1.3%) patients discontinued treatment permanently due to ocular toxicity. Belamaf showed a noticeably anti-myeloma activity in this real-life series of patients, particularly among those achieving MR or better. The safety profile was manageable and consistent with prior studies. [ABSTRACT FROM AUTHOR]

المؤلفون: Solves, Pilar, Marco-Ayala, Javier, Sanz, Miguel Ángel, Gómez-Seguí, Inés, Balaguer-Roselló, Aitana, Facal, Ana, Villalba, Marta, Montoro, Juan, Sanz, Guillermo, de la Rubia, Javier, Sanz, Jaime

المصدر: Journal of Clinical Medicine; May2023, Vol. 12 Issue 10, p3467, 10p

مصطلحات موضوعية: HEMATOPOIETIC stem cell transplantation, CORD blood transplantation, BLOOD transfusion

مستخلص: Introduction: Transfusion plays a main role in supportive treatment for patients who receive an allogeneic hematopoietic stem cell transplantation (HSCT). In this study, we compare the transfusion requirements of patients undergoing different modalities of HSCT according to different time periods. The objective is to assess the evolution of HSCT transfusion requirements over time, from a single institution. Methods: The clinical charts and transfusion records of patients who underwent HSCT of different modalities at La Fe University Hospital during a twelve-year period were reviewed (2009–2020). For analysis, we divided the overall time into three periods: 1 from 2009 to 2012, 2 from 2013 to 2016 and 3 from 2017 to 2020. The study included 855 consecutive adult HSCT: 358 HLA-matched related donors (MRD), 134 HLA-matched unrelated donors (MUD), 223 umbilical cord blood transplantation (UCBT) and 140 haploidentical transplants (Haplo-HSCT). Results: There were no significant differences in RBC and PLT requirements or transfusion independence among the three time periods for MUD and Haplo-HSCT. However, the transfusion burden increased significantly for MRD HSCT during the 2017–2020 period. Conclusion: despite HSCT modalities having evolved and changed over time, overall transfusion requirements have not significantly decreased and continue to be a cornerstone of transplantation-supportive care. [ABSTRACT FROM AUTHOR]

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المؤلفون: Rosa-Rosa, Juan Manuel, Cuenca, Isabel, Medina, Alejandro, Vázquez, Iria, Sánchez-delaCruz, Andrea, Buenache, Natalia, Sánchez, Ricardo, Jiménez, Cristina, Rosiñol, Laura, Gutiérrez, Norma C., Ruiz-Heredia, Yanira, Barrio, Santiago, Oriol, Albert, Martin-Ramos, Maria-Luisa, Blanchard, María-Jesús, Ayala, Rosa, Ríos-Tamayo, Rafael, Sureda, Anna, Hernández, Miguel-Teodoro, de la Rubia, Javier

المصدر: Cancers; Oct2022, Vol. 14 Issue 20, p5169-N.PAG, 13p

مصطلحات موضوعية: DRUG efficacy, SEQUENCE analysis, GENETIC mutation, PREDICTIVE tests, SINGLE nucleotide polymorphisms, KARYOTYPES, CANCER patients, CHROMOSOME abnormalities, FLUORESCENCE in situ hybridization, GENOMICS, DESCRIPTIVE statistics, MULTIPLE myeloma, TUMOR markers, PROGRESSION-free survival

مستخلص: Simple Summary: Multiple Myeloma (MM) is considered an incurable chronic disease, which prognosis depends on the presence of different genomic alterations. To accomplish a complete molecular diagnosis in a single essay, we have designed and validated a capture-based NGS approach to reliably identify pathogenic mutations (SNVs and indels), genomic alterations (CNVs and chromosomic translocations), and IGH rearrangements. We have observed a good correlation of the results obtained using our capture panel with data obtained by both FISH and WES techniques. In this study, the molecular classification performed using our approach was significantly associated with the stratification and outcome of MM patients. Additionally, this panel has been proven to detect specific IGH rearrangements that could be used as biomarkers in patient follow-ups through minimal residual disease (MRD) assays. In conclusion, we think that MM patients could benefit from the use of this capture-based NGS approach with a more accurate, single-essay molecular diagnosis. Next-generation sequencing (NGS) has greatly improved our ability to detect the genomic aberrations occurring in multiple myeloma (MM); however, its transfer to routine clinical labs and its validation in clinical trials remains to be established. We designed a capture-based NGS targeted panel to identify, in a single assay, known genetic alterations for the prognostic stratification of MM. The NGS panel was designed for the simultaneous study of single nucleotide and copy number variations, insertions and deletions, chromosomal translocations and V(D)J rearrangements. The panel was validated using a cohort of 149 MM patients enrolled in the GEM2012MENOS65 clinical trial. The results showed great global accuracy, with positive and negative predictive values close to 90% when compared with available data from fluorescence in situ hybridization and whole-exome sequencing. While the treatments used in the clinical trial showed high efficacy, patients defined as high-risk by the panel had shorter progression-free survival (p = 0.0015). As expected, the mutational status of TP53 was significant in predicting patient outcomes (p = 0.021). The NGS panel also efficiently detected clonal IGH rearrangements in 81% of patients. In conclusion, molecular karyotyping using a targeted NGS panel can identify relevant prognostic chromosomal abnormalities and translocations for the clinical management of MM patients. [ABSTRACT FROM AUTHOR]

