72 results on '"González‐Calle, V."'
Search Results
2. ESMO-Magnitude of Clinical Benefit Scale for haematological malignancies (ESMO-MCBS:H) version 1.0
- Author
-
Kiesewetter, B, Dafni, U, de Vries, EGE, Barriuso, J, Curigliano, G, González-Calle, V, Galotti, M, Gyawali, B, Huntly, BJP, Jäger, U, Latino, NJ, Malcovati, L, Oosting, SF, Ossenkoppele, G, Piccart, M, Raderer, M, Scarfò, L, Trapani, D, Zielinski, CC, Wester, R, Zygoura, P, Macintyre, E, Cherny, NI, ESMO-MCBS Working Group and Extended Working Group, Huntly, Brian [0000-0003-0312-161X], and Apollo - University of Cambridge Repository
- Subjects
clinical trials ,quality of life ,clinical benefit ,ESMO-MCBS ,haematological malignancies ,value frameworks - Abstract
BACKGROUND: The European Society for Medical Oncology (ESMO)-Magnitude of Clinical Benefit Scale (MCBS) has been accepted as a robust tool to evaluate the magnitude of clinical benefit reported in trials for oncological therapies. However, the ESMO-MCBS hitherto has only been validated for solid tumours. With the rapid development of novel therapies for haematological malignancies, we aimed to develop an ESMO-MCBS version that is specifically designed and validated for haematological malignancies. METHODS: ESMO and the European Hematology Association (EHA) initiated a collaboration to develop a version for haematological malignancies (ESMO-MCBS:H). The process incorporated five landmarks: field testing of the ESMO-MCBS version 1.1 (v1.1) to identify shortcomings specific to haematological diseases, drafting of the ESMO-MCBS:H forms, peer review and revision of the draft based on re-scoring (resulting in a second draft), assessment of reasonableness of the scores generated, final review and approval by ESMO and EHA including executive boards. RESULTS: Based on the field testing results of 80 haematological trials and extensive review for feasibility and reasonableness, five amendments to ESMO-MCBS were incorporated in the ESMO-MCBS:H addressing the identified shortcomings. These concerned mainly clinical trial endpoints that differ in haematology versus solid oncology and the very indolent nature of nevertheless incurable diseases such as follicular lymphoma, which hampers presentation of mature data. In addition, general changes incorporated in the draft version of the ESMO-MCBS v2 were included, and specific forms for haematological malignancies generated. Here we present the final approved forms of the ESMO-MCBS:H, including instructions. CONCLUSION: The haematology-specific version ESMO-MCBS:H allows now full applicability of the scale for evaluating the magnitude of clinical benefit derived from clinical studies in haematological malignancies.
- Published
- 2023
- Full Text
- View/download PDF
3. Bence Jones proteinuria in smoldering multiple myeloma as a predictor marker of progression to symptomatic multiple myeloma
- Author
-
González-Calle, V, Dávila, J, Escalante, F, de Coca, A G, Aguilera, C, López, R, Bárez, A, Alonso, J M, Hernández, R, Hernández, J M, de la Fuente, P, Puig, N, Ocio, E M, Gutiérrez, N C, García-Sanz, R, and Mateos, M V
- Published
- 2016
- Full Text
- View/download PDF
4. P862: SERUM MASS SPECTROMETRY TO ANALYZE DISEASE RESPONSE IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA RECEIVING ARI0002H, AN ACADEMIC BCMA-DIRECTED CAR T-CELL THERAPY
- Author
-
Ortiz De Landazuri, I., primary, Oliver-Caldés, A., additional, Español-Rego, M., additional, Contreras, M. T., additional, Zabaleta, A., additional, Agulló, C., additional, Puig, N., additional, Cabañas, V., additional, González-Calle, V., additional, Jiménez, R., additional, Inogés, S., additional, Rodríguez-Otero, P., additional, Martin-Antonio, B., additional, Reguera, J. L., additional, López-Diaz de Cerio, A., additional, Benítez-Ribas, D., additional, Rodríguez-Lobato, L. G., additional, González, E. A., additional, Rosiñol, L., additional, Yagüe, J., additional, Moraleda, J. M., additional, Urbano-Ispizua, Á., additional, Mateos, M. V., additional, Juan, M., additional, Paiva, B., additional, Pascal, M., additional, and Fernández de Larrea, C., additional
- Published
- 2022
- Full Text
- View/download PDF
5. S103: EFFICACY AND SAFETY OF ARI0002H, AN ACADEMIC BCMA-DIRECTED CAR-T CELL THERAPY WITH FRACTIONATED INITIAL THERAPY AND BOOSTER DOSE IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA
- Author
-
Fernandez De Larrea, C., primary, González-Calle, V., additional, Oliver-Caldés, A., additional, Cabañas, V., additional, Rodríguez-Otero, P., additional, Español-Rego, M., additional, Reguera, J. L., additional, López-Corral, L., additional, Martin-Antonio, B., additional, Paiva, B., additional, Inogés, S., additional, Rosiñol, L., additional, López-Díaz de Cerio, A., additional, Tovar, N., additional, López-Parra, M., additional, Rodríguez-Lobato, L. G., additional, Sánchez-Salinas, A., additional, Varea, S., additional, Ortiz-Maldonado, V., additional, Pérez Simón, J. A., additional, Prósper, F., additional, Juan, M., additional, Moraleda, J. M., additional, Mateos, M. V., additional, Pascal, M., additional, and Urbano-Ispizua, A., additional
- Published
- 2022
- Full Text
- View/download PDF
6. Dexamethasone as a partner of isatuximab
- Author
-
Mateos, M. V., primary and González-Calle, V., additional
- Published
- 2021
- Full Text
- View/download PDF
7. Pembrolizumab as Consolidation Strategy in Patients with Multiple Myeloma: Results of the GEM-Pembresid Clinical Trial
- Author
-
Puig, N., Corchete Sánchez, Luis Antonio, Pérez-Morán, J. J., Dávila, J., Paíno, T., de la Rubia, J., Oriol, Albert, Martín-Sánchez, J., de Arriba, F., Bladé, J., Blanchard, M. J., González-Calle, V., Garcia-Sanz, R., Paiva, Bruno, Lahuerta, J. J., San-Miguel, J. F., Mateos, M. V., Ocio, E. M., Universitat Autònoma de Barcelona, and Universidad de Cantabria
- Subjects
0301 basic medicine ,Oncology ,Melphalan ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Pembrolizumab ,lcsh:RC254-282 ,Article ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Adverse effect ,Multiple myeloma ,Pneumonitis ,business.industry ,Late effect ,Immunotherapy ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Discontinuation ,030104 developmental biology ,myeloma ,030220 oncology & carcinogenesis ,pembrolizumab ,immunotherapy ,medicine.symptom ,business ,consolidation ,medicine.drug - Abstract
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.
- Published
- 2020
8. International Myeloma Working Group risk stratification model for smoldering multiple myeloma (SMM)
- Author
-
Mateos, M.-V. Kumar, S. Dimopoulos, M.A. González-Calle, V. Kastritis, E. Hajek, R. De Larrea, C.F. Morgan, G.J. Merlini, G. Goldschmidt, H. Geraldes, C. Gozzetti, A. Kyriakou, C. Garderet, L. Hansson, M. Zamagni, E. Fantl, D. Leleu, X. Kim, B.-S. Esteves, G. Ludwig, H. Usmani, S. Min, C.-K. Qi, M. Ukropec, J. Weiss, B.M. Rajkumar, S.V. Durie, B.G.M. San-Miguel, J.
- Abstract
Smoldering multiple myeloma (SMM) is an asymptomatic precursor state of multiple myeloma (MM). Recently, MM was redefined to include biomarkers predicting a high risk of progression from SMM, thus necessitating a redefinition of SMM and its risk stratification. We assembled a large cohort of SMM patients meeting the revised IMWG criteria to develop a new risk stratification system. We included 1996 patients, and using stepwise selection and multivariable analysis, we identified three independent factors predicting progression risk at 2 years: serum M-protein >2 g/dL (HR: 2.1), involved to uninvolved free light-chain ratio >20 (HR: 2.7), and marrow plasma cell infiltration >20% (HR: 2.4). This translates into 3 categories with increasing 2-year progression risk: 6% for low risk (38%; no risk factors, HR: 1); 18% for intermediate risk (33%; 1 factor; HR: 3.0), and 44% for high risk (29%; 2–3 factors). Addition of cytogenetic abnormalities (t(4;14), t(14;16), +1q, and/or del13q) allowed separation into 4 groups (low risk with 0, low intermediate risk with 1, intermediate risk with 2, and high risk with ≥3 risk factors) with 6, 23, 46, and 63% risk of progression in 2 years, respectively. The 2/20/20 risk stratification model can be easily implemented to identify high-risk SMM for clinical research and routine practice and will be widely applicable. © 2020, The Author(s).
- Published
- 2020
9. EHA evaluation of the ESMO-Magnitude of Clinical Benefit Scale version 1.1 (ESMO-MCBS v1.1) for haematological malignancies
- Author
-
Kiesewetter, B. Cherny, N.I. Boissel, N. Cerisoli, F. Dafni, U. De Vries, E.G.E. Ghia, P. Gökbuget, N. González-Calle, V. Huntly, B. Jäger, U. Latino, N.J. Douillard, J.-Y. Malcovati, L. Mateos, M.-V. Ossenkoppele, G.J. Porkka, K. Raderer, M. Ribera, J.-M. Scarfò, L. Wester, R. Zygoura, P. Sonneveld, P.
- Subjects
health care economics and organizations - Abstract
Objective Value frameworks in oncology have not been validated for the assessment of treatments in haematological malignancies, but to avoid overlaps and duplications it appears reasonable to build up experience on existing value frameworks, such as the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS). Methods Here we present the results of the first feasibility testing of the ESMO-MCBS v1.1 for haematological malignancies based on the grading of 80 contemporary studies for acute leukaemia, chronic leukaemia, lymphoma, myeloma and myelodysplastic syndromes. The aims were (1) to evaluate the scorability of data, (2) to evaluate the reasonableness of the generated grades for clinical benefit using the current version and (3) to identify shortcomings in the ESMO-MCBS v1.1 that require amendments to improve the efficacy and validity of the scale in grading new treatments in the management of haematological malignancies. Results In general, the ESMO-MCBS v1.1 was found to be widely applicable to studies in haematological malignancies, generating scores that were judged as reasonable by European Hematology Association (EHA) experts. A small number of studies could either not be graded or were not appropriately graded. The reasons, related to the differences between haematological and solid tumour malignancies, are identified and described. Conclusions Based on the findings of this study, ESMO and EHA are committed to develop a version of the ESMO-MCBS that is validated for haematological malignancies. This development process will incorporate all of the usual stringencies for accountability of reasonableness that have characterised the development of the ESMO-MCBS including field testing, statistical modelling, evaluation for reasonableness and openness to appeal and revision. Applying such a scale will support future public policy decision-making regarding the value of new treatments for haematological malignancies and will provide insights that could be helpful in the design of future clinical trials. © Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology.
