المؤلفون: Ríos-Tamayo, Rafael, Soler, Juan Alfons, García-Sánchez, Ricarda, Pérez Persona, Ernesto, Arnao, Mario, García-Guiñón, Antoni, Domingo, Abel, González-Pardo, Miriam, de la Rubia, Javier, Mateos, María Victoria

المصدر: Hematology; Dec2023, Vol. 28 Issue 1, p1-11, 11p

مصطلحات موضوعية: MULTIPLE myeloma, MONOCLONAL antibodies, CLINICAL trials, PROGRESSION-free survival

مستخلص: To describe the incorporation of monoclonal antibodies (mAb) in real-world (RW) practice for the treatment of patients with relapsed refractory multiple myeloma (RRMM) in a setting with other treatment alternatives. This was an observational, multicenter, ambispective study of RRMM treated with or without a mAb. A total of 171 patients were included. For the group treated without mAb, the median (95% CI) progression-free survival (PFS) to relapse was 22.4 (17.8-27.0) months; partial response or better (≥PR) and complete response or better (≥CR) was observed in 74.1% and 24.1% of patients, respectively; and median time to first response in first relapse was 2.0 months and in second relapse was 2.5 months. For the group of patients treated with mAb in first or second relapse, the median PFS was 20.9 (95% CI, could not be evaluated) months; the ≥ PR and ≥ CR rates were 76,2% and 28.6%, respectively; and the median time to first response in first relapse was 1.2 month and in second relapse was 1.0 months. The safety profiles for the combinations were consistent with those expected. The incorporation of mAb in RW practice for the treatment of RRMM has shown good quality and speed of response with a similar safety profile shown in randomized clinical trials. [ABSTRACT FROM AUTHOR]

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المؤلفون: Paiva, Bruno, Puig, Noemi, Cedena, Maria-Teresa, Rosiñol, Laura, Cordón, Lourdes, Vidriales, María-Belén, Burgos, Leire, Flores-Montero, Juan, Sanoja-Flores, Luzalba, Lopez-Anglada, Lucia, Maldonado, Roberto, de la Cruz, Javier, Gutierrez, Norma C, Calasanz, Maria-Jose, Martin-Ramos, Maria-Luisa, Garcia-Sanz, Ramón, Martinez-Lopez, Joaquin, Oriol, Albert, Blanchard, María-Jesús, Rios, Rafael, Martin, Jesus, Martinez-Martinez, Rafael, Sureda, Anna, Hernandez, Miguel-Teodoro, de la Rubia, Javier, Krsnik, Isabel, Moraleda, Jose-Maria, Palomera, Luis, Bargay, Joan, Van Dongen, Jacques J M, Orfao, Alberto, Mateos, Maria-Victoria, Blade, Joan, San-Miguel, Jesús F, Lahuerta, Juan-José, GEM (Grupo Español de Mieloma)/PETHEMA (Programa Para el Estudio de la Terapéutica en Hemopatías Malignas) Cooperative Study Group

مصطلحات موضوعية: Antineoplastic Combined Chemotherapy Protocols, Bortezomib, Clinical Trials, Phase III as Topic, Dexamethasone, Female, Flow Cytometry, Humans, Lenalidomide, Longitudinal Studies, Male, Middle Aged, Multiple Myeloma, Neoplasm, Residual, Randomized Controlled Trials as Topic

الوصف: Assessing measurable residual disease (MRD) has become standard with many tumors, but the clinical meaning of MRD in multiple myeloma (MM) remains uncertain, particularly when assessed by next-generation flow (NGF) cytometry. Thus, we aimed to determine the applicability and sensitivity of the flow MRD-negative criterion defined by the International Myeloma Working Group (IMWG). In the PETHEMA/GEM2012MENOS65 trial, 458 patients with newly diagnosed MM had longitudinal assessment of MRD after six induction cycles with bortezomib, lenalidomide, and dexamethasone (VRD), autologous transplantation, and two consolidation courses with VRD. MRD was assessed in 1,100 bone marrow samples from 397 patients; the 61 patients without MRD data discontinued treatment during induction and were considered MRD positive for intent-to-treat analysis. The median limit of detection achieved by NGF was 2.9 × 10-6. Patients received maintenance (lenalidomide ± ixazomib) according to the companion PETHEMA/GEM2014MAIN trial. Overall, 205 (45%) of 458 patients had undetectable MRD after consolidation, and only 14 of them (7%) have experienced progression thus far; seven of these 14 displayed extraosseous plasmacytomas at diagnosis and/or relapse. Using time-dependent analysis, patients with undetectable MRD had an 82% reduction in the risk of progression or death (hazard ratio, 0.18; 95% CI, 0.11 to 0.30; P The IMWG flow MRD-negative response criterion is highly applicable and sensitive to evaluate treatment efficacy in MM.

العلاقة: http://hdl.handle.net/10668/14743Test

الإتاحة: https://doi.org/10.1200/JCO.19.01231Test
http://hdl.handle.net/10668/14743Test

المؤلفون: de la Rubia, Javier^1,2 (AUTHOR) delarubia_jav@gva.es, Cejalvo, María J.¹ (AUTHOR), Ribas, Paz¹ (AUTHOR)

المصدر: Leukemia & Lymphoma. Feb2016, Vol. 57 Issue 2, p258-268. 11p.

