المؤلفون: Pascual Izquierdo, Cristina, Mingot Castellano, María Eva, Kerguelen Fuentes, Ana E., García-Arroba Peinado, José, Cid, Joan, Moraima Jimenez, Maria, Valcarcel, David, Gómez Seguí, Inés, de la Rubia, Javier, Martin, Paz, Goterris, Rosa, Hernández, Luis, Tallón, Inmaculada, Varea, Sara, Fernández, Marta, García Muñoz, Nadia, Vara, Míriam, Fernández Zarzoso, Miguel, García Candel, Faustino, Paciello, María Liz, García García, Irene, Zalba, Saioa, Campuzano, Verónica, Gala, José María, Vidán Estévez, Julia, Moreno Jiménez, Gemma, López Lorenzo, José Luis, González Arias, Elena, Freiría, Carmen, Solé, María, Ávila Idrovo, Laura Francisca, Hernández Castellet, José Carlos, Cruz, Naylen, Lavilla, Esperanza, Pérez Montaña, Albert, Atucha, Jon Ander, Moreno Beltrán, María Esperanza, Moreno Macías, Juán Ramón, Salinas, Ramón, del Rio Garma, Julio

المصدر: Blood Advances. Vol. 6, nº 24, December 2022, pp. 6219 - 6227

مصطلحات موضوعية: caplacizumab, prednisone, rituximab

الوصف: Immune thrombotic thrombocytopenic purpura (iTTP) is a thrombotic microangiopathy caused by anti-ADAMTS13 antibodies. Caplacizumab is approved for adults with an acute episode of iTTP in conjunction with plasma exchange (PEX) and immunosuppression. The objective of this study was to analyze and compare the safety and efficacy of caplacizumab vs the standard of care and assess the effect of the concomitant use of rituximab. A retrospective study from the Spanish TTP Registry of patients treated with caplacizumab vs those who did not receive it was conducted. A total of 155 patients with iTTP (77 caplacizumab, 78 no caplacizumab) were included. Patients initially treated with caplacizumab had fewer exacerbations (4.5% vs 20.5%; P < .05) and less refractoriness (4.5% vs 14.1%; P < .05) than those who were not treated. Time to clinical response was shorter when caplacizumab was used as initial treatment vs caplacizumab used after refractoriness or exacerbation. The multivariate analysis showed that its use in the first 3 days after PEX was associated with a lower number of PEX (odds ratio, 7.5; CI, 2.3-12.7; P < .05) and days of hospitalization (odds ratio, 11.2; CI, 5.6-16.9; P < .001) compared with standard therapy. There was no difference in time to clinical remission in patients treated with caplacizumab compared with the use of rituximab. No severe adverse event was described in the caplacizumab group. In summary, caplacizumab reduced exacerbations and refractoriness compared with standard of care regimens. When administered within the first 3 days after PEX, it also provided a faster clinical response, reducing hospitalization time and the need for PEX. ; 9 páginas

وصف الملف: application/pdf

العلاقة: http://hdl.handle.net/10498/29789Test

الإتاحة: https://doi.org/10.1182/bloodadvances.2022008028Test
http://hdl.handle.net/10498/29789Test

المؤلفون: Puig, Noemí, Contreras, María Teresa, Agulló, Cristina, Martínez López, Joaquín, Oriol Bosch, Albert, Blanchard, María Jesús, Ríos, Rafael, Martín, Jesús, Iñigo, María Belén, Sureda, Anna, Hernández, Miguel Teodoro, De La Rubia, Javier, González Calle, Verónica, Krsnik, Isabel, Cabañas, Valentín, Palomera, Luis, Moraleda, José María, Bargay, Joan, Cedena, María Teresa, Paiva, Bruno, Rosiñol, Laura, Bladé, J. (Joan), San Miguel, Jesús, Lahuerta, Juan José, Mateos, María Victoria

المصدر: Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

مصطلحات موضوعية: Anticossos monoclonals, Espectrometria de masses, Monoclonal antibodies