- Published
- 2020
10. PS1398 RECOVERY OF POLICLONAL IMMUNOGLOBULINS AS A PREDICTOR FACTOR OF INCREASED PROGRESSION-FREE SURVIVAL AND OVERALL SURVIVAL IN PATIENTS WITH MULTIPLE MYELOMA INELIGIBLE FOR ASCT
- Author
-
Dávila, J., primary, González-Calle, V., additional, Puig, N., additional, Bárez, A., additional, Escalante, F., additional, López, R., additional, Alonso, J.M., additional, Aguilar, C., additional, García-Mateo, A., additional, Contreras, T., additional, Labrador, J., additional, Aguilera, C., additional, de Coca, A. García, additional, Hernández, R., additional, Mateos, M.V., additional, and Ocio, E.M., additional
- Published
- 2019
- Full Text
- View/download PDF
11. PS1008 A NEW NEXT-GENERATION SEQUENCING STRATEGY FOR THE SIMULTANEOUS DETECTION OF GENE MUTATIONS AND COPY NUMBER VARIATIONS IN MYELOID MALIGNANCIES
- Author
-
Prieto-Conde, M.I., primary, Vázquez, I., additional, Fernández-Mercado, M., additional, Gutiérrez, N.C., additional, González-Martínez, T., additional, Larrayoz, M.J., additional, Sarasquete, M.E., additional, Alcoceba, M., additional, González-Calle, V., additional, González-Díaz, M., additional, García-Sanz, R., additional, Calasanz, M.J., additional, and Chillón, M.C., additional
- Published
- 2019
- Full Text
- View/download PDF
12. Serum mass spectrometry for treatment monitoring in patients with multiple myeloma receiving ARI0002h CAR T-cells.
- Author
-
Ortiz de Landazuri I, Oliver-Caldés A, Español-Rego M, Agulló C, Contreras MT, Zabaleta A, Puig N, Cabañas V, González-Calle V, Zugasti I, Inogés S, Rodríguez Otero P, Martin-Antonio B, Reguera JL, López-Diaz de Cerio A, Aróstegui JI, Uribe-Herranz M, Benítez-Ribas D, Rodríguez-Lobato LG, González EA, Tovar N, Charry P, Navarro S, Rosiñol L, Tréboles K, Mora G, Yagüe J, Moraleda JM, Urbano-Ispizua Á, Mateos MV, Pascal M, Paiva B, Juan M, and Fernández de Larrea C
- Subjects
- Humans, Male, Female, Middle Aged, Aged, Receptors, Chimeric Antigen, Myeloma Proteins analysis, Adult, Antibodies, Monoclonal, Humanized therapeutic use, B-Cell Maturation Antigen, Multiple Myeloma therapy, Multiple Myeloma blood, Immunotherapy, Adoptive methods, Mass Spectrometry methods
- Abstract
Chimeric antigen receptor (CAR) T-cell therapies have increased the patients with relapsed/refractory multiple myeloma (RRMM) in whom standard electrophoretic techniques fail to detect the M-protein. Quantitative immunoprecipitation mass spectrometry (QIP-MS) can accurately measure serum M-protein with high sensitivity, and identify interferences caused by therapeutic monoclonal antibodies. Here, we investigate the outcome of QIP-MS in 33 patients treated with the academic BCMA-directed CAR T-cell ARI0002h (Cesnicabtagene Autoleucel). QIP-MS offered more detailed insights than serum immunofixation (sIFE), identifying glycosylated M-proteins and minor additional peaks. Moreover, the potential interferences owing to daratumumab or tocilizumab treatments were successfully detected. When analysing different assay platforms during patient's monitoring after ARI0002h administration, we observed that QIP-MS showed a high global concordance (78.8%) with sIFE, whereas it was only moderate (55.6%) with bone marrow (BM)-based next-generation flow cytometry (NGF). Furthermore, QIP-MS consistently demonstrated the lowest negativity rate across the different timepoints (27.3% vs. 60.0% in months 1 and 12, respectively). Patients with QIP-MS(+)/BM-based NGF(-) showed a non-significant shorter median progression free survival than those with QIP-MS(-)/BM-based NGF(-). In summary, we show the first experience to our knowledge demonstrating that QIP-MS could be particularly useful as a non-invasive technique when evaluating response after CAR T-cell treatment in MM., (© 2024 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)
- Published
- 2024
- Full Text
- View/download PDF
13. Curative Strategy for High-Risk Smoldering Myeloma: Carfilzomib, Lenalidomide, and Dexamethasone (KRd) Followed by Transplant, KRd Consolidation, and Rd Maintenance.
- Author
-
Mateos MV, Martínez-López J, Rodriguez Otero P, González-Calle V, Gonzalez MS, Oriol A, Gutiérrez NC, Ríos-Tamayo R, Rosiñol L, Alvarez Rivas MA, Bargay J, Gonzalez-Rodriguez AP, Alegre A, Escalante F, Iñigo Rodríguez MB, De La Rubia J, Teruel AI, de Arriba F, Palomera L, Hernández MT, Lopez Jiménez J, Reinoso-Segura M, García Mateo A, Ocio EM, Paiva B, Puig N, Cedena MT, Bladé J, Lahuerta JJ, and San-Miguel JF
- Subjects
- Humans, Male, Female, Middle Aged, Aged, Adult, Hematopoietic Stem Cell Transplantation methods, Transplantation, Autologous, Melphalan administration & dosage, Melphalan therapeutic use, Consolidation Chemotherapy, Maintenance Chemotherapy, Multiple Myeloma drug therapy, Multiple Myeloma therapy, Disease Progression, Lenalidomide administration & dosage, Lenalidomide therapeutic use, Lenalidomide adverse effects, Dexamethasone administration & dosage, Dexamethasone therapeutic use, Oligopeptides therapeutic use, Oligopeptides administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Antineoplastic Combined Chemotherapy Protocols adverse effects, Smoldering Multiple Myeloma drug therapy
- Abstract
Purpose: Early treatment of high-risk smoldering myeloma has been shown to delay progression to multiple myeloma (MM). We conducted this trial with curative intention using a treatment approach employed for newly diagnosed patients with MM., Methods: Patients with high-risk smoldering myeloma (>50% progression risk at 2 years) and transplant candidates were included and received induction therapy with carfilzomib, lenalidomide, and dexamethasone (KRd), six cycles, followed by high-dose melphalan (200 mg/m
2 ) autologous stem-cell transplantation (HDM-ASCT), two KRd consolidation cycles, and Rd maintenance for 2 years. The primary end point was undetectable measurable residual disease (uMRD) rate by next-generation flow after ASCT. Sustained uMRD 4 years after ASCT was the secondary end point., Results: Between June 2015 and June 2017, 90 patients were included, and 31% met at least one SixtyLightchain MRI (SLiM)-hypercalcemia, renal impairment, anemia, bone disease (CRAB) criterion. After a median follow-up of 70.1 months, 3 months after ASCT, in the intention-to-treat population, 56 (62%) of 90 patients had uMRD, and 4 years later, it was sustained in 29 patients (31%). Five patients progressed to MM, and the 70-month progression rate was 94% (95% CI, 84 to 89). The presence of any SLiM CRAB criteria predicted progression to MM (four of the five patients; hazard ratio, 0.12; 95% CI, 0.14 to 1.13; P = .03). Thirty-six patients showed biochemical progression, and failure to achieve uMRD at the end of treatment predicted it. The 70-month overall survival was 92% (95% CI, 82 to 89). Neutropenia and infections were the most frequent adverse events during treatment, resulting in one treatment-related death. Three second primary malignancies have been reported., Conclusion: Although a longer follow-up is needed, this curative approach is encouraging and more effective than active MM, with 31% of the patients maintaining the uMRD 4 years after HDM-ASCT.- Published
- 2024
- Full Text
- View/download PDF
14. Single-point and kinetics of peripheral residual disease by mass spectrometry to predict outcome in patients with high risk smoldering multiple myeloma included in the GEM-CESAR trial.
- Author
-
Puig N, Agulló C, Contreras T, Pérez JJ, Aires I, Calasanz MJ, García-Sanz R, Castro S, Martínez-López J, Rodríguez-Otero P, González-Calle V, González MS, Oriol A, Gutiérrez NC, Ríos-Tamayo R, Rosiñol L, Álvarez MÁ, Bargay J, González-Rodríguez AP, Alegre A, Escalante F, Iñigo MB, De la Rubia J, Teruel AI, De Arriba F, Palomera L, Hernández MT, López-Jiménez J, Reinoso M, García-Mateo A, Ocio EM, Bladé J, Lahuerta JJ, Cedena MT, Paiva B, Miguel JFS, and Mateos MV
- Abstract
The value of quantitative immunoprecipitation mass spectrometry (QIP-MS) to identify the M-protein is being investigated in patients with monoclonal gammopathies but no data are yet available in high-risk smoldering myeloma (HRsMM). We have therefore investigated QIP-MS to monitor peripheral residual disease (PRD) in 62 HRsMM patients enrolled in the GEM-CESAR trial. After 24 cycles of maintenance, detecting the M-protein by MS or clonal plasma cells by NGF identified cases with a significantly shorter median PFS (mPFS; MS: not reached vs 1,4 years, p=0.001; NGF: not reached vs 2 years, p=0.0002) but reaching CR+sCR did not discriminate patients with different outcome. With NGF as a reference, the combined results of NGF and MS showed a high negative predictive value (NPV) of MS: 81% overall and 73% at treatment completion. When sequential results were considered, sustained negativity by MS or NGF was associated with a very favorable outcome with a mPFS not yet reached vs 1.66 years and 2.18 years in cases never attaining PRD or minimal residual disease (MRD) negativity, respectively. We can thus conclude that 1) the standard response categories of the IMWG do not seem to be useful for treatment monitoring in HRsMM patients, 2) MS could be used as a non-invasive, clinical valuable tool with the capacity of guiding timely bone marrow evaluations (based on its high NPV with NGF as a reference) and 3) similarly to NGF, sequential results of MS are able identify a subgroup of HRsMM patients with long-term disease control. This study was registered at www.clinicaltrials.gov (ClinicalTrials.gov identifier: NCT02415413).
- Published
- 2024
- Full Text
- View/download PDF
15. A research center's experience of T-cell-redirecting therapies in triple-class refractory multiple myeloma.
- Author
-
Puertas B, Fernández-Sánchez A, Alejo E, Rey-Búa B, Martín-López AA, Pérez-López E, López-Parra M, López-Corral L, Gutiérrez-Gutiérrez NC, García-Sanz R, Puig N, González-Calle V, and Mateos MV
- Subjects
- Humans, Male, Female, Middle Aged, Aged, Retrospective Studies, T-Lymphocytes immunology, Antibodies, Bispecific therapeutic use, Adult, Treatment Outcome, Multiple Myeloma therapy, Multiple Myeloma mortality, Multiple Myeloma immunology, Immunotherapy, Adoptive methods, Receptors, Chimeric Antigen
- Abstract
Abstract: The efficacies of chimeric antigen receptor T cells (CAR-Ts) and bispecific monoclonal antibodies (BiAbs) for triple-class refractory (TCR) myeloma have not previously been compared, and clinical data on how to rescue patients after relapse from these immunotherapies are limited. A retrospective study of 73 TCR patients included in trials was conducted: 36 received CAR-Ts and 37 received BiAbs. CAR-Ts produced a higher overall response rate (ORR) than BiAbs (97.1% vs 56.8%, P = .002). After a median of follow-up of 18.7 months, no significant difference in progression-free survival (PFS) was observed between the CAR-T and BiAbs groups (16.6 vs 10.8 months; P = .090), whereas overall survival (OS) was significantly longer in the CAR-T than in the BiAbs group (49.2 vs 22.6 months; P = .021). BiAbs after CAR-Ts yielded a higher ORR and longer PFS2 than did nonredirecting T-cell therapies after CAR-Ts (ORR: 87.5% vs 50.0%; PFS2: 22.9 vs 12.4 months). By contrast, BiAbs after BiAbs resulted in an ORR of 33% and PFS2 of 8.4 months, which was similar to that produced by the nonredirecting T-cell therapies (ORR: 28.6%; PFS2: 8.1 months). Although this is a pooled analysis of different trials with different products and the patient profile is different for CAR-Ts and BiAbs, both were effective therapies for TCR myeloma. However, in our experience, although the PFS was similar with the 2 approaches, CAR-T therapy resulted in better OS, mainly because of the efficacy of BiAbs as rescue therapy. Our results highlight the importance of treatment sequence in real-word experience., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
16. Selinexor, daratumumab, bortezomib and dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma: results of the phase II, nonrandomized, multicenter GEM-SELIBORDARA study.