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المؤلفون: Solana-Altabella, Antonio, Megías-Vericat, Juan Eduardo, Ballesta-López, Octavio, Boluda, Blanca, Cano, Isabel, Acuña-Cruz, Evelyn, Rodríguez-Veiga, Rebeca, Torres-Miñana, Laura, Sargas, Claudia, Sanz, Miguel Á., Borrell-García, Carmela, López-Briz, Eduardo, Poveda-Andrés, José Luis, De la Rubia, Javier, Montesinos, Pau, Martínez-Cuadrón, David

المصدر: Cancers; Apr2022, Vol. 14 Issue 8, p1921, 10p

مصطلحات موضوعية: CANCER chemotherapy, RETROSPECTIVE studies, ACQUISITION of data, MEDICAL care costs, MEDICAL care use, CANCER patients, HEALTH insurance reimbursement, MEDICAL records, HOSPITAL care, DESCRIPTIVE statistics, HEMATOPOIETIC stem cell transplantation

مصطلحات جغرافية: SPAIN

مستخلص: Simple Summary: Studies addressing the economic costs and burden of secondary acute myeloid leukemia (sAML) are scarce in the literature. We analyzed this topic in a real-life population of sAML patients between 60–75 years receiving intensive chemotherapy induction. In elderly patients with sAML and intensive regimens, it entails an increase in costs and a longer hospital stay. In these specific patients, almost a third of the time is spent hospitalized after the diagnosis of sAML. There are no studies with this type of population and diagnosis, which gives added value to the results obtained. Pharmacoeconomic studies in patients with AML are being carried out due to the need to evaluate the cost-effectiveness of new oral drugs, therapeutic schemes with higher costs than previous treatments. Background: Information regarding the impact on healthcare systems of secondary acute myeloid leukemia (sAML) is scarce. Methods: A retrospective review of medical charts identified patients aged 60–75 years with sAML between 2010 and 2019. Patient information was collected from diagnosis to death or last follow-up. Outpatient resource use, reimbursement, frequency and duration of hospitalization, and transfusion burden were assessed. Forty-six patients with a median age of 64 years were included. Anthracycline plus cytarabine regimens were the most common induction treatment (39 patients, 85%). The ratio of the total days hospitalized between the total follow-up was 29%, with a sum of 204 hospitalizations (average four/patient; average duration 21 days). The total average reimbursement was EUR 90,008 per patient, with the majority (EUR 77,827) related to hospital admissions (EUR 17,403/hospitalization). Most hospitalizations (163, mean 22 days) occurred in the period before the first allogeneic hematopoietic stem cell transplant (alloHSCT), costing EUR 59,698 per patient and EUR 15,857 per hospitalization. The period after alloHSCT (in only 10 patients) had 41 hospitalizations (mean 21 days), and a mean reimbursement cost of EUR 99,542 per patient and EUR 24,278 per hospitalization. In conclusion, there is a high consumption of economic and healthcare resources in elderly patients with sAML receiving active treatments in Spain. [ABSTRACT FROM AUTHOR]

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المؤلفون: Puig, Noemí, Corchete-Sánchez, Luis A., Pérez-Morán, José J., Dávila, Julio, Paíno, Teresa, de la Rubia, Javier, Oriol, Albert, Martín-Sánchez, Jesús, de Arriba, Felipe, Bladé, Joan, Blanchard, María-Jesús, González-Calle, Verónica, García-Sanz, Ramón, Paiva, Bruno, Lahuerta, Juan-José, San-Miguel, Jesús F., Mateos, María-Victoria, Ocio, Enrique M.