الوصف: Monitoring of the monoclonal protein (M-protein) by electrophoresis and/or immunofixation (IFE) has long been used to assess treatment response in multiple myeloma (MM). However, with the use of highly effective therapies, the M-protein becomes frequently undetectable, and more sensitive methods had to be explored. We applied IFE and mass spectrometry (EXENT&FLC-MS) in serum samples from newly diagnosed MM patients enrolled in the PETHEMA/GEM2012MENOS65 obtained at baseline (n = 223), and after induction (n = 183), autologous stem cell transplantation (n = 173), and consolidation (n = 173). At baseline, the isotypes identified with both methods fully matched in 82.1% of samples; in the rest but 2 cases, EXENT&FLC-MS provided additional information to IFE with regards to the M-protein(s). Overall, the results of EXENT&FLC-MS and IFE were concordant in >80% of cases, being most discordances due to EXENT&FLC-MS+ but IFE cases. After consolidation, IFE was not able to discriminate 2 cohorts with different median progression-free survival (PFS), but EXENT&FLC-MS did so; furthermore, among IFE patients, EXENT&FLC-MS identified 2 groups with significantly different median PFS (P = .0008). In conclusion, compared with IFE, EXENT&FLC-MS is more sensitive to detect the M-protein of patients with MM, both at baseline and during treatment, and provides a more accurate prediction of patients' outcome.

وصف الملف: 6 p.; application/pdf

العلاقة: Reproducció del document publicat a: https://doi.org/10.1182/bloodadvances.2021006762Test; Blood Advances, 2022, vol. 6, núm. 11, p. 3234-3239; https://doi.org/10.1182/bloodadvances.2021006762Test; http://hdl.handle.net/2445/188952Test; 9298490

الإتاحة: https://doi.org/10.1182/bloodadvances.2021006762Test
http://hdl.handle.net/2445/188952Test

المؤلفون: Cuker, Adam, Cataland, Spero, Coppo, Paul, de La Rubia, Javier, Friedman, Kenneth, George, James, Knoebl, Paul, Kremer Hovinga, Johanna, Lӓmmle, Bernhard, Matsumoto, Masanori, Pavenski, Katerina, Peyvandi, Flora, Sakai, Kazuya, Sarode, Ravi, Thomas, Mari, Tomiyama, Yoshiaki, Veyradier, Agnès, Westwood, John-Paul, Scully, Marie

المساهمون: Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Recherche clinique appliquée à l'hématologie (URP_3518), Université Paris Cité (UPCité), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal Paris

المصدر: ISSN: 0006-4971.

مصطلحات موضوعية: [SDV]Life Sciences [q-bio]

الوصف: International audience ; Abstract Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a potentially fatal thrombotic microangiopathy caused by autoantibody-mediated severe deficiency of ADAMTS13. Standardized definitions of response, exacerbation, remission, and relapse were initially proposed in 2003 and modified by the International Working Group for TTP in 2017. These definitions, which have been widely used in clinical practice and research, are based primarily on the platelet count and are benchmarked against the timing of discontinuation of therapeutic plasma exchange (TPE). They do not incorporate ADAMTS13 activity or the temporizing effects on the platelet count of caplacizumab, a novel anti–von Willebrand factor (VWF) nanobody. In light of these limitations, the IWG aimed to develop revised consensus outcome definitions that incorporate ADAMTS13 activity and the effects of anti-VWF therapy, by using an estimate-talk-estimate approach. The updated definitions distinguish clinical remission and clinical relapse (defined primarily by platelet count) from ADAMTS13 remission and ADAMTS13 relapse (defined by ADAMTS13 activity). The revised definitions of exacerbation and remission are benchmarked against not only the timing of discontinuation of TPE but also that of anti-VWF therapy. Retrospective validation of the revised definitions is described, although they have yet to be prospectively validated. Clinical implications of the updated outcome definitions are also discussed and an example of their application to clinical practice is provided to highlight their clinical relevance.