- Author
-
González-Calle V, Rodríguez-Otero P, Sureda A, De Arriba F, Reinoso M, Ribas P, González-Rodríguez AP, González Y, Oriol A, Martínez-López J, González MS, Hernández MT, Sirvent M, Cedena T, Puig N, Paiva B, Bladé J, Lahuerta JJ, San-Miguel JF, and Mateos MV
- Subjects
- Humans, Male, Female, Aged, Middle Aged, Aged, 80 and over, Adult, Treatment Outcome, Drug Resistance, Neoplasm, Recurrence, Multiple Myeloma drug therapy, Multiple Myeloma mortality, Dexamethasone administration & dosage, Dexamethasone therapeutic use, Triazoles administration & dosage, Triazoles therapeutic use, Triazoles adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Antineoplastic Combined Chemotherapy Protocols adverse effects, Bortezomib administration & dosage, Bortezomib therapeutic use, Hydrazines administration & dosage, Hydrazines therapeutic use, Hydrazines adverse effects, Antibodies, Monoclonal therapeutic use, Antibodies, Monoclonal administration & dosage, Antibodies, Monoclonal adverse effects
- Abstract
The treatment landscape for multiple myeloma has significantly evolved in the last decade. Notwithstanding, a large proportion of patients continue to relapse and novel combinations continue to be needed. In this phase II study, selinexor, a first-in-class inhibitor of exportin-1 was evaluated in combination with standard daratumumab-bortezomib-dexamethasone (DVd), for the treatment of relapsed and refractory multiple myeloma (RRMM). The aim of the trial was to assess the efficacy and safety of the combination of selinexor with DVd (S-DVd). A total of 57 patients were enrolled in the two parts of the study. Part 1 enrolled a heavily pretreated population with at least three prior lines (PL) of therapy and part 2 enrolled an early relapse population with at least one PL of therapy. The primary endpoint was complete response (CR) rate in part 2 and overall response rate (ORR) in part 1. In the latter, 24 patients were treated with a median of three PL. Overall response rate (ORR) was 50% with two CR. Median progression- free survival (PFS) was 7 months. In part 2, 33 patients were enrolled, with a median of one PL. ORR was 82% and CR or better was 33%. Median PFS was 24 months. In lenalidomide-refractory patients, a median PFS of 22.1 months was observed. Thrombocytopenia was the most common hematological adverse event (69%; grade 3-4: 34%) and nausea, the most frequent non-hematological adverse event (38%; grade 3-4: 6%). Sixty-two percent of the patients required dose modifications. In summary, although the primary endpoint of the study was not met, the combination of S-DVd showed encouraging clinical efficacy with a generally manageable safety profile representing a potential option for the treatment of RRMM patients.
- Published
- 2024
- Full Text
- View/download PDF
17. Mass Spectrometry as Alternative Method to Identify and Monitor Non-Secretory Progressive Disease in Patients with Multiple Myeloma.
- Author
-
Agulló C, Puig N, Contreras T, Castro S, Puertas B, González-Calle V, Rey-Búa B, and Mateos MV
- Abstract
Introduction: After receiving different lines of treatment, multiple myeloma patients tend to present with less secretory and more frequent extramedullary disease. These features make treatment monitoring and follow-up very complex since they have to be based on the use of imaging methods and/or bone marrow aspirations or biopsies., Objective: To present the case of a patient with myeloma progressing with non-secretory bone disease and to discuss the potential impact of mass spectrometry as a new highly sensitive method able to identify the monoclonal protein (MP) in the serum of these types of patients., Materials and Methods: Informed consent was signed by the patient prior to receiving each line of treatment. The clinical information and images were obtained from anonymized electronic files. The mass spectrometry was performed with the Immunoglobulin Isotypes (GAM) assay for the mass spectrometry EXENT
® Analyser Technology from Binding Site, part of Thermofisher., Results: A 73-year-old male with IgG kappa multiple myeloma progressing with a new lytic lesion after receiving 14 cycles of Talquetamab as a third line of therapy who, due to the non-secretory nature of the disease at this point, could not be enrolled in a clinical trial, thus limiting his therapeutic options. The mass spectrometry was able to identify and quantify the presence of the patient's MP when the serum protein electrophoresis and immunofixation were still negative and therefore could have been used to confirm the progression, to permit the inclusion of the patient in a clinical trial and to further monitor the disease response., Conclusions: The higher sensitivity of the mass spectrometry methods to detect the MP in patients with myeloma and other monoclonal gammopathies translates into better identification of the disease progression, permits the inclusion of more patients in clinical trials and facilitates treatment monitoring.- Published
- 2024
- Full Text
- View/download PDF
18. Biomarkers of Efficacy and Safety of the Academic BCMA-CART ARI0002h for the Treatment of Refractory Multiple Myeloma.
- Author
-
Oliver-Caldes A, Español-Rego M, Zabaleta A, González-Calle V, Navarro-Velázquez S, Inogés S, de Cerio AL, Cabañas V, López-Muñoz N, Rodríguez-Otero P, Reguera JL, Moreno DF, Martínez-Cibrian N, López-Corral L, Pérez-Amill L, Martin-Antonio B, Rosiñol L, Cid J, Tovar N, Sáez-Peñataro J, López-Parra M, Olesti E, Guillén E, Varea S, Rodríguez-Lobato LG, Battram AM, González MS, Sánchez-Salinas A, González-Navarro A, Ortiz-Maldonado V, Delgado J, Prósper F, Juan M, Martínez-López J, Moraleda JM, Mateos MV, Urbano-Ispizua Á, Paiva B, Pascal M, and Fernández de Larrea C
- Subjects
- Humans, Male, Female, Middle Aged, Aged, Adult, Biomarkers, Tumor, Receptors, Chimeric Antigen immunology, Treatment Outcome, Multiple Myeloma therapy, Multiple Myeloma immunology, Multiple Myeloma drug therapy, B-Cell Maturation Antigen immunology, B-Cell Maturation Antigen antagonists & inhibitors, Immunotherapy, Adoptive adverse effects, Immunotherapy, Adoptive methods
- Abstract
Purpose: B-cell maturation antigen (BCMA)-chimeric antigen receptor T-cells (CART) improve results obtained with conventional therapy in the treatment of relapsed/refractory multiple myeloma. However, the high demand and expensive costs associated with CART therapy might prove unsustainable for health systems. Academic CARTs could potentially overcome these issues. Moreover, response biomarkers and resistance mechanisms need to be identified and addressed to improve efficacy and patient selection. Here, we present clinical and ancillary results of the 60 patients treated with the academic BCMA-CART, ARI0002h, in the CARTBCMA-HCB-01 trial., Patients and Methods: We collected apheresis, final product, peripheral blood and bone marrow samples before and after infusion. We assessed BCMA, T-cell subsets, CART kinetics and antibodies, B-cell aplasia, cytokines, and measurable residual disease by next-generation flow cytometry, and correlated these to clinical outcomes., Results: At cut-off date March 17, 2023, with a median follow-up of 23.1 months (95% CI, 9.2-37.1), overall response rate in the first 3 months was 95% [95% confidence interval (CI), 89.5-100]; cytokine release syndrome (CRS) was observed in 90% of patients (5% grades ≥3) and grade 1 immune effector cell-associated neurotoxicity syndrome was reported in 2 patients (3%). Median progression-free survival was 15.8 months (95% CI, 11.5-22.4). Surface BCMA was not predictive of response or survival, but soluble BCMA correlated with worse clinical outcomes and CRS severity. Activation marker HLA-DR in the apheresis was associated with longer progression-free survival and increased exhaustion markers correlated with poorer outcomes. ARI0002h kinetics and loss of B-cell aplasia were not predictive of relapse., Conclusions: Despite deep and sustained responses achieved with ARI0002h, we identified several biomarkers that correlate with poor outcomes., (©2024 American Association for Cancer Research.)
- Published
- 2024
- Full Text
- View/download PDF
19. A Simple Frailty Score Predicts Survival and Early Mortality in Systemic AL Amyloidosis.
- Author
-
Ríos-Tamayo R, Lecumberri R, Cibeira MT, González-Calle V, Alonso R, Domingo-González A, Landete E, Encinas C, Iñigo B, Blanchard MJ, Alejo E, Krsnik I, Gómez-Bueno M, Garcia-Pavia P, Segovia-Cubero J, Rosiñol L, Lahuerta JJ, Martínez-López J, and Bladé J
- Abstract
Systemic AL amyloidosis is a challenging disease for which many patients are considered frail in daily clinical practice. However, no study has so far addressed frailty and its impact on the outcome of these patients. We built a simple score to predict mortality based on three frailty-associated variables: age, ECOG performance status (<2 vs. ≥2) and NT-proBNP (<8500 vs. ≥8500 ng/L). Four-hundred and sixteen consecutive newly diagnosed patients diagnosed at ten sites from the Spanish Myeloma Group were eligible for the study. The score was developed in a derivation cohort from a referral center, and it was externally validated in a multicenter cohort. Multivariate analysis showed that the three variables were independent predictors of survival. The score was able to discriminate four groups of patients in terms of overall survival and early mortality in both cohorts. Comorbidity was also analyzed with the Charlson comorbidity index, but it did not reach statistical significance in the model. A nomogram was created to easily estimate the mortality risk of each patient at each time point. This score is a simple, robust, and efficient approach to dynamically assess frailty-dependent mortality both at diagnosis and throughout follow-up. The optimal treatment for frail AL amyloidosis patients remains to be determined but we suggest that the estimation of frailty-associated risk could complement current staging systems, adding value in clinical decision-making in this complex scenario.
- Published
- 2024
- Full Text
- View/download PDF
20. Single-Cell DNA Sequencing and Immunophenotypic Profiling to Track Clonal Evolution in an Acute Myeloid Leukemia Patient.
- Author
-
García-Álvarez M, Yeguas A, Jiménez C, Medina-Herrera A, González-Calle V, Hernández-Ruano M, Maldonado R, Aires I, Casquero C, Sánchez-Villares I, Balanzategui A, Sarasquete ME, Alcoceba M, Vidriales MB, González-Díaz M, García-Sanz R, and Chillón MC
- Abstract
Single-cell DNA sequencing can address the sequence of somatic genetic events during myeloid transformation in relapsed acute myeloid leukemia (AML). We present an NPM1 -mutated AML patient with an initial low ratio of FLT3 -ITD (low-risk ELN-2017), treated with midostaurin combined with standard chemotherapy as front-line treatment, and with salvage therapy plus gilteritinib following allogenic stem cell transplantation after relapse. Simultaneous single-cell DNA sequencing and cell-surface immunophenotyping was used in diagnostic and relapse samples to understand the clinical scenario of this patient and to reconstruct the clonal composition of both tumors. Four independent clones were present before treatment: DNMT3A/DNMT3A/NPM1 (63.9%), DNMT3A/DNMT3A (13.9%), DNMT3A/DNMT3A/NPM1/FLT3 (13.8%), as well as a wild-type clone (8.3%), but only the minor clone with FLT3 -ITD survived and expanded after therapy, being the most represented one (58.6%) at relapse. FLT3 -ITD was subclonal and was found only in the myeloid blast population (CD38/CD117/CD123). Our study shows the usefulness of this approach to reveal the clonal architecture of the leukemia and the identification of small subclones at diagnosis and relapse that may explain how the neoplastic cells can escape from the activity of different treatments in a stepwise process that impedes the disease cure despite different stages of complete remission.
- Published
- 2023
- Full Text
- View/download PDF
21. Assessment of the psychometric properties of the Spanish version of EORTC QLQ-MY20 and evaluation of health-related quality of Life outcomes in patients with relapsed and/or refractory multiple myeloma in the real-world setting in Spain: results from the CharisMMa study.
- Author
-
Dachs LR, Gaisán CM, Bustamante G, López SG, García EG, Persona EP, González-Calle V, Auzmendi MS, Pérez JMA, González Montes Y, Ríos Tamayo R, de Miguel Llorente D, Bernal LP, Mayol AS, Caro CC, Grande M, Fernández-Nistal A, Naves A, and Miguel EMOS
- Subjects
- Female, Humans, Male, Cross-Sectional Studies, Psychometrics, Quality of Life, Reproducibility of Results, Spain epidemiology, Middle Aged, Aged, Multiple Myeloma diagnosis, Multiple Myeloma epidemiology, Multiple Myeloma therapy
- Abstract
We evaluated the psychometric properties of the Spanish version of the European Organization for Research and Treatment of Multiple Myeloma (MM) specific quality-of-life (QoL) questionnaire module (QLQ-MY20) in relapsed/refractory MM (RRMM) patients. This was an observational, cross-sectional, multicenter study using EORTC QLQ-C30 and QLQ-MY20 in RRMM patients (ClinicalTrials.gov ID NCT03188536). We assessed the non-response rate, ceiling/floor effects, internal consistency, test-retest reliability, and validity. The study included 276 patients (53.3% males, mean [SD] age of 67.4 [10.5] years). The EORTC QLQ-MY20 showed a low non-response rate, very low ceiling and floor effects, and good internal consistency. The test-retest reliability assessment revealed good temporary stability, the construct validity analysis stated four main factors similar to the ones of the original version, and the criterion validity assessment showed no differences between groups. In conclusion, the Spanish version of EORTC QLQ-MY20 is a reliable and valid tool for assessing QoL in RRMM patients.
