78 results on '"Roberto Mina"'
Search Results
2. P804: PLASMA CELL LEUKEMIA-LIKE TRANSCRIPTOME OF BONE MARROW PLASMA CELLS AND CIRCULATING TUMOR CELL LEVELS IN PERIPHERAL BLOOD COMPLEMENTARILY DEFINE HIGH-RISK IN NEWLY DIAGNOSED MULTIPLE MYELOMA
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Mattia D’agostino, Davine Hofste Op Bruinink, Mark van Duin, Delia Rota-Scalabrini, Luca Bertamini, Rowan Kuiper, Angelo Belotti, Vincenzo Marasco, Stefania Oliva, Elena Rivolti, Jennifer Rogers, Roberto Mina, Mariella Grasso, Antonio Ledda, Massimo Offidani, Monica Galli, Michele Cavo, Annemiek Broijl, Pellegrino Musto, Benedetto Bruno, Mario Boccadoro, Pieter Sonneveld, and Francesca Gay
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2023
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3. P895: DARATUMUMAB PLUS POMALIDOMIDE AND DEXAMETHASONE (DPD) IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA AND 17P DELETION: UPDATED ANALYSIS OF THE DEDALO PHASE II TRIAL
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Vittorio Montefusco, Anna Maria Cafro, Gloria Margiotta-Casaluci, Francesca Patriarca, Roberto Mina, Mattia D’agostino, Anna Benedetta Dalla Palma, Rita Rizzi, Angelo Genua, Francesca Fazio, Laura Paris, Angelo Belotti, Ilaria Rizzello, Concetta Conticello, Carmelo Carlo-Stella, and Mario Boccadoro
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2023
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4. P872: EFFICACY OF DARATUMUMAB PLUS BORTEZOMIB, CYCLOPHOSPHAMIDE AND DEXAMETHASONE IN PATIENTS WITH MULTIPLE MYELOMA PRESENTING WITH EXTRAMEDULLARY DISEASE: A EUROPEAN MYELOMA NETWORK STUDY (EMN19)
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Meral Beksac, Tulin Tuglular, Francesca Gay, Roberto Mina, Eirini Katodritou, Ali Unal, Michele Cavo, Guner Hayri Ozsan, Vincent H.J. van der Velden, Berna Beverloo, Michael Vermeulen, Mark van Duin, Guldane Cengiz, Omur Gokmen Sevindik, Serena Merante, Kyriaki Manousou, Pieter Sonneveld, and Evangelos Terpos
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2023
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5. Elotuzumab plus pomalidomide and dexamethasone in relapsed/refractory multiple myeloma: a multicenter, retrospective, real-world experience with 200 cases outside of controlled clinical trials
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Massimo Gentile, Ernesto Vigna, Salvatore Palmieri, Monica Galli, Daniele Derudas, Roberto Mina, Roberta Della Pepa, Renato Zambello, Enrica Antonia Martino, Antonella Bruzzese, Silvia Mangiacavalli, Elena Zamagni, Catello Califano, Maurizio Musso, Concetta Conticello, Claudio Cerchione, Giuseppe Mele, Nicola Di Renzo, Massimo Offidani, Giuseppe Tarantini, Gloria Margiotta Casaluci, Angela Rago, Roberto Ria, Giuseppina Uccello, Gregorio Barilà, Gaetano Palumbo, Alessandra Pompa, Donatella Vincelli, Marino Brunori, Fabrizio Accardi, Valeria Amico, Angela Amendola, Raffaele Fontana, Velia Bongarzoni, Bernardo Rossini, Emilia Cotzia, Alessandro Gozzetti, Rita Rizzi, Nicola Sgherza, Eleonora Ferretti, Giuseppe Bertuglia, Davide Nappi, Maria Teresa Petrucci, Francesco Di Raimondo, Antonino Neri, Fortunato Morabito, and Pellegrino Musto
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
In the ELOQUENT-3 trial, the combination of elotuzumab, pomalidomide and dexamethasone (EloPd) proved to have a superior clinical benefit over pomalidomide and dexamethasone with a manageable toxicity profile, leading to its approval for the treatment of patients with relapsed/refractory multiple myeloma (RRMM) who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor. We report here a real-world experience of 200 cases of RRMM treated with EloPd in 35 Italian centers outside of clinical trials. In our dataset, the median number of prior lines of therapy was two, with 51% of cases undergoing autologous stem cell transplant and 73% having been exposed to daratumumab. After a median follow-up of 9 months, 126 patients had stopped EloPd, most of them (88.9%) because of disease progression. The overall response rate was 55.4%, a finding in line with the pivotal trial results. Regarding adverse events, the toxicity profile in our cohort was similar to that in the ELOQUENT-3 trial, with no significant differences between younger (
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- 2023
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6. Ixazomib-based induction regimens plus ixazomib maintenance in transplant-ineligible, newly diagnosed multiple myeloma: the phase II, multi-arm, randomized UNITO-EMN10 trial
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Roberto Mina, Antonietta Pia Falcone, Sara Bringhen, Anna Marina Liberati, Norbert Pescosta, Maria Teresa Petrucci, Giovannino Ciccone, Andrea Capra, Francesca Patriarca, Delia Rota-Scalabrini, Francesca Bonello, Caterina Musolino, Michele Cea, Renato Zambello, Paola Tacchetti, Angelo Belotti, Claudia Cellini, Laura Paris, Mariella Grasso, Sara Aquino, Lorenzo De Paoli, Giovanni De Sabbata, Stelvio Ballanti, Massimo Offidani, Mario Boccadoro, Federico Monaco, Paolo Corradini, and Alessandra Larocca