العلاقة: hal-03244695; https://hal.science/hal-03244695Test

الإتاحة: https://doi.org/10.1182/blood.2020009150Test
https://hal.science/hal-03244695Test

المؤلفون: Peyvandi, Flora, Cataland, Spero, Scully, Marie, Coppo, Paul, Knoebl, Paul, Kremer Hovinga, Johanna A., Metjian, Ara, de la Rubia, Javier, Pavenski, Katerina, Minkue Mi Edou, Jessica, De Winter, Hilde, Callewaert, Filip

المصدر: Peyvandi, Flora; Cataland, Spero; Scully, Marie; Coppo, Paul; Knoebl, Paul; Kremer Hovinga, Johanna A.; Metjian, Ara; de la Rubia, Javier; Pavenski, Katerina; Minkue Mi Edou, Jessica; De Winter, Hilde; Callewaert, Filip (2021). Caplacizumab prevents refractoriness and mortality in acquired thrombotic thrombocytopenic purpura: integrated analysis. Blood advances, 5(8), pp. 2137-2141. American Society of Hematology 10.1182/bloodadvances.2020001834

مصطلحات موضوعية: 610 Medicine & health

الوصف: The efficacy and safety of caplacizumab in individuals with acquired thrombotic thrombocytopenic purpura (aTTP) have been established in the phase 2 TITAN and phase 3 HERCULES trials. Integrated analysis of data from both trials was conducted to increase statistical power for assessing treatment differences in efficacy and safety outcomes. Caplacizumab was associated with a significant reduction in the number of deaths (0 vs 4; P < .05) and a significantly lower incidence of refractory TTP (0 vs 8; P < .05) vs placebo during the treatment period. Consistent with the individual trials, treatment with caplacizumab resulted in a faster time to platelet count response (hazard ratio, 1.65; P < .001), a 72.6% reduction in the proportion of patients with the composite end point of TTP-related death, TTP exacerbation, or occurrence of at least 1 treatment-emergent major thromboembolic event during the treatment period (13.0% vs 47.3%; P < .001), and a 33.3% reduction in the median number of therapeutic plasma exchange days (5.0 vs 7.5 days) vs placebo. No new safety signals were identified; mild mucocutaneous bleeding was the main safety finding. This integrated analysis provided new evidence that caplacizumab prevents mortality and refractory disease in acquired TTP and strengthened individual trial findings, with a confirmed favorable safety and tolerability profile. These trials were registered at www.clinicaltrials.gov as #NCT01151423 and #NCT02553317.

وصف الملف: application/pdf

العلاقة: https://boris.unibe.ch/156090Test/

الإتاحة: https://doi.org/10.1182/bloodadvances.2020001834Test
https://boris.unibe.ch/156090/1/Caplacizumab_prevents_advancesadv2020001834.pdfTest
https://boris.unibe.ch/156090Test/

المؤلفون: Alonso Sarasquete, María Eugenia, García Sanz, Ramón, Marín Rubio, Luis Alberto, Alcoceba Sánchez, Miguel, Chillón Santos, María del Carmen, Balanzategui, A, Santamaria, Carlos, Rosiñol, Laura, De la Rubia, Javier, Hernandez, Miguel T., Garcia-Navarro, Inmaculada, Lahuerta, Juan José, González Díaz, Marcos, San Miguel Izquierdo, Jesús Fernando

مصطلحات موضوعية: Bisphosphonate, Osteonecrosis of the Jaw, Myeloma, Genetic Polymorphisms, Genetic Predisposition to Disease, Diphosphonates, Jaw Diseases, Multiple Myeloma, Alleles, Haplotypes, Humans, Genome, Osteonecrosis, Aryl Hydrocarbon Hydroxylases, 3205.04 Hematología, alelos, difosfonatos, aril hidrocarburo hidroxilasas, humanos, enfermedades maxilomandibulares, mieloma múltiple, genoma, haplotipos, predisposición genética a la enfermedad