- Published
- 2023
- Full Text
- View/download PDF
22. Randomized phase II study of weekly carfilzomib 70 mg/m 2 and dexamethasone with or without cyclophosphamide in relapsed and/or refractory multiple myeloma patients.
- Author
-
Puertas B, González-Calle V, Sureda A, Moreno MJ, Oriol A, González E, Rosiñol L, López J, Escalante F, Martínez-Lopez J, Carrillo E, Clavero E, Ríos-Tamayo R, Rey-Bua B, González-Rodríguez AP, Dourdil V, De Arriba F, González S, Pérez-de-Oteyza J, Hernández MT, García-Mateo A, Bargay J, Bladé J, Lahuerta JJ, San Miguel JF, Ocio EM, and Mateos MV
- Subjects
- Humans, Aged, Lenalidomide therapeutic use, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols adverse effects, Cyclophosphamide adverse effects, Dexamethasone adverse effects, Multiple Myeloma drug therapy
- Abstract
In this randomized phase II study (GEM-KyCyDex, clinicaltrials gov. Identifier: NCT03336073), the combination of weekly carfilzomib 70 mg/m2, cyclophosphamide and dexamethasone (KCd) was compared to carfilzomib and dexamethasone (Kd) in relapsed/refractory multiple myeloma (RRMM) after 1-3 prior lines (PL). One hundred and ninety-seven patients were included and randomized 1:1 to receive KCd (97 patients) or Kd (100 patients) in 28-day cycles until progressive disease or unacceptable toxicity occurred. Patient median age was 70 years, and the median number of PL was one (range, 1-3). More than 90% of patients had previously been exposed to proteasome inhibitors, approximetely 70% to immunomodulators, and approximetely 50% were refractory to their last line (mainly lenalidomide) in both groups. After a median follow-up of 37 months, median progression-free survival (PFS) was 19.1 and 16.6 months in KCd and Kd, respectively (P=0.577). Of note, in the post hoc analysis of the lenalidomide-refractory population, the addition of cyclophosphamide to Kd resulted in a significant benefit in terms of PFS: 18.4 versus 11.3 months (hazard ratio =1.7, 95% confidence interval: 1.1-2.7; P=0.043). The overall response rate and the percentage of patients who achieved complete response was around 70% and 20% in both groups. The addition of cyclophosphamide to Kd did not result in any safety signal, except for severe infections (7% vs. 2%). In conclusion, the combination of cyclophosphamide with Kd 70 mg/m2 weekly does not improve outcomes as compared with Kd alone in RRMM after 1-3 PL, but a significant benefit in PFS was observed with the triplet combination in the lenalidomide-refractory population. The administration of weekly carfilzomib 70 mg/m2 was safe and convenient, and, overall, the toxicity was manageable in both arms.
- Published
- 2023
- Full Text
- View/download PDF
23. Real-World Health Care Services Utilization Associated With the Management of Patients With Relapsed and Refractory Multiple Myeloma in Spain: The CharisMMa Study.
- Author
-
Ocio EM, Montes-Gaisán C, Bustamante G, Garzón S, González E, Pérez-Persona E, González-Calle V, Sirvent M, Arguiñano JM, González Y, Ríos R, de Miguel D, Grande M, Fernández-Nistal A, Naves A, and Rosiñol L
- Subjects
- Male, Humans, Child, Female, Spain epidemiology, Cross-Sectional Studies, Facilities and Services Utilization, Global Health, Neoplasm Recurrence, Local drug therapy, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Multiple Myeloma epidemiology, Multiple Myeloma therapy, Multiple Myeloma diagnosis
- Abstract
Background: Most patients with multiple myeloma (MM) relapse or become refractory, resulting in high health care costs. However, real-world data regarding the utilization of health care services among the relapsed/refractory MM (RRMM) population are scarce., Methods: Observational, cross-sectional, multicenter study of the utilization of health care services by RRMM patients who had relapsed within the previous 6 months in Spain in a real-world setting. Data were collected from the clinical records and during a single structured interview and included sociodemographic and clinical characteristics at last relapse, the treatment and health care services nature, and were presented using descriptive statistics., Results: The 276 patients enrolled (53.3% males), with a mean [SD] age of 67.4 [10.5] years, had experienced their most recent relapse a median (IQR) of 1.61 (0.74, 3.14) months before entering the study. Patients lived a median (IQR) of 9.0 (3.0, 30.0) km away from the hospital and visited the hospital a median (IQR) of 3.0 (2.0, 5.0) times/month to receive treatment for their most recent relapse. They spent a median (IQR) of 15.84 (5.0, 42.0) euros/month on transportation. Since their most recent relapse, most patients had been admitted to a hospital unit (n = 155, 56.2%), had required ≥1 diagnostic tests (n = 227, 82.2%), and had consulted the hematologist (n = 270, 97.8%) a mean (SD) of 5.5 (5.4) times. In half of the visits, patients were accompanied by an actively working caregiver (n = 112, 54.4%)., Conclusions: RRMM treatments are associated with a high utilization of health care services and pose a significant burden for patients and caregivers., Trial Registration Number: NCT03188536., Competing Interests: Disclosure EMO has received research support from GSK; honoraria from BMS/Celgene, Janssen, Sanofi, GSK, Oncopeptides, Amgen, MSD, and Takeda; and consultancy fees from BMS/Celgene, Janssen, GSK, Pfizer, Amgen, Sanofi, Secura-Bio, Oncopeptides, Karyopharm, and Takeda. EP-P has received fees as consultant from Celgene, Amgen, Takeda, and Janssen; and fees as speaker from Roche, Celgene, Amgen, Janssen, Abbvie, and Jazz Pharmaceutical. MS has received financial support from Celgene, Janssen, and Takeda. JMA has received consultancy fees from BMS, Amgen, Janssen, Abbvie, GSK, and Sanofi; and honoraria from Novartis, Takeda, Janssen, BMS, Roche, Sanofi, Abbvie, GSK, and Amgen. RR has received consultancy fees from Becton-Dickinson, Sanofi, and The Binding Site. LR has received honoraria from Janssen, Celgene, Amgen, and Takeda. MG, AF, and AN are employees of Takeda. CM-G, GB, SG, EG, VG-C, YG, and DM declare no conflicts of interest., (Copyright © 2023. Published by Elsevier Inc.)
- Published
- 2023
- Full Text
- View/download PDF
24. Fractionated initial infusion and booster dose of ARI0002h, a humanised, BCMA-directed CAR T-cell therapy, for patients with relapsed or refractory multiple myeloma (CARTBCMA-HCB-01): a single-arm, multicentre, academic pilot study.
- Author
-
Oliver-Caldés A, González-Calle V, Cabañas V, Español-Rego M, Rodríguez-Otero P, Reguera JL, López-Corral L, Martin-Antonio B, Zabaleta A, Inogés S, Varea S, Rosiñol L, López-Díaz de Cerio A, Tovar N, Jiménez R, López-Parra M, Rodríguez-Lobato LG, Sánchez-Salinas A, Olesti E, Calvo-Orteu M, Delgado J, Pérez-Simón JA, Paiva B, Prósper F, Sáez-Peñataro J, Juan M, Moraleda JM, Mateos MV, Pascal M, Urbano-Ispizua A, and Fernández de Larrea C
- Subjects
- Humans, Male, Female, Middle Aged, Immunotherapy, Adoptive adverse effects, B-Cell Maturation Antigen, Pilot Projects, Cytokines, Multiple Myeloma drug therapy, COVID-19
- Abstract
Background: Chimeric antigen receptor (CAR) T-cell therapy is a promising option for patients with heavily treated multiple myeloma. Point-of-care manufacturing can increase the availability of these treatments worldwide. We aimed to assess the safety and activity of ARI0002h, a BCMA-targeted CAR T-cell therapy developed by academia, in patients with relapsed or refractory multiple myeloma., Methods: CARTBCMA-HCB-01 is a single-arm, multicentre study done in five academic centres in Spain. Eligible patients had relapsed or refractory multiple myeloma and were aged 18-75 years; with an Eastern Cooperative Oncology Group performance status of 0-2; two or more previous lines of therapy including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody; refractoriness to the last line of therapy; and measurable disease according to the International Myeloma Working Group criteria. Patients received an initial fractionated infusion of 3 × 10
6 CAR T cells per kg bodyweight in three aliquots (0·3, 0·9, and 1·8 × 106 CAR-positive cells per kg intravenously on days 0, 3, and 7) and a non-fractionated booster dose of up to 3 × 106 CAR T cells per kg bodyweight, at least 100 days after the first infusion. The primary endpoints were overall response rate 100 days after first infusion and the proportion of patients developing cytokine-release syndrome or neurotoxic events in the first 30 days after receiving treatment. Here, we present an interim analysis of the ongoing trial; enrolment has ended. This study is registered with ClinicalTrials.gov, NCT04309981, and EudraCT, 2019-001472-11., Findings: Between June 2, 2020, and Feb 24, 2021, 44 patients were assessed for eligibility, of whom 35 (80%) were enrolled. 30 (86%) of 35 patients received ARI0002h (median age 61 years [IQR 53-65], 12 [40%] were female, and 18 [60%] were male). At the planned interim analysis (cutoff date Oct 20, 2021), with a median follow-up of 12·1 months (IQR 9·1-13·5), overall response during the first 100 days from infusion was 100%, including 24 (80%) of 30 patients with a very good partial response or better (15 [50%] with complete response, nine [30%] with very good partial response, and six [20%] with partial response). Cytokine-release syndrome was observed in 24 (80%) of 30 patients (all grade 1-2). No cases of neurotoxic events were observed. Persistent grade 3-4 cytopenias were observed in 20 (67%) patients. Infections were reported in 20 (67%) patients. Three patients died: one because of progression, one because of a head injury, and one due to COVID-19., Interpretation: ARI0002h administered in a fractioned manner with a booster dose after 3 months can provide deep and sustained responses in patients with relapsed or refractory multiple myeloma, with a low toxicity, especially in terms of neurological events, and with the possibility of a point-of-care approach., Funding: Instituto de Salud Carlos III (co-funded by the EU), Fundación La Caixa, and Fundació Bosch i Aymerich., Competing Interests: Declaration of interests AO-C declares support for attending meetings from Janssen. VG-C declares receiving honoraria from Janssen, Pfizer, Bristol Myers Squibb (BMS)/Celgene, and GSK; support for attending meetings or travel from Janssen and GSK; and participation on data safety monitoring or advisory board from Janssen. VC declares receiving honoraria from Janssen, BMS, Sanofi, GSK, and Amgen; support for attending meetings or travel from Janssen; and participation on data safety monitoring or advisory board from Janssen, Sanofi, and Amgen. PR-O declares receiving honoraria from consulting activities from BMS, Janssen, Sanofi, Abbvie, Pfizer, Roche, and GSK; honoraria from lectures from BMS, Janssen, Sanofi and GSK; support for attending meetings or travel from Abbvie; and participation on data safety monitoring or advisory board from Janssen. JLR declares receiving consulting fees from Janssen; honoraria from Janssen, Amgen, Sanofi, Kite/Gilead, Novartis, and BMS; support for attending meetings or travel from Kite/Gilead; and participation on data safety monitoring or advisory board from Janssen, BMS, and Novartis. LL-C declares receiving honoraria from Kite/Gilead, Celgene, Janssen, and Novartis; support for attending meetings or travel from Kite/Gilead, Celgene, Janssen, and Novartis; and participation on data safety monitoring or advisory board from Janssen. BM-A declares to be co-inventor in the patent of ARI0002. LR declares honoraria from Janssen, BMS/Celgene, Amgen, Takeda, Sanofi, and GSK; participation on data safety monitoring or advisory board of Janssen, BMS-Celgene, Amgen, Takeda, Sanofi, and GSK. ML-P declares receiving consulting fees from Celgene/BMS; honoraria from Janssen and Kite/Gilead; and participation on data safety monitoring or advisory board from Celgene/BMS and Novartis. LGR-L declares honoraria from Janssen, GSK, Sanofi, and BMS; travel grants from Janssen, Amgen, GSK, Pfizer and Sanofi; and participation on data safety monitoring or advisory board from GSK and Sanofi. AS-S declares receiving travel grants from Jazz Pharmaceuticals, Pfizer, and MSD. JAP-S declares research and travel support Takeda, Abbvie, Gilead, AMGEN, Jazz, Alexion, Pierre Fabre and Beigene; educational activities, speaker, and advisory fees with Gilead, Jazz, Alexion, AMGEN, Novartis, Janssen, BMS, and MSD; and participation on data safety monitoring or advisory board from Gilead, Jazz, Alexion, AMGEN, Novartis, Janssen, BMS and MSD. BP reports research funding from BMS, GSK, Roche, Beigene, and Sanofi; consultancy fees from BMS, GSK, Janssen, Sanofi and Takeda; honoraria from Adaptive, Amgen, Becton Dickinson, BMS/Celgene, GSK, Janssen, Sanofi, and Roche; and support for attending meetings from GSK. FP declares receiving grants from the Spanish Ministry of Health (ISCIII) and the Government of Navarra; honoraria from Janssen, Oryzon, Dialectica, Novartis, Instituto Roche, Servier, ViviaBiotech, and Techspert; support for attending meetings or travel from Gilead, Celgene, and Janssen; and a leadership or fiduciary role in RICORS Terav and IDISNA. MJ declares receiving research or travel support by Fundació Bancaria la Caixa, ISCIII, and CellNex Teleom; honoraria from educational activities, speaker, and advisory roles with Miltenyi and indirectly with sponsors of congresses; and participation on data safety monitoring or advisory boards with MAB Gyala. JMM declares receiving honoriaria from Gilead/Kite, Novartis, BMS/Celgene, and Roche; travel grants, accommodation, and expenses from Jazz Pharma, Gilead-Kite, Janssen, and Sandoz; and consulting or advisory board fees in Jazz Pharma, Novartis, and Sandoz. M-VM declares honoraria derived from lectures and participation in advisory boards from Janssen, BMS/Celgene, Takeda, Amgen, GSK, Pfizer, Regeneron, Roche, and Sanofi. MP declares receiving honoraria from Thermofisher Scientific and LetiPharma. AU-I declares receiving grants from the Spanish Ministry of Health (ISCIII); honoraria for lectures from BMS and Gilead; support for attending meetings from Amgen; 23% of participation in ARI-002 patent ARI-001 patent in preparation; advisory board fees and participation in Miltenyi biomedicine; being coordinator of the Spanish group of CAR T-cell therapy. CFL declares receiving grants through his institution from BMS, Janssen, and Amgen; honoraria from Amgen, Janssen, BMS, GSK, and Sanofi; support for attending meetings or travel from Janssen, BMS, GSK, and Amgen; and participation in data safety monitoring or advisory boards with Janssen, BMS, Amgen, Pfizer, and Sanofi. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)- Published