المصدر: Cancers; Dec2020, Vol. 12 Issue 12, p3615, 1p

مصطلحات موضوعية: THERAPEUTIC use of monoclonal antibodies, CLINICAL trials, DIARRHEA, DRUG efficacy, FLOW cytometry, IMMUNOTHERAPY, KILLER cells, MEMBRANE proteins, MONOCLONAL antibodies, MULTIPLE myeloma, MUSCLE proteins, T cells, TUMOR markers, PROGRAMMED cell death 1 receptors, IMMUNE checkpoint inhibitors, CHEMICAL inhibitors, THERAPEUTICS

مستخلص: Simple Summary: Multiple myeloma patients with persistent disease after treatment show increased expression of PDL1 in tumor plasma cells and of PD1 in T lymphocytes. This suggests a role of the PD1/PDL1 axis in treatment failure that could potentially be reverted with pembrolizumab, an anti-PD1 monoclonal antibody. The GEM-Pembresid trial enrolled 20 patients with multiple myeloma achieving a suboptimal response to the previous treatment that received intravenous pembrolizumab every 3 weeks with the objective of eradicating the residual disease. Pembrolizumab was acceptably well tolerated in the 17 patients evaluable for safety, but no improvement in the baseline responses was documented. Although no determinants of response could be identified, we detected a lower expression of PD1/PDL1 in a subgroup of patients progressing in the first 4 months after enrollment; furthermore, a reduction in the percentage of NK cells induced by pembrolizumab was observed. PD1 expression in CD4⁺ and CD8⁺ T cells is increased after treatment in multiple myeloma patients with persistent disease. The GEM-Pembresid trial analyzed the efficacy and safety of pembrolizumab as consolidation in patients achieving at least very good partial response but with persistent measurable disease after first- or second-line treatment. Moreover, the characteristics of the immune system were investigated to identify potential biomarkers of response to pembrolizumab. One out of the 17 evaluable patients showed a decrease in the amount of M-protein, although a potential late effect of high-dose melphalan could not be ruled out. Fourteen adverse events were considered related to pembrolizumab, two of which (G3 diarrhea and G2 pneumonitis) prompted treatment discontinuation and all resolving without sequelae. Interestingly, pembrolizumab induced a decrease in the percentage of NK cells at cycle 3, due to the reduction of the circulating and adaptive subsets (0.615 vs. 0.43, p = 0.007; 1.12 vs. 0.86, p = 0.02). In the early progressors, a significantly lower expression of PD1 in CD8⁺ effector memory T cells (MFI 1327 vs. 926, p = 0.03) was observed. In conclusion, pembrolizumab used as consolidation monotherapy shows an acceptable toxicity profile but did not improve responses in this MM patient population. The trial was registered at clinicaltrials.gov with identifier NCT02636010 and with EUDRACT number 2015-003359-23. [ABSTRACT FROM AUTHOR]

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المؤلفون: Legarda, Mario A., Cejalvo, María J., de la Rubia, Javier

المصدر: Cancers; Dec2020, Vol. 12 Issue 12, p3576, 1p

مصطلحات موضوعية: MULTIPLE myeloma treatment, CANCER patients, DRUG therapy, CLINICAL trials, HEMATOPOIETIC stem cell transplantation, IMMUNOTHERAPY, MEDICAL technology, DRUG approval, EARLY diagnosis

مستخلص: Simple Summary: The evolving data from trials assessing novel combinations as a part of the frontline and relapse treatment in transplant and non-transplant candidates have markedly improved the anti-myeloma efficacy of the different therapeutic regimens and improved patients' prognosis. Current treatment objectives are focused to further improve the rate of complete remission, time to progression, progression-free survival and overall survival without increasing toxicity. Besides, different strategies are being developed in the elderly population as this group of patients requires a closer monitoring with individualized, dose-modified regimens to improve tolerability while maintaining their quality of life. This article presents a general description of the novelties of the whole treatment of multiple myeloma; from induction in the newly diagnosed patient through the role of hematopoietic stem cell transplantation and maintenance treatment until early and late relapses; including a section on recently approved drugs as well as novel drugs and immunotherapy in advanced stages of research. In the past 20 years, few diseases have seen as great progress in their treatment as multiple myeloma. With the approval of many new drugs and the limited availability of clinical trials comparing head-to-head the different possible combinations, the choice of the best treatments at each stage of the disease becomes complex as well as crucial since multiple myeloma remains incurable. This article presents a general description of the novelties of the whole treatment of multiple myeloma, from induction in the newly diagnosed patient through the role of hematopoietic stem cell transplantation and maintenance treatment until early and late relapses, including a section on recently approved drugs as well as novel drugs and immunotherapy in advanced stages of research, and that will surely play a relevant role in the treatment of this devastating disease in the coming years. [ABSTRACT FROM AUTHOR]

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