الوصف: Se trata de un descubrimiento de gran originalidad que liga la estructura del gen CYP2C8 y la fisiopatología dentaria como causa de osteonecrosis de mandíbula en pacientes bajo trata-miento con bisfosfonatos. Es uno de los verdaderos avances de la tecnología d SNPs en los denominados GWAS (Genomic Wide Association Studies, o estudios de asociación genética ampliada) ; [EN]We have explored the potential role of genetics in the development of osteonecrosis of the jaw (ONJ) in multiple myeloma (MM) patients under bisphosphonate therapy. A genome-wide association study was performed using 500 568 single nucleotide polymorphisms (SNPs) in 2 series of homogeneously treated MM patients, one with ONJ (22 MM cases) and another without ONJ (65 matched MM controls). Four SNPs (rs1934951, rs1934980, rs1341162, and rs17110453) mapped within the cytochrome P450-2C gene (CYP2C8) showed a different distribution between cases and controls with statistically significant differences (P = 1.07 x 10(-6), P = 4.231 x 10(-6), P = 6.22 x 10(-6), and P = 2.15 x 10(-6), respectively). SNP rs1934951 was significantly associated with a higher risk of ONJ development even after Bonferroni correction (P corrected value = .02). Genotyping results displayed an overrepresentation of the T allele in cases compared with controls (48% vs 12%). Thus, individuals homozygous for the T allele had an increased likelihood of developing ONJ (odds ratio 12.75, 95% confidence interval 3.7-43.5). ; Hospital Universitario de Salamanca Universidad de Salamanca ; Hospital Universitario de Salamanca

العلاقة: https://doi.org/10.1182/blood-2008-04-147884Test; PI06-1354; Red Española de Cancer RD06/0020/0006; IDIBAPS; Sarasquete, M. E., García-Sanz, R., Marin, L., Alcoceba, M., Chillón, M. C., Balanzategui, A., . & San Miguel, J. F. (2008). Bisphosphonate-related osteonecrosis of the jaw is associated with polymorphisms of the cytochrome P450 CYP2C8 in multiple myeloma: a genome-wide single nucleotide polymorphism analysis. Blood, The Journal of the American Society of Hematology, 112(7), 2709-2712. https://doi.org/10.1182/blood-2008-04-147884Test; http://hdl.handle.net/10366/155234Test

الإتاحة: https://doi.org/10.1182/blood-2008-04-147884Test
http://hdl.handle.net/10366/155234Test

المؤلفون: Mateos Manteca, María Victoria, Hernández, José M., Hernández, Miguel T., Gutiérrez Gutiérrez, Norma Carmen, Palomera, Luis, Fuertes, M., Díaz-Mediavilla, Joaquín, Lahuerta, Juan José, De la Rubia, Javier, Terol, María-José, Sureda, Anna, Bargay, Joan, Ribas, Paz, De Arriba, Felipe, Alegre, Adrian, Oriol, Albert, Carrera, Dolores, García-Laraña, José, García Sanz, Ramón, Bladé, Joan, Prósper, Felipe, Mateo, Gemma, Esseltine, Dixie-Lee, van de Velde, Helgi, San Miguel Izquierdo, Jesús Fernando

مصطلحات موضوعية: Mieloma múltiple, Disease-Free Survival, Immunophenotyping, Aged, Boronic Acids, Humans, Pyrazines, Melphalan, Antineoplastic Combined Chemotherapy Protocols, Antineoplastic Agents, Multiple Myeloma, Maximum Tolerated Dose, Cohort Studies, Prednisone, protocolos de quimioterapia antineoplásica combinada, humanos, anciano, supervivencia sin enfermedad, prednisona, inmunofenotipificación, ácidos borónicos, dosis máxima tolerada, estudios de cohortes, antineoplásicos, piracinas, melfalán

الوصف: [EN]Standard first-line treatment for elderly multiple myeloma (MM) patients ineligible for stem cell transplantation is melphalan plus prednisone (MP). However, complete responses (CRs) are rare. Bortezomib is active in patients with relapsed MM, including elderly patients. This phase 1/2 trial in 60 untreated MM patients aged at least 65 years (half older than 75 years) was designed to determine dosing, safety, and efficacy of bortezomib plus MP (VMP). VMP response rate was 89%, including 32% immunofixation-negative CRs, of whom half of the IF- CR patients analyzed achieved immunophenotypic remission (no detectable plasma cells at 10(-4) to 10(-5) sensitivity). VMP appeared to overcome the poor prognosis conferred by retinoblastoma gene deletion and IgH translocations. Results compare favorably with our historical control data for MP--notably, response rate (89% versus 42%), event-free survival at 16 months (83% versus 51%), and survival at 16 months (90% versus 62%). Side effects were predictable and manageable; principal toxicities were hematologic, gastrointestinal, and peripheral neuropathy and were more evident during early cycles and in patients aged 75 years or more. In conclusion, in elderly patients ineligible for transplantation, the combination of bortezomib plus MP appears significantly superior to MP, producing very high CR rates, including immunophenotypic CRs, even in patients with poor prognostic features.