- 2023
- Full Text
- View/download PDF
25. Clonal architecture and evolutionary history of Waldenström's macroglobulinemia at the single-cell level.
- Author
-
García-Sanz R, García-Álvarez M, Medina A, Askari E, González-Calle V, Casanova M, de la Torre-Loizaga I, Escalante-Barrigón F, Bastos-Boente M, Bárez A, Vidaña-Bedera N, Alonso JM, Sarasquete ME, González M, Chillón MC, Alcoceba M, and Jiménez C
- Subjects
- Humans, Single-Cell Analysis, Protein Array Analysis, Myeloid Differentiation Factor 88 genetics, DNA Mutational Analysis, Waldenstrom Macroglobulinemia diagnosis, Waldenstrom Macroglobulinemia genetics, Clonal Evolution, Mutation, DNA Copy Number Variations
- Abstract
To provide insight into the subclonal architecture and co-dependency patterns of the alterations in Waldenström's macroglobulinemia (WM), we performed single-cell mutational and protein profiling of eight patients. A custom panel was designed to screen for mutations and copy number alterations at the single-cell level in samples taken from patients at diagnosis (n=5) or at disease progression (n=3). Results showed that in asymptomatic WM at diagnosis, MYD88L265P was the predominant clonal alteration; other events, if present, were secondary and subclonal to MYD88L265P. In symptomatic WM, clonal diversity was more evident, uncovering combinations of alterations that synergized to promote clonal expansion and dominance. At disease progression, a dominant clone was observed, sometimes accompanied by other less complex minor clones, which could be consistent with a clonal selection process. Clonal diversity was also reduced, probably due to the effect of treatment. Finally, we combined protein expression with mutational analysis to map somatic genotype with the immunophenotype. Our findings provide a comprehensive view of the clonality of tumor populations in WM and how clonal complexity can evolve and impact disease progression., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2023. Published by The Company of Biologists Ltd.)
- Published
- 2023
- Full Text
- View/download PDF
26. Definition and Clinical Significance of the Monoclonal Gammopathy of Undetermined Significance-Like Phenotype in Patients With Monoclonal Gammopathies.
- Author
-
Burgos L, Tamariz-Amador LE, Puig N, Cedena MT, Guerrero C, Jelínek T, Johnson S, Milani P, Cordon L, Perez JJ, Lasa M, Termini R, Oriol A, Hernandez MT, Palomera L, Martinez-Martinez R, de la Rubia J, de Arriba F, Rios R, Gonzalez ME, Gironella M, Cabañas V, Casanova M, Krsnik I, Perez-Montaña A, González-Calle V, Rodriguez-Otero P, Maisnar V, Hajek R, Van Rhee F, Jimenez-Zepeda V, Palladini G, Merlini G, Orfao A, de la Cruz J, Martinez-Lopez J, Lahuerta JJ, Rosiñol L, Blade J, Mateos MV, San-Miguel JF, and Paiva B
- Subjects
- Humans, Clinical Relevance, Disease Progression, Phenotype, Monoclonal Gammopathy of Undetermined Significance diagnosis, Monoclonal Gammopathy of Undetermined Significance therapy, Immunoglobulin Light-chain Amyloidosis, Paraproteinemias diagnosis, Paraproteinemias therapy, Multiple Myeloma diagnosis
- Abstract
Purpose: The existence of patients with multiple myeloma (MM) and light-chain (AL) amyloidosis who present with a monoclonal gammopathy of undetermined significance (MGUS)-like phenotype has been hypothesized, but methods to identify this subgroup are not standardized and its clinical significance is not properly validated., Patients and Methods: An algorithm to identify patients having MGUS-like phenotype was developed on the basis of the percentages of total bone marrow (BM) plasma cells (PC) and of clonal PC within the BM PC compartment, determined at diagnosis using flow cytometry in 548 patients with MGUS and 2,011 patients with active MM. The clinical significance of the algorithm was tested and validated in 488 patients with smoldering MM, 3,870 patients with active MM and 211 patients with AL amyloidosis., Results: Patients with smoldering MM with MGUS-like phenotype showed significantly lower rates of disease progression (4.5% and 0% at 2 years in two independent series). There were no statistically significant differences in time to progression between treatment versus observation in these patients. In active newly diagnosed MM, MGUS-like phenotype retained independent prognostic value in multivariate analyses of progression-free survival (PFS; hazard ratio [HR], 0.49; P = .001) and overall survival (OS; HR, 0.56; P = .039), together with International Staging System, lactate dehydrogenase, cytogenetic risk, transplant eligibility, and complete remission status. Transplant-eligible patients with active MM with MGUS-like phenotype showed PFS and OS rates at 5 years of 79% and 96%, respectively. In this subgroup, there were no differences in PFS and OS according to complete remission and measurable residual disease status. Application of the algorithm in two independent series of patients with AL predicted for different survival., Conclusion: We developed an open-access algorithm for the identification of MGUS-like patients with distinct clinical outcomes. This phenotypic classification could become part of the diagnostic workup of MM and AL amyloidosis.
- Published
- 2023
- Full Text
- View/download PDF
27. Lenalidomide maintenance based on a genetic profile.
- Author
-
Mateos MV and González-Calle V
- Subjects
- Humans, Lenalidomide therapeutic use, Genetic Profile, Thalidomide therapeutic use, Multiple Myeloma, Hematopoietic Stem Cell Transplantation
- Published
- 2023
- Full Text
- View/download PDF
28. Multiple myeloma with t(11;14): impact of novel agents on outcome.
- Author
-
Puertas B, González-Calle V, Sobejano-Fuertes E, Escalante F, Rey-Bua B, Padilla I, García-Sanz R, Puig N, Gutiérrez NC, and Mateos MV
- Subjects
- Humans, Retrospective Studies, Disease-Free Survival, Prognosis, Chromosome Aberrations, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols, Multiple Myeloma drug therapy, Multiple Myeloma genetics
- Abstract
Multiple myeloma (MM) patients with t(11;14) present unique biological features and their prognosis is not well established. We report a retrospective study of 591 MM patients, 17.3% of whom had t(11;14). It was designed to determine the prognostic impact of this abnormality and the effect of novel agents on the response and outcomes. Three groups were established based on their cytogenetics: (1) t(11;14); (2) high-risk chromosomal abnormalities; and (3) standard risk (SR). After 80.1 months (1.2-273.8 months) of follow-up, no differences were observed in overall survival (OS) between the t(11;14) and SR groups (75.8 vs. 87.2 months; P = 0.438). Treatment of MM t(11;14) with novel agents did not improve their overall response rate (ORR) or complete response (CR) compared with those who received conventional therapy (ORR: 87.2 vs. 79.5%, P = 0.336; CR: 23.4 vs. 12.8%, P = 0.215). This effect translated into a similar PFS (39.6 vs. 30.0 months; P = 0.450) and OS (107.6 vs. 75.7 months; P = 0.175). In summary, MM t(11;14) patients did not benefit from the introduction of novel agents as much as SR patients did, indicating that other therapies are needed to improve their outcomes., (© 2023. The Author(s).)
- Published
- 2023
- Full Text
- View/download PDF
29. Novel Agents as Main Drivers for Continued Improvement in Survival in Multiple Myeloma.
- Author
-
Puertas B, González-Calle V, Sobejano-Fuertes E, Escalante F, Queizán JA, Bárez A, Labrador J, Alonso-Alonso JM, García de Coca A, Cantalapiedra A, Villaescusa T, Aguilar-Franco C, Alejo-Alonso E, Rey-Bua B, López-Corral L, García-Sanz R, Puig N, Gutiérrez NC, and Mateos MV
- Abstract
(1) Background: New therapeutic strategies have improved the prognosis of multiple myeloma (MM), changing the accepted view of this disease from being incurable to treatable. (2) Methods: We studied 1001 patients with MM between 1980 and 2020, grouping patients into ten-year periods by diagnosis 1980-1990, 1991-2000, 2001-2010 and 2011-2020. (3) Results: After 65.1 months of follow-up, the median OS of the cohort was 60.3 months, and OS increased significantly over time: 22.4 months in 1980-1990, 37.4 months in 1991-2000, 61.8 months in 2001-2010 and 103.6 months in 2011-2020 ( p < 0.001). Using novel agents in the front-line setting for myeloma patients yielded a significantly better OS than in those treated with conventional therapies, especially when combinations of at least two novel agents were used. The median OS of patients treated with the combination of at least two novel agents in induction was significantly prolonged compared to those treated with a single novel agent or conventional therapy in induction: 143.3 vs. 61.0 vs. 42.2 months ( p < 0.001). The improvement was apparent in all patients regardless of age at diagnosis. In addition, 132 (13.2%) patients were long-term survivors (median OS ≥ 10 years). Some independent clinical predictors of long-term survival were identified: ECOG < 1, age at diagnosis ≤ 65 years, non-IgA subtype, ISS-1 and standard-risk cytogenetic. Achieving CR and undergoing ASCT were positively associated with >10 years of survival. (4) Conclusions: The combination of novel agents appears to be the main factor for the improvement in survival in MM, which is becoming a chronic and even curable disease in a subtype of patients without high-risk features.