مصطلحات موضوعية: *MULTIPLE myeloma diagnosis, *CANCER complications, *INFECTION risk factors, *IMMUNOMODULATORS, *CLINICAL trials

مستخلص: Infectious complications are an important risk factor for early mortality in patients with multiple myeloma. However, data about the impact and severity of infections in these patients in the era of new therapies have not been properly analyzed. This review has reviewed the incidence and severity of infections complications and infection-related mortality during induction treatment in patients with newly diagnosed myeloma receiving regimens with new drugs within randomized trials. The results show that infections are still a major cause of morbidity, especially among elderly patients receiving immunomodulatory drugs seen in up to 28% of patients in some trials vs less than 10% among transplant-eligible patients. Overall infection-related mortality ranged from 0–7% in transplant-ineligible patients, with no infection-related deaths in the majority of the trials including younger patients. Strategies directed to further reduce these complications and a better knowledge of their impact in patients treated outside clinical trials are needed. [ABSTRACT FROM PUBLISHER]

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

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

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

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

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

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

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

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

: Copyright of Cancers is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Mateos, María-Victoria¹ mvmateos@usal.es, Hernández, Miguel-Teodoro², Giraldo, Pilar³, de la Rubia, Javier⁴, de Arriba, Felipe⁵, Corral, Lucía López¹, Rosiñol, Laura⁶, Paiva, Bruno⁷, Palomera, Luis⁸, Bargay, Joan⁹, Oriol, Albert¹⁰, Prosper, Felipe⁷, López, Javier¹¹, Arguiñano, José-María¹², Quintana, Nuria¹³, García, José-Luis¹³, Bladé, Joan⁶, Lahuerta, Juan-José¹⁴, Miguel, Jesús-F San⁷

المصدر: Lancet Oncology. Aug2016, Vol. 17 Issue 8, p1127-1136. 10p.

مصطلحات موضوعية: *MULTIPLE myeloma treatment, *DEXAMETHASONE, *MULTIPLE myeloma, *MEDICAL protocols, *CLINICAL trials, *DISEASE risk factors, *ANTINEOPLASTIC agents, *COMPARATIVE studies, *LONGITUDINAL method, *RESEARCH methodology, *MEDICAL cooperation, *PROGNOSIS, *RESEARCH, *SURVIVAL, *THALIDOMIDE, *TUMOR classification, *EVALUATION research, *RANDOMIZED controlled trials, *CASE-control method

مستخلص: Background: The standard of care for smouldering multiple myeloma is observation. We did the QuiRedex study to compare early treatment with lenalidomide plus dexamethasone with observation in patients with high-risk smouldering multiple myeloma. Here we report the long-term follow-up results of the trial.Methods: We did this open-label, randomised, controlled phase 3 study at 19 centres in Spain and three centres in Portugal. Patients aged 18 years or older with high-risk smouldering multiple myeloma were randomly assigned (1:1), via a computerised random number generator, to receive either early treatment with lenalidomide plus dexamethasone or observation, with dynamic balancing to maintain treatment balance within the two groups. Randomisation was stratified by time from diagnosis of smouldering multiple myeloma to study enrolment (≤6 months vs >6 months). Patients in the treatment group received nine 4-week induction cycles (lenalidomide 25 mg per day on days 1-21, plus dexamethasone 20 mg per day on days-1-4 and days 12-15), followed by maintenance therapy (lenalidomide 10 mg per day on days 1-21 of each 28-day cycle) up to 2 years. Group allocation was not masked from study investigators or patients. The primary endpoint was time from randomisation to progression to symptomatic myeloma. The primary analysis was based on the per-protocol population, restricted to patients who fulfilled the protocol in terms of eligibility. Safety assessments were based on the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT00480363.Findings: Between Nov 8, 2007, and June 9, 2010, 125 patients were enrolled and underwent randomisation. 119 patients comprised the per-protocol population and were randomly assigned to receive either lenalidomide plus dexamethasone (n=57) or observation (n=62). The cutoff date for this update was June 30, 2015. Median follow-up for surviving patients was 75 months (IQR 67-85). Lenalidomide plus dexamethasone continued to provide a benefit on time to progression compared with observation (median time to progression not reached [95% CI 47 months-not reached] vs 23 months [16-31]; hazard ratio [HR] 0·24 [95% CI 0·14-0·41]; p<0·0001). Progression to multiple myeloma occurred in 53 (86%) of 62 patients in the observation group compared with 22 (39%) of 57 patients in the treatment group. At data cutoff, ten (18%) patients had died in the treatment group and 22 (36%) patients had died in the observation group; median overall survival from the time of study entry had not been reached in either group (95% CI 65 months-not reached vs 53 months-not reached; HR 0·43 [95% CI 0·21-0·92], p=0·024). Survival in patients who had received subsequent treatments at the time of progression to active disease did not differ between groups (HR 1·34 [95% CI 0·54-3·30]; p=0·50). The most frequently reported grade 3 adverse events in patients given lenalidomide plus dexamethasone were infection (four [6%]), asthenia (four [6%]), neutropenia (three [5%]), and skin rash (two [3%]); these events all occurred during induction therapy. No grade 4 adverse events occurred, but one (2%) patient in the lenalidomide plus dexamethasone group died from a respiratory infection during induction therapy The frequency of second primary malignancies was higher in patients in the treatment group than in those in the observation group (six [10%] of 62 patients vs one [2%] of 63 patients), but the cumulative risk of development did not differ significantly between the groups (p=0·070).Interpretation: This study is, to our knowledge, the first randomised trial in which early treatment has been assessed in selected patients with high-risk smouldering multiple myeloma. Positive results from ongoing trials would support the use of early treatment for patients with high-risk disease in the near future.Funding: Pethema (Spanish Program for the Treatment of Hematologic Diseases). [ABSTRACT FROM AUTHOR]