العلاقة: https://doi.org/10.1182/blood-2006-04-019778Test; Mateos, M. V., Hernández, J. M., Hernández, M. T., Gutiérrez, N. C., Palomera, L., Fuertes, M., . & Miguel, J. F. S. (2006). Bortezomib plus melphalan and prednisone in elderly untreated patients with multiple myeloma: results of a multicenter phase 1/2 study. Blood, 108(7), 2165-2172. https://doi.org/10.1182/blood-2006-04-019778Test; http://hdl.handle.net/10366/154234Test

الإتاحة: https://doi.org/10.1182/blood-2006-04-019778Test
http://hdl.handle.net/10366/154234Test

المؤلفون: Paiva, Bruno, Mateos, María Victoria, Sanchez-Abarca, Luis Ignacio, Puig, Noemi, Vidriales, María-Belén, López-Corral, Lucía, Corchete, Luis A, Hernandez, Miguel T, Bargay, Joan, de Arriba, Felipe, de la Rubia, Javier, Teruel, Ana-Isabel, Giraldo, Pilar, Rosiñol, Laura, Prosper, Felipe, Oriol, Albert, Hernández, José, Esteves, Graça, Lahuerta, Juan José, Bladé, Joan, Perez-Simon, Jose Antonio, San Miguel, Jesús F, Spanish Myeloma Group / Program Study and Treatment of Hematological Malignancies cooperative study groups

المساهمون: Instituto de Salud Carlos III, Asociación Española Contra el Cáncer, European Research Council, Red Temática de Investigación Cooperativa en Cáncer (España)

المصدر: Digital.CSIC. Repositorio Institucional del CSIC
instname
Blood
r-IIS La Fe. Repositorio Institucional de Producción Científica del Instituto de Investigación Sanitaria La Fe
Dadun. Depósito Académico Digital de la Universidad de Navarra

مصطلحات موضوعية: Adult, Male, medicine.medical_treatment, T-Lymphocytes, Immunology, Biochemistry, Dexamethasone, Immunophenotyping, Maintenance Chemotherapy, 03 medical and health sciences, 0302 clinical medicine, Immune system, Aldesleukin, Risk Factors, hemic and lymphatic diseases, Biomarkers, Tumor, Medicine, Humans, IL-2 receptor, Longitudinal Studies, Lenalidomide, Multiple myeloma, Aged, Cell Proliferation, Demography, Aged, 80 and over, business.industry, Cell Biology, Hematology, Immunotherapy, Induction Chemotherapy, Middle Aged, medicine.disease, Thalidomide, Immunosurveillance, Killer Cells, Natural, body regions, 030220 oncology & carcinogenesis, Female, Ciencias de la Salud::Hematología [Materias Investigacion], business, Multiple Myeloma, CD8, 030215 immunology, medicine.drug

الوصف: On behalf of the Grupo Español de Mieloma/Programa de Estudio y Tratamiento de las Hemopatías Malignas cooperative study groups.
There is significant interest in immunotherapy for the treatment of high-risk smoldering multiple myeloma (SMM), but no available data on the immune status of this particular disease stage. Such information is important to understand the interplay between immunosurveillance and disease transformation, but also to define whether patients with high-risk SMM might benefit from immunotherapy. Here, we have characterized T lymphocytes (including CD4, CD8, T-cell receptor γδ, and regulatory T cells), natural killer (NK) cells, and dendritic cells from 31 high-risk SMM patients included in the treatment arm of the QUIREDEX trial, and with longitudinal peripheral blood samples at baseline and after 3 and 9 cycles of lenalidomide plus low-dose dexamethasone (LenDex). High-risk SMM patients showed at baseline decreased expression of activation-(CD25/CD28/CD54), type 1 T helper-(CD195/interferon-γ/tumor necrosis factor-α/interleukin-2), and proliferation-related markers (CD119/CD120b) as compared with age-matched healthy individuals. However, LenDex was able to restore the normal expression levels for those markers and induced a marked shift in T-lymphocyte and NK-cell phenotype. Accordingly, high-risk SMM patients treated with LenDex showed higher numbers of functionally active T lymphocytes. Together, our results indicate that high-risk SMM patients have an impaired immune system that could be reactivated by the immunomodulatory effects of lenalidomide, even when combined with low-dose dexamethasone, and support the value of therapeutic immunomodulation to delay the progression to multiple myeloma.
This study was supported by the Cooperative Research Thematic Network grants RD12/0036/0058 and RD12/0043/0012 of the Red de Cancer (Cancer Network of Excellence); Instituto de Salud Carlos III, Spain, Instituto de Salud Carlos III/Subdirección General de Investigación Sanitaria (FIS: PI060339; 06/1354; 02/0905; 01/0089/01-02; PS09/01897/01370; G03/136; and Sara Borrell: CD13/00340); Asociación Española Contra el Cáncer (GCB120981SAN), Spain; and a European Research Council 2015 Starting Grant (B.P.).