- Published
- 2023
- Full Text
- View/download PDF
30. Monoclonal gammopathy of renal significance (MGRS): Real-world data on outcomes and prognostic factors.
- Author
-
Gozzetti A, Guarnieri A, Zamagni E, Zakharova E, Coriu D, Bittrich M, Pika T, Tovar N, Schutz N, Ciofini S, Peña C, Rocchi S, Rassner M, Avivi I, Waszczuk-Gajda A, Chhabra S, Usnarska-Zubkiewicz L, González-Calle V, Mateos MV, Bocchia M, Bigi F, Füllgraf H, Bhasin-Chhabra B, Gentile M, Davila J, Vesole DH, Cavo M, Thapa B, Crusoe E, Einsele H, Legiec W, Charliński G, and Jurczyszyn A
- Subjects
- Adult, Aged, Humans, Prognosis, Retrospective Studies, Transplantation, Autologous adverse effects, Hematopoietic Stem Cell Transplantation adverse effects, Kidney Diseases etiology, Kidney Diseases pathology, Kidney Diseases therapy, Monoclonal Gammopathy of Undetermined Significance complications, Monoclonal Gammopathy of Undetermined Significance diagnosis, Monoclonal Gammopathy of Undetermined Significance therapy, Paraproteinemias diagnosis, Precancerous Conditions
- Abstract
Monoclonal gammopathy of renal significance (MGRS) is a recognized clinical entity. Literature regarding treatment and its outcomes in MGRS is sparse due to the rarity and misdiagnosis of MGRS. We retrospectively analyzed 280 adults with an MGRS diagnosis from 2003 to 2020 across 19 clinical centers from 12 countries. All cases required renal biopsy for the pathological diagnosis of MGRS. Amyloidosis-related to MGRS (MGRS-A) was present in 180 patients; nonamyloidosis MGRS (MGRS-NA), including a broad spectrum of renal pathologies, was diagnosed in 100 patients. The median overall survival in the studied cohort was 121.0 months (95% CI: 105.0-121.0). Patients with MGRS-A had a shorter overall survival than patients with MGRS-NA (HR = 0.41, 95%CI: 0.25-0.69; p = 0.0007). Both hematologic and renal responses were associated with longer survival. Achievement of ≥VGPR was generally predictive of a renal response (OR = 8.03 95%CI: 4.04-115.96; p < 0.0001), one-fourth of patients with ≥VGPR were renal nonresponders. In MGRS-A, factors associated with poor prognosis included elevated levels of creatinine, beta-2-microglobulin, and hemodialysis at diagnosis. In MGRS-NA, only age >65 years was associated with increased risk of death. Treatments provided similar hematologic response rates in both types of MGRS. Autologous stem cell transplantation led to better response than other treatments. This multicenter and international effort is currently the largest report on MGRS., (© 2022 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)
- Published
- 2022
- Full Text
- View/download PDF
31. Recovery of polyclonal immunoglobulins during treatment in patients ineligible for autologous stem-cell transplantation is a prognostic marker of longer progression-free survival and overall survival.
- Author
-
Dávila J, González-Calle V, Escalante F, Cerdá S, Puig N, García-Sanz R, Bárez A, Montes C, López R, Alonso JM, Aguilar C, García-Mateo A, Labrador J, Aguilera C, García-Coca A, Hernández R, Mateos MV, and Ocio EM
- Subjects
- Disease-Free Survival, Humans, Immunoglobulins, Prognosis, Progression-Free Survival, Retrospective Studies, Transplantation, Autologous, Hematopoietic Stem Cell Transplantation, Multiple Myeloma diagnosis
- Abstract
Immunoparesis is the suppression of normal polyclonal immunoglobulins and is present in most patients with newly diagnosed multiple myeloma (MM). The association of immunoparesis at diagnosis, and particularly its recovery along with treatment, with survival in patients ineligible for autologous stem-cell transplantation (ASCT) has not been well established. This retrospective study evaluated the impact of immunoparesis in 431 patients diagnosed with MM, ineligible for ASCT, with a median overall survival of 36 months [95% confidence interval (CI): 31-40]. Immunoparesis was present in 81.2% of patients at diagnosis and was associated with a trend to a worse overall response rate (ORR: 84.8% vs. 74.9%; OR 1.88 (95% CI: 0.97-3.63), shorter progression-free survival (PFS) [22.0 vs. 18.2 months; hazard ratio (HR) 0.775; 95%CI: 0.590-1.018; p = 0.066], and overall survival (OS) (45.9 vs. 34.2 months; HR 0.746; 95% CI: 0.551-1.010; p = 0.057). Twenty-four per cent of patients who had immunoparesis at diagnosis recovered polyclonal immunoglobulins in the follow-up period. Interestingly, these patients had a better ORR (96.3% vs. 68.2%; OR 12.29 (95% CI: 3.77-40.06), PFS (HR 0.703; 95CI%: 0.526-0.941; p = 0.018) and OS (HR 0.678; 95 CI%: 0.503-0.913; p = 0.011) than patients who did not recover it. In summary, restoring a healthy immune system along with first-line treatment in patients with MM, not receiving ASCT, is associated with better outcomes., (© 2022 British Society for Haematology and John Wiley & Sons Ltd.)
- Published
- 2022
- Full Text
- View/download PDF
32. Interlaboratory Analytical Validation of a Next-Generation Sequencing Strategy for Clonotypic Assessment and Minimal Residual Disease Monitoring in Multiple Myeloma.
- Author
-
Medina A, Jiménez C, Puig N, Sarasquete ME, Flores-Montero J, García-Álvarez M, Prieto-Conde I, Chillón C, Alcoceba M, González-Calle V, Gutiérrez NC, Jacobsen A, Vigil E, Hutt K, Huang Y, Orfao A, González M, Miller J, and García-Sanz R
- Subjects
- Humans, High-Throughput Nucleotide Sequencing methods, Neoplasm, Residual diagnosis, Neoplasm, Residual genetics, Reproducibility of Results, Multiple Myeloma diagnosis, Multiple Myeloma genetics
- Abstract
Context.—: Minimal residual disease (MRD) is a major prognostic factor in multiple myeloma, although validated technologies are limited., Objective.—: To standardize the performance of the LymphoTrack next-generation sequencing (NGS) assays (Invivoscribe), targeting clonal immunoglobulin rearrangements, in order to reproduce the detection of tumor clonotypes and MRD quantitation in myeloma., Design.—: The quantification ability of the assay was evaluated through serial dilution experiments. Paired samples from 101 patients were tested by LymphoTrack, using Sanger sequencing and EuroFlow's next-generation flow (NGF) assay as validated references for diagnostic and follow-up evaluation, respectively. MRD studies using LymphoTrack were performed in parallel at 2 laboratories to evaluate reproducibility., Results.—: Sensitivity was set as 1.3 tumor cells per total number of input cells. Clonality was confirmed in 99% and 100% of cases with Sanger and NGS, respectively, showing great concordance (97.9%), although several samples had minor discordances in the nucleotide sequence of rearrangements. Parallel NGS was performed in 82 follow-up cases, achieving a median sensitivity of 0.001%, while for NGF, median sensitivity was 0.0002%. Reproducibility of LymphoTrack-based MRD studies (85.4%) and correlation with NGF (R2 > 0.800) were high. Bland-Altman tests showed highly significant levels of agreement between flow and sequencing., Conclusions.—: Taken together, we have shown that LymphoTrack is a suitable strategy for clonality detection and MRD evaluation, with results comparable to gold standard procedures.
- Published
- 2022
- Full Text
- View/download PDF
33. Mass spectrometry vs immunofixation for treatment monitoring in multiple myeloma.
- Author
-
Puig N, Contreras MT, Agulló C, Martínez-López J, Oriol A, Blanchard MJ, Ríos R, Martín J, Iñigo MB, Sureda A, Hernández MT, de la Rubia J, González-Calle V, Krsnik I, Cabañas V, Palomera L, Moraleda JM, Bargay J, Cedena MT, Paiva B, Rosiñol L, Bladé J, San Miguel J, Lahuerta JJ, and Mateos MV
- Subjects
- Antibodies, Monoclonal, Humans, Immunoglobulin Light Chains, Mass Spectrometry, Transplantation, Autologous, Hematopoietic Stem Cell Transplantation, Multiple Myeloma diagnosis, Multiple Myeloma therapy
- Abstract
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. This trial was registered at www.clinicaltrials.gov as #NCT01916252., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
34. MYD88 Mutations: Transforming the Landscape of IgM Monoclonal Gammopathies.
- Author
-
Alcoceba M, García-Álvarez M, Medina A, Maldonado R, González-Calle V, Chillón MC, Sarasquete ME, González M, García-Sanz R, and Jiménez C
- Subjects
- Aged, Humans, Immunoglobulin M genetics, Immunoglobulin M metabolism, Lymphoma genetics, Lymphoma metabolism, Lymphoma, B-Cell genetics, Lymphoma, B-Cell metabolism, Mutation, Myeloid Differentiation Factor 88 genetics, Myeloid Differentiation Factor 88 metabolism, Waldenstrom Macroglobulinemia diagnosis, Waldenstrom Macroglobulinemia genetics, Waldenstrom Macroglobulinemia metabolism
- Abstract
The MYD88 gene has a physiological role in the innate immune system. Somatic mutations in MYD88 , including the most common L265P, have been associated with the development of certain types of lymphoma. MYD88
L265P is present in more than 90% of patients with Waldenström's macroglobulinemia (WM) and IgM monoclonal gammopathy of undetermined significance (IgM-MGUS). The absence of MYD88 mutations in WM patients has been associated with a higher risk of transformation into aggressive lymphoma, resistance to certain therapies (BTK inhibitors), and shorter overall survival. The MyD88 signaling pathway has also been used as a target for specific therapies. In this review, we summarize the clinical applications of MYD88 testing in the diagnosis, prognosis, follow-up, and treatment of patients. Although MYD88L265P is not specific to WM, few tumors present a single causative mutation in a recurrent position. The role of the oncogene in the pathogenesis of WM is still unclear, especially considering that the mutation can be found in normal B cells of patients, as recently reported. This may have important implications for early lymphoma detection in healthy elderly individuals and for the treatment response assessment based on a MYD88L265P analysis.- Published
- 2022
- Full Text
- View/download PDF
35. Anti-BCMA CAR T-cell Therapy: Changing the Natural History of Multiple Myeloma.
- Author
-
Puertas B, Mateos MV, and González-Calle V
- Published
- 2022
- Full Text
- View/download PDF
36. High-risk multiple myeloma: how to treat at diagnosis and relapse?
- Author
-
Mateos MV, Martínez BP, and González-Calle V
- Subjects
- Antineoplastic Agents therapeutic use, Disease Management, Frailty diagnosis, Frailty epidemiology, Frailty therapy, Humans, Immunotherapy, Adoptive, Male, Middle Aged, Multiple Myeloma diagnosis, Multiple Myeloma epidemiology, Neoplasm Recurrence, Local diagnosis, Neoplasm Recurrence, Local epidemiology, Risk Assessment, Risk Factors, Severity of Illness Index, Multiple Myeloma therapy, Neoplasm Recurrence, Local therapy
- Abstract
Patients with multiple myeloma have experienced a great improvement in survival over the past century because of the introduction of novel therapeutic strategies. However, a subgroup of patients with poorer outcomes than expected is considered high risk and identified by the presence of patient- and disease-based factors such as frailty, extramedullary disease, cytogenetic abnormalities, or even relapses occurring earlier than expected according to the baseline factors. Although the management of patients with high-risk features is not well established because of the lack of specific trials in this subgroup of patients and because of their underrepresentation in the clinical trials, treatment should be planned on 2 pillars: (1) poor prognosis with the presence of high-risk features can be at least improved or even abrogated by achieving a deep and sustained response over time, and (2) this can most likely be obtained through using the best therapeutic options and in a response-adapted way. Some clinical trials that have been planned or are ongoing include only patients with high-risk features, using the most effective therapies (proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies) as well as chimeric antigen receptor T cells and T-cell engagers that will unravel what the best therapeutic approach will be to overcome the poor prognosis of the presence of high-risk features., (Copyright © 2021 by The American Society of Hematology.)
- Published
- 2021
- Full Text
- View/download PDF
37. Liquid biopsy: a non-invasive approach for Hodgkin lymphoma genotyping.
- Author
-
Alcoceba M, García-Álvarez M, Chillón MC, Jiménez C, Medina A, Antón A, Blanco O, Díaz LG, Tamayo P, González-Calle V, Vidal MJ, Cuello R, Díaz Gálvez FJ, Queizán JA, Martín A, González M, García-Sanz R, and Sarasquete ME
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Alleles, Female, Genotype, High-Throughput Nucleotide Sequencing, Hodgkin Disease blood, Humans, Male, Middle Aged, Mutation, Prognosis, Prospective Studies, Young Adult, DNA, Neoplasm blood, Genotyping Techniques, Hodgkin Disease genetics, Liquid Biopsy
- Abstract
The Hodgkin lymphoma (HL) genomic landscape is hardly known due to the scarcity of tumour cells in the tissue. Liquid biopsy employing circulating tumour DNA (ctDNA) can emerge as an alternative tool for non-invasive genotyping. By using a custom next generation sequencing (NGS) panel in combination with unique molecule identifiers, we aimed to identify somatic variants in the ctDNA of 60 HL at diagnosis. A total of 277 variants were detected in 36 of the 49 samples (73·5%) with a good quality ctDNA sample. The median number of variants detected per patient was five (range 1-23) with a median variant allele frequency of 4·2% (0·84-28%). Genotyping revealed somatic variants in the following genes: SOCS1 (28%), IGLL5 (26%), TNFAIP3 (23%), GNA13 (23%), STAT6 (21%) and B2M (19%). Moreover, several poor prognosis features (high LDH, low serum albumin, B-symptoms, IPI ≥ 3 or at an advanced stage) were related to significantly higher amounts of ctDNA. Variant detection in ctDNA by NGS is a feasible approach to depict the genetic features of HL patients at diagnosis. Our data favour the implementation of liquid biopsy genotyping for the routine evaluation of HL patients., (© 2021 British Society for Haematology and John Wiley & Sons Ltd.)
- Published
- 2021
- Full Text
- View/download PDF
38. Lenalidomide and dexamethasone with or without clarithromycin in patients with multiple myeloma ineligible for autologous transplant: a randomized trial.
- Author
-
Puig N, Hernández MT, Rosiñol L, González E, de Arriba F, Oriol A, González-Calle V, Escalante F, de la Rubia J, Gironella M, Ríos R, García-Sánchez R, Arguiñano JM, Alegre A, Martín J, Gutiérrez NC, Calasanz MJ, Martín ML, Couto MDC, Casanova M, Arnao M, Pérez-Persona E, Garzón S, González MS, Martín-Sánchez G, Ocio EM, Coleman M, Encinas C, Vale AM, Teruel AI, Cortés-Rodríguez M, Paiva B, Cedena MT, San-Miguel JF, Lahuerta JJ, Bladé J, Niesvizky R, and Mateos MV
- Subjects
- Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols adverse effects, Clarithromycin adverse effects, Dexamethasone adverse effects, Female, Hematopoietic Stem Cell Transplantation, Humans, Lenalidomide adverse effects, Male, Transplantation, Autologous, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Clarithromycin therapeutic use, Dexamethasone therapeutic use, Lenalidomide therapeutic use, Multiple Myeloma drug therapy
- Abstract
Although case-control analyses have suggested an additive value with the association of clarithromycin to continuous lenalidomide and dexamethasone (Rd), there are not phase III trials confirming these results. In this phase III trial, 286 patients with MM ineligible for ASCT received Rd with or without clarithromycin until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). With a median follow-up of 19 months (range, 0-54), no significant differences in the median PFS were observed between the two arms (C-Rd 23 months, Rd 29 months; HR 0.783, p = 0.14), despite a higher rate of complete response (CR) or better in the C-Rd group (22.6% vs 14.4%, p = 0.048). The most common G3-4 adverse events were neutropenia [12% vs 19%] and infections [30% vs 25%], similar between the two arms; however, the percentage of toxic deaths was higher in the C-Rd group (36/50 [72%] vs 22/40 [55%], p = 0.09). The addition of clarithromycin to Rd in untreated transplant ineligible MM patients does not improve PFS despite increasing the ≥CR rate due to the higher number of toxic deaths in the C-Rd arm. Side effects related to overexposure to steroids due to its delayed clearance induced by clarithromycin in this elderly population could explain these results. The trial was registered in clinicaltrials.gov with the name GEM-CLARIDEX: Ld vs BiRd and with the following identifier NCT02575144. The full trial protocol can be accessed from ClinicalTrials.gov. This study received financial support from BMS/Celgene.
- Published
- 2021
- Full Text
- View/download PDF
39. Genetic complexity impacts the clinical outcome of follicular lymphoma patients.
- Author
-
García-Álvarez M, Alonso-Álvarez S, Prieto-Conde I, Jiménez C, Sarasquete ME, Chillón MC, Medina A, Balanzategui A, Maldonado R, Antón A, Rodríguez M, Blanco O, Díaz LG, Tamayo P, Blanco P, Esteban C, González-Calle V, Puig N, Gutiérrez N, Martín A, García-Sanz R, González M, Caballero MD, and Alcoceba M
- Subjects
- Humans, Translocation, Genetic, Lymphoma, Follicular diagnosis, Lymphoma, Follicular genetics
- Published
- 2021
- Full Text
- View/download PDF
40. Pembrolizumab as Consolidation Strategy in Patients with Multiple Myeloma: Results of the GEM-Pembresid Clinical Trial.
- Author
-
Puig N, Corchete-Sánchez LA, Pérez-Morán JJ, Dávila J, Paíno T, de la Rubia J, Oriol A, Martín-Sánchez J, de Arriba F, Bladé J, Blanchard MJ, González-Calle V, García-Sanz R, Paiva B, Lahuerta JJ, San-Miguel JF, Mateos MV, and Ocio EM
- Abstract
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.- Published
- 2020
- Full Text
- View/download PDF
41. International Myeloma Working Group risk stratification model for smoldering multiple myeloma (SMM).
- Author
-
Mateos MV, Kumar S, Dimopoulos MA, González-Calle V, Kastritis E, Hajek R, De Larrea CF, Morgan GJ, Merlini G, Goldschmidt H, Geraldes C, Gozzetti A, Kyriakou C, Garderet L, Hansson M, Zamagni E, Fantl D, Leleu X, Kim BS, Esteves G, Ludwig H, Usmani S, Min CK, Qi M, Ukropec J, Weiss BM, Rajkumar SV, Durie BGM, and San-Miguel J
- Subjects
- Aged, Disease Progression, Female, Follow-Up Studies, Humans, Male, Middle Aged, Risk Factors, Biomarkers, Tumor blood, Immunoglobulin Light Chains blood, Models, Biological, Multiple Myeloma blood, Myeloma Proteins metabolism
- Abstract
Smoldering multiple myeloma (SMM) is an asymptomatic precursor state of multiple myeloma (MM). Recently, MM was redefined to include biomarkers predicting a high risk of progression from SMM, thus necessitating a redefinition of SMM and its risk stratification. We assembled a large cohort of SMM patients meeting the revised IMWG criteria to develop a new risk stratification system. We included 1996 patients, and using stepwise selection and multivariable analysis, we identified three independent factors predicting progression risk at 2 years: serum M-protein >2 g/dL (HR: 2.1), involved to uninvolved free light-chain ratio >20 (HR: 2.7), and marrow plasma cell infiltration >20% (HR: 2.4). This translates into 3 categories with increasing 2-year progression risk: 6% for low risk (38%; no risk factors, HR: 1); 18% for intermediate risk (33%; 1 factor; HR: 3.0), and 44% for high risk (29%; 2-3 factors). Addition of cytogenetic abnormalities (t(4;14), t(14;16), +1q, and/or del13q) allowed separation into 4 groups (low risk with 0, low intermediate risk with 1, intermediate risk with 2, and high risk with ≥3 risk factors) with 6, 23, 46, and 63% risk of progression in 2 years, respectively. The 2/20/20 risk stratification model can be easily implemented to identify high-risk SMM for clinical research and routine practice and will be widely applicable.
- Published
- 2020
- Full Text
- View/download PDF
42. Different MAF translocations confer similar prognosis in newly diagnosed multiple myeloma patients.
- Author
-
Goldman-Mazur S, Jurczyszyn A, Castillo JJ, Waszczuk-Gajda A, Grząśko N, Radocha J, Bittrich M, Kortüm KM, Gozzetti A, Usnarska-Zubkiewicz L, Valls JD, Jayabalan DS, Niesvizky R, Kelman J, Coriu D, Rosiñol L, Szukalski Ł, González-Calle V, Mateos MV, Jamroziak K, Hus I, Avivi I, Cohen Y, Mazur P, Suska A, Chappell A, Madduri D, Chhabra S, Kleman A, Hari P, Delforge M, Robak P, Gentile M, Kozłowska I, Goldberg SL, Czepiel J, Długosz-Danecka M, Silbermann R, Olszewski AJ, Barth P, Mikala G, Chim CS, and Vesole DH
- Subjects
- Disease-Free Survival, Humans, Prognosis, Retrospective Studies, Transplantation, Autologous, Treatment Outcome, Hematopoietic Stem Cell Transplantation, Multiple Myeloma diagnosis, Multiple Myeloma genetics, Multiple Myeloma therapy
- Abstract
The MAF translocations, t(14;16) and t(14;20), are considered as adverse prognostic factors based on few studies with small sample sizes. We report on their prognostic impact in a large group of 254 patients - 223 (87.8%) with t(14;16) and 31 (12.2%) with t(14;20). There were no intergroup differences in survival estimates. Median progression-free survival was 16.6 months for t(14;16) and 24.9 months for t(14;20) ( p = 0.28). Median overall survival (OS) was 54.0 months and 49.0 months, respectively ( p = 0.62). Median OS in patients who underwent double autologous stem cell transplantation (ASCT) was 107.0 months versus 60.0 months in patients who received single ASCT ( p < 0.001). ISS 3 was associated with shorter OS (HR = 1.89; 95% CI 1.24-3.19; p = 0.005) in Cox analysis. Our study suggests that t(14;20) should be considered as an adverse factor of equal prognostic implication to t(14;16).
- Published
- 2020
- Full Text
- View/download PDF
43. Is there a role for new drugs with alkylating properties in multiple myeloma?
- Author
-
Mateos MV and González-Calle V
- Subjects
- Antineoplastic Agents, Alkylating, Humans, Melphalan, Multiple Myeloma
- Published
- 2020
- Full Text
- View/download PDF
44. A multicenter retrospective study of 223 patients with t(14;16) in multiple myeloma.
- Author
-
Goldman-Mazur S, Jurczyszyn A, Castillo JJ, Waszczuk-Gajda A, Grząśko N, Radocha J, Bittrich M, Kortüm KM, Gozzetti A, Usnarska-Zubkiewicz L, Davila Valls J, Jayabalan DS, Niesvizky R, Kelman J, Coriu D, Rosiñol L, Szukalski Ł, González-Calle V, Mateos MV, Jamroziak K, Hus I, Avivi I, Cohen Y, Suska A, Chappell A, Madduri D, Chhabra S, Kleman A, Hari P, Delforge M, Robak P, Gentile M, Kozłowska I, Goldberg SL, Czepiel J, Silbermann R, Olszewski AJ, Barth P, Mikala G, Chim CS, Długosz-Danecka M, Grosicki S, and Vesole DH
- Subjects
- Female, Humans, Male, Middle Aged, Multiple Myeloma mortality, Progression-Free Survival, Retrospective Studies, Translocation, Genetic, Multiple Myeloma genetics
- Abstract
The t(14;16) translocation, found in 3%-5% of newly diagnosed (ND) multiple myeloma (MM), has been associated with adverse outcomes. However, the studies establishing the characteristics of t(14;16) included solely small cohorts. The goal of the current international, multicenter (n = 25 centers), retrospective study was to describe the characteristics and outcomes of t(14;16) patients in a large, real-world cohort (n = 223). A substantial fraction of patients had renal impairment (24%) and hemoglobin <10 g/dL (56%) on initial presentation. Combined therapy of both immunomodulatory drug and proteasome inhibitor (PI) in the first line was used in 35% of patients. Autologous stem cell transplantation was performed in 42% of patients. With a median follow up of 4.1 years (95% CI 3.7-18.7), the median progression-free survival (PFS) and overall survival (OS) from first line therapy were 2.1 years (95% CI 1.5-2.4) and 4.1 years (95% CI 3.3-5.5), respectively. Worse OS was predicted by age > 60 years (HR = 1.65, 95% CI [1.05-2.58]), as well as revised International Scoring System (R-ISS) 3 (vs R-ISS 2; HR = 2.59, 95% CI [1.59-4.24]). In conclusion, based on the largest reported cohort of t(14;16) patients, quarter of this subset of MM patients initially presents with renal failure, while older age and the R-ISS 3 predict poor survival., (© 2020 Wiley Periodicals, Inc.)