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a00af9d674b2dda137189561ec4bbb03Test
https://hdl.handle.net/10171/52183Test

المؤلفون: Cuker, Adam, Cataland, Spero R, Coppo, Paul, de la Rubia, Javier, Friedman, Kenneth D, George, James N, Knoebl, Paul N, Kremer Hovinga, Johanna A., Lämmle, Bernhard, Matsumoto, Masanori, Pavenski, Katerina, Peyvandi, Flora, Sakai, Kazuya, Sarode, Ravi, Thomas, Mari R, Tomiyama, Yoshiaki, Veyradier, Agnès, Westwood, John-Paul, Scully, Marie

مصطلحات موضوعية: hemic and lymphatic diseases, 610 Medicine & health, 3. Good health

الوصف: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a potentially fatal thrombotic microangiopathy caused by autoantibody-mediated severe deficiency of ADAMTS13. Standardized definitions of response, exacerbation, remission, and relapse were initially proposed in 2003 and modified by the International Working Group for TTP in 2017. These definitions, which have been widely used in clinical practice and research, are based primarily on the platelet count and are benchmarked against the timing of discontinuation of therapeutic plasma exchange (TPE). They do not incorporate ADAMTS13 activity or the temporizing effects on the platelet count of caplacizumab, a novel anti-von Willebrand factor (VWF) nanobody. In light of these limitations, the IWG aimed to develop revised consensus outcome definitions that incorporate ADAMTS13 activity and the effects of anti-VWF therapy, by using an estimate-talk-estimate approach. The updated definitions distinguish clinical remission and clinical relapse (defined primarily by platelet count) from ADAMTS13 remission and ADAMTS13 relapse (defined by ADAMTS13 activity). The revised definitions of exacerbation and remission are benchmarked against not only the timing of discontinuation of TPE but also that of anti-VWF therapy. Retrospective validation of the revised definitions is described, although they have yet to be prospectively validated. Clinical implications of the updated outcome definitions are also discussed and an example of their application to clinical practice is provided to highlight their clinical relevance.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::69e25d93296675de875207db037de0fbTest

المؤلفون: Facon, Thierry¹ thierry.facon@chru-lille.fr, Dimopoulos, Meletios A.², Dispenzieri, Angela³, Catalano, John V.⁴, Belch, Andrew⁵, Cavo, Michele⁶, Pinto, Antonello⁷, Weisel, Katja⁸, Ludwig, Heinz⁹, Bahlis, Nizar J.¹⁰, Banos, Anne¹¹, Tiab, Mourad¹², Delforge, Michel¹³, Cavenagh, Jamie D.¹⁴, Geraldes, Catarina¹⁵, Je-Jung Lee¹⁶, Chen, Christine¹⁷, Oriol, Albert¹⁸, De La Rubia, Javier¹⁹, White, Darrell²⁰

المصدر: Blood. 1/18/2018, Vol. 131 Issue 3, p301-310. 10p.