- Published
- 2020
- Full Text
- View/download PDF
45. Molecular profiling of immunoglobulin heavy-chain gene rearrangements unveils new potential prognostic markers for multiple myeloma patients.
- Author
-
Medina A, Jiménez C, Sarasquete ME, González M, Chillón MC, Balanzategui A, Prieto-Conde I, García-Álvarez M, Puig N, González-Calle V, Alcoceba M, Cuenca I, Barrio S, Escalante F, Gutiérrez NC, Gironella M, Hernández MT, Sureda A, Oriol A, Bladé J, Lahuerta JJ, San Miguel JF, Mateos MV, Martínez-López J, Calasanz MJ, and García-Sanz R
- Subjects
- Adult, Aged, Aged, 80 and over, Female, Follow-Up Studies, Gene Expression Profiling, Humans, Male, Middle Aged, Multigene Family, Multiple Myeloma immunology, Prognosis, Biomarkers, Tumor genetics, Gene Expression Regulation, Neoplastic, Gene Rearrangement, Immunoglobulin Heavy Chains genetics, Immunoglobulin Variable Region genetics, Multiple Myeloma genetics, Multiple Myeloma pathology
- Abstract
Multiple myeloma is a heterogeneous disease whose pathogenesis has not been completely elucidated. Although B-cell receptors play a crucial role in myeloma pathogenesis, the impact of clonal immunoglobulin heavy-chain features in the outcome has not been extensively explored. Here we present the characterization of complete heavy-chain gene rearrangements in 413 myeloma patients treated in Spanish trials, including 113 patients characterized by next-generation sequencing. Compared to the normal B-cell repertoire, gene selection was biased in myeloma, with significant overrepresentation of IGHV3, IGHD2 and IGHD3, as well as IGHJ4 gene groups. Hypermutation was high in our patients (median: 8.8%). Interestingly, regarding patients who are not candidates for transplantation, a high hypermutation rate (≥7%) and the use of IGHD2 and IGHD3 groups were associated with improved prognostic features and longer survival rates in the univariate analyses. Multivariate analysis revealed prolonged progression-free survival rates for patients using IGHD2/IGHD3 groups (HR: 0.552, 95% CI: 0.361-0.845, p = 0.006), as well as prolonged overall survival rates for patients with hypermutation ≥7% (HR: 0.291, 95% CI: 0.137-0.618, p = 0.001). Our results provide new insights into the molecular characterization of multiple myeloma, highlighting the need to evaluate some of these clonal rearrangement characteristics as new potential prognostic markers.
- Published
- 2020
- Full Text
- View/download PDF
46. A New Next-Generation Sequencing Strategy for the Simultaneous Analysis of Mutations and Chromosomal Rearrangements at DNA Level in Acute Myeloid Leukemia Patients.
- Author
-
Prieto-Conde MI, Corchete LA, García-Álvarez M, Jiménez C, Medina A, Balanzategui A, Hernández-Ruano M, Maldonado R, Sarasquete ME, Alcoceba M, Puig N, González-Calle V, García-Sanz R, Gutiérrez NC, González-Díaz M, and Chillón MC
- Subjects
- Base Sequence, Bone Marrow, Chromosome Breakpoints, DNA Mutational Analysis methods, Data Accuracy, Humans, In Situ Hybridization, Fluorescence methods, Karyotyping methods, Real-Time Polymerase Chain Reaction methods, Sensitivity and Specificity, Sequence Analysis, DNA methods, Chromosome Aberrations, DNA genetics, High-Throughput Nucleotide Sequencing methods, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Leukemia, Myeloid, Acute genetics, Mutation, Missense
- Abstract
Acute myeloid leukemias (AMLs) are currently genomically characterized by karyotype, fluorescence in situ hybridization (FISH), real-time quantitative PCR, and DNA sequencing. Next-generation sequencing offers the promise of detecting all genomic lesions in a single run. However, technical limitations have hampered the detection of chromosomal rearrangements, so most studies are limited to somatic mutation assessment or require the use of RNA-based strategies. To overcome these limitations, we designed a targeted-DNA capture next-generation sequencing approach associated with easy-to-perform public bioinformatic tools for one-step identification of translocations, inversions, and somatic mutations in AML. Thirty well-characterized newly diagnosed myeloid leukemia patients (27 AML and 3 chronic myeloid leukemia) were tested with the panel. Twenty-three of 24 known rearrangements, as well as one novel fusion gene that could not be detected by karyotype/fluorescence in situ hybridization/real-time quantitative PCR, were detected. This strategy also identified all chromosomal breakpoints as potential targets for future high-sensitive minimal residual disease studies. In addition, mutation analysis revealed the presence of missense protein-coding alterations in at least 1 of the 32 genes evaluated in 21 of 30 patients (70%). This strategy may represent a time- and cost-effective diagnostic method for molecular characterization in AML., (Copyright © 2020 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2020
- Full Text
- View/download PDF
47. EHA evaluation of the ESMO-Magnitude of Clinical Benefit Scale version 1.1 (ESMO-MCBS v1.1) for haematological malignancies.
- Author
-
Kiesewetter B, Cherny NI, Boissel N, Cerisoli F, Dafni U, de Vries EGE, Ghia P, Gökbuget N, González-Calle V, Huntly B, Jäger U, Latino NJ, Douillard JY, Malcovati L, Mateos MV, Ossenkoppele GJ, Porkka K, Raderer M M.D, Ribera JM, Scarfò L, Wester R, Zygoura P, and Sonneveld P
- Subjects
- Humans, Hematologic Neoplasms epidemiology, Outcome Assessment, Health Care methods, Societies, Medical organization & administration
- Abstract
Objective: Value frameworks in oncology have not been validated for the assessment of treatments in haematological malignancies, but to avoid overlaps and duplications it appears reasonable to build up experience on existing value frameworks, such as the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS)., Methods: Here we present the results of the first feasibility testing of the ESMO-MCBS v1.1 for haematological malignancies based on the grading of 80 contemporary studies for acute leukaemia, chronic leukaemia, lymphoma, myeloma and myelodysplastic syndromes. The aims were (1) to evaluate the scorability of data, (2) to evaluate the reasonableness of the generated grades for clinical benefit using the current version and (3) to identify shortcomings in the ESMO-MCBS v1.1 that require amendments to improve the efficacy and validity of the scale in grading new treatments in the management of haematological malignancies., Results: In general, the ESMO-MCBS v1.1 was found to be widely applicable to studies in haematological malignancies, generating scores that were judged as reasonable by European Hematology Association (EHA) experts. A small number of studies could either not be graded or were not appropriately graded. The reasons, related to the differences between haematological and solid tumour malignancies, are identified and described., Conclusions: Based on the findings of this study, ESMO and EHA are committed to develop a version of the ESMO-MCBS that is validated for haematological malignancies. This development process will incorporate all of the usual stringencies for accountability of reasonableness that have characterised the development of the ESMO-MCBS including field testing, statistical modelling, evaluation for reasonableness and openness to appeal and revision. Applying such a scale will support future public policy decision-making regarding the value of new treatments for haematological malignancies and will provide insights that could be helpful in the design of future clinical trials., Competing Interests: Competing interests: BK has received honoraria for lectures from Celgene and Novartis; NB has received honoraria for consulting and advisory role from Ariad, Amgen, Novartis and Pfizer; EGEdV declares advisory role for Daiichi Sankyo, Merck, NSABP, Pfizer, Sanofi and Synthon, and institutional financial support for clinical trials or contracted research for Amgen, AstraZeneca, Bayer, Chugai, CytomX Therapeutics, G1 Therapeutics, Genentech, Nordic Nanovector, Radius Health, Roche and Synthon; PG has received honoraria for lectures/advisory boards and research funding from AbbVie/Pharmacyclics, Acerta/AstraZeneca, BeiGene, Janssen, Gilead, Novartis, Sunesis and Verastem; NG has received honoraria for lectures, advisory boards and research support from Amgen, Pfizer and Incyte; VG-C has received honoraria for lectures from Janssen and for participation in advisory boards from Prothena; BH has received honoraria for lectures from Novartis, Pfizer and BMS, and for participation in advisory boards from Novartis, GlaxoSmithKline, Abbvie, Pfizer, BMS and Incyte; UJ has declared honoraria from Abbvie, BMS, Celgene, Amgen, Roche, Novartis, Gilead, Bioverativ, Janssen, MSD, Sandoz, Takeda and Pfizer; M-VM has received honoraria for lectures from Janssen, Celgene, Takeda and Amgen, and for participation in advisory boards from Janssen, Celgene, Takeda, Amgen, AbbVie, GlaxoSmithKline and PharmaMar; MR has received honoraria for lectures from Novarits, Ipsen, Celgene and Eisai; LS has received honoraria for lectures from Janssen, AbbVie, AstraZeneca, and for participation in advisory boards from Janssen; PS has received honoraria for lectures and advisory boards from Celgene, Janssen, Takeda and Amgen, and research support from Celgene, Janssen and Amgen., (© Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology.)
- Published
- 2020
- Full Text
- View/download PDF
48. Immunoglobulin gene rearrangement IGHV3-48 is a predictive marker of histological transformation into aggressive lymphoma in follicular lymphomas.
- Author
-
García-Álvarez M, Alonso-Álvarez S, Prieto-Conde I, Jiménez C, Sarasquete ME, Chillón MC, Medina A, Balanzategui A, Maldonado R, Antón A, Puig N, Rodríguez M, Blanco O, Tamayo P, González-Calle V, Martín A, García-Sanz R, González M, Caballero MD, and Alcoceba M
- Subjects
- Adult, Aged, Aged, 80 and over, Biomarkers, Tumor genetics, Female, Humans, Lymphoma, Follicular immunology, Lymphoma, Large B-Cell, Diffuse immunology, Male, Middle Aged, Prognosis, Young Adult, Gene Rearrangement, B-Lymphocyte, Heavy Chain, Genes, Immunoglobulin Heavy Chain, Immunoglobulin Variable Region, Lymphoma, Follicular genetics, Lymphoma, Follicular pathology, Lymphoma, Large B-Cell, Diffuse genetics, Lymphoma, Large B-Cell, Diffuse pathology
- Abstract
Follicular lymphoma (FL) is a heterogeneous disease whose pathogenesis remains partially unknown. Around 20% of FL patients experience early progression or treatment-refractory disease and 2-3% of patients per year experience histological transformation (HT) into a more aggressive lymphoma (tFL). Here, we evaluate the immunoglobulin heavy chain variable (IGHV) gene usage and mutational status in 187 FL cases to assess its impact on clinical outcome and histological transformation. The IGHV gene repertoire was remarkably biased in FL. The IGHV4-34 (14%), IGHV3-23 (14%), IGHV3-48 (10%), IGHV3-30 (9%) and IGHV3-21 (7%) genes accounted for more than half of the whole cohort. IGHV3-48 was overrepresented in cases of tFL (19%) compared with non-transformed FL at 5 years (5%, P = 0.05). Patients with the IGHV3-48 gene were significantly more likely to have had HT after 10 years than those who used other genes (71% vs. 25%, P < 0.05), irrespective of the therapy they received. Moreover, IGHV3-30 was also overrepresented in cases of FL (9%) and tFL (13%) compared with diffuse large B-cell lymphoma in which it was nearly absent. In conclusion, our results indicate a role for antigen selection in the development of FL, while the use of IGHV3-48 could help predict histological transformation.
- Published
- 2019
- Full Text
- View/download PDF
49. Drug-induced Thrombotic Microangiopathy During Maintenance Treatment in a Patient With Multiple Myeloma.
- Author
-
Higuero Saavedra V, González-Calle V, Sobejano E, Sebastiá J, Cabrero M, Bastida JM, Puig N, Ocio EM, and Mateos MV
- Published
- 2019
- Full Text
- View/download PDF
50. Improving the conditioning regimen in multiple myeloma.
- Author
-
Mateos MV and González-Calle V
- Subjects
- Clinical Trials as Topic, Female, Humans, Male, Treatment Outcome, Hematopoietic Stem Cell Transplantation methods, Multiple Myeloma therapy, Transplantation Conditioning
- Published
- 2019
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.