مصطلحات موضوعية: *MULTIPLE myeloma treatment, *B cell lymphoma, *MONOCLONAL gammopathies, *LYMPHOMAS, *THERAPEUTICS, *PARAPROTEINEMIA

مستخلص: This FIRST trial final analysis examined survival outcomes in patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM) treated with lenalidomide and low-dose dexamethasone until disease progression (Rd continuous), Rd for 72 weeks (18 cycles; Rd18), or melphalan, prednisone, and thalidomide (MPT; 72 weeks). The primary endpoint was progression-free survival (PFS; primary comparison: Rd continuous vs MPT). Overall survival (OS) was a key secondary endpoint (final analysis prespecified ≥60 months' follow-up). Patients were randomized to Rd continuous (n = 535), Rd18 (n = 541), or MPT (n = 547). At a median follow-up of 67 months, PFS was significantly longer with Rd continuous vs MPT (hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.59-0.79; P < .00001) and was similarly extended vs Rd18. Median OS was 10 months longer with Rd continuous vs MPT (59.1 vs 49.1 months; HR, 0.78; 95% CI, 0.67-0.92; P = .0023), and similar with Rd18 (62.3 months). In patients achieving complete or very good partial responses, Rd continuous had an ≈30-month longer median time to next treatment vs Rd18 (69.5 vs 39.9 months). Over half of all patients who received second-line treatment were given a bortezomib-based therapy. Second-line outcomes were improved in patients receiving bortezomib after Rd continuous and Rd18 vs after MPT. No new safety concerns, including risk for secondary malignancies, were observed. Treatment with Rd continuous significantly improved survival outcomes vs MPT, supporting Rd continuous as a standard of care for patients with transplant-ineligible NDMM. [ABSTRACT FROM AUTHOR]

المؤلفون: Jakubowiak, Andrzej¹ ajakubowiak@medicine.bsd.uchicago.edu, Offidani, Massimo², Pégourie, Brigitte³, De La Rubia, Javier⁴, Garderet, Laurent⁵, Laribi, Kamel⁶, Bosi, Alberto⁷, Marasca, Roberto⁸, Laubach, Jacob⁹, Mohrbacher, Ann¹⁰, Carella, Angelo Michele¹¹, Singhal, Anil K.¹², Tsao, L. Claire¹², Lynch, Mark¹³, Bleickardt, Eric¹³, Ying-Ming Jou¹⁴, Robbins, Michael¹⁵, Palumbo, Antonio¹⁶

المصدر: Blood. 6/9/2016, Vol. 127 Issue 23, p2833-2840. 8p.

مصطلحات موضوعية: *RANDOMIZED controlled trials, *MULTIPLE myeloma, *DISEASE progression, *ALLELES, *IMMUNOLOGICAL adjuvants, *PATIENTS

مستخلص: In this proof-of-concept, open-label, phase 2 study, patients with relapsed/refractory multiple myeloma (RRMM) received elotuzumab with bortezomib and dexamethasone (EBd) or bortezomib and dexamethasone (Bd) until disease progression/unacceptable toxicity. Primary endpoint was progression-free survival (PFS); secondary/exploratory endpoints included overall response rate (ORR) and overall survival (OS). Two-sided 0.30 significance level was specified (80% power, 103 events) to detect hazard ratio (HR) of 0.69. Efficacy and safety analyses were performed on all randomized patients and all treated patients, respectively. Of 152 randomized patients (77 EBd, 75 Bd), 150 were treated (75 EBd, 75 Bd).PFSwasgreater withEBdvsBd(HR, 0.72;70%confidence interval [CI], 0.59-0.88; stratified log-rank P 5 .09); median PFS was longer with EBd (9.7 months) vs Bd (6.9 months). In an updated analysis, EBd-treated patients homozygous for the high-affinity FcgRIIIa allele had median PFS of 22.3 months vs 9.8 months in EBd-treated patients homozygous for the low-affinity allele. ORR was 66% (EBd) vs 63% (Bd). Very good partial response or better occurred in 36% of patients (EBd) vs 27% (Bd). Early OS results, based on 40 deaths, revealed anHRof 0.61 (70% CI, 0.43-0.85). To date, 60 deaths have occurred (28 EBd, 32 Bd). No additional clinically significant adverse events occurred with EBd vs Bd. Grade 1/2 infusion reaction rate was low (5% EBd) and mitigated with premedication. In patients with RRMM, elotuzumab, an immunostimulatory antibody, appears to provide clinical benefit without added clinically significant toxicity when combined with Bd vs Bd alone. [ABSTRACT FROM AUTHOR]