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2021
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7. Lenalidomide-based triplet regimens in first relapsed multiple myeloma patients: real-world evidence from a propensity score matched analysis
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Silvia Mangiacavalli, Claudio Salvatore Cartia, Monica Galli, Sara Pezzatti, Angelo Belotti, Francesca Fazio, Roberto Mina, Magda Marcatti, Anna Cafro, Renato Zambello, Laura Paris, Gregorio Barilà, Cecilia Olivares, Alessandra Pompa, Rita Mazza, Francesca Farina, Martina Soldarini, Pietro Benvenuti, Giuseppina Pagani, Michele Palumbo, Valeria Masoni, Virginia Valeria Ferretti, Catherine Klersy, Luca Arcaini, and Maria Teresa Petrucci
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Lenalidomide and dexamethasone (Rd)-based triplets, in particular carfilzomib-Rd (KRd) and daratumumab-Rd (DaraRd), represent a standard of care in lenalidomide-sensitive multiple myeloma (MM) patients in first relapse. Meta-analysis of randomized clinical trials (RCT), suggested better outcome with DaraRd. Trying to address this issue in clinical practice, we collected data of 430 consecutive MM patients addressed to Rd-based triplets in first relapse between January 2017 and March 2021. Overall, the most common used regimen was DaraRd, chosen in almost half of the cases (54.4%), followed by KRd (34.6%). Different triplets were used much less commonly. In an attempt to limit the imbalance of a retrospective analysis, we conducted a propensity score matching (PSM) comparison between DaraRd and KRd. After PSM, efficacy of DaraRd versus KRd was similar in terms of overall-response rate (ORR) (OR: 0.9, P=0.685) as well as of very good partial response (VGPR) or better (OR: 0.9, P=0.582). The median progression-free survival (PFS) was significantly longer for DaraRd (29.8 vs. 22.5 months; P=0.028). DaraRd was tolerated better, registering a lower rate of grade 3-4 non-hematological toxicity (OR: 0.4, P
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- 2022
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8. Safety of Rapid Daratumumab Infusion: A Retrospective, Multicenter, Real-Life Analysis on 134 Patients With Multiple Myeloma
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Francesca Bonello, Serena Rocchi, Gregorio Barilà, Michela Sandrone, Marco Talarico, Elena Zamagni, Matilde Scaldaferri, Susanna Vedovato, Cecilia Bertiond, Laura Pavan, Sara Bringhen, Francesco Cattel, Renato Zambello, Michele Cavo, and Roberto Mina
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multiple myeloma ,daratumumab ,rapid infusion ,real life ,infusion-related reactions ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
BackgroundThe anti-CD38 monoclonal antibody daratumumab is the backbone of most anti-multiple myeloma (MM) regimens. To mitigate the risk of infusion-related reactions (IRRs), intravenous daratumumab administration requires 7 hours for the first infusion and 3.5-4 hours thereafter, thus making daratumumab-containing regimens burdensome for patients and health care resources. Preliminary data suggest that a rapid (90-minute) infusion of daratumumab is safe and does not increase IRRs. The rapid schedule was adopted by our centers since 2019.MethodsWe conducted an observational multi-center, real-life study to assess the safety of rapid daratumumab infusion protocol from the third administration in relapsed MM patients receiving daratumumab alone or in combination with lenalidomide-dexamethasone or bortezomib-dexamethasone. The primary endpoint was the safety of the rapid infusion protocol, particularly in terms of IRRs.ResultsA total of 134 MM patients were enrolled. IRRs occurred in 7 (5%) patients and were mostly mild (6/7 of grade 1-2), with only 1 patient experiencing a grade 3 IRR. Due to the IRRs, 5 (3.7%) patients discontinued the rapid infusions and resumed daratumumab at the standard infusion rate, while 1 patient permanently discontinued daratumumab. In 4/7 patients (57%), IRRs occurred while resuming rapid daratumumab infusions after a temporary interruption (2-4 months). No other adverse event was considered related to the rapid infusion protocol.ConclusionsOur findings confirmed the safety of rapid daratumumab infusions starting from the third administration. In case of prolonged daratumumab interruption, it is advisable to resume infusions at the standard rate (3.5 hours) before switching to the rapid infusion.
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- 2022
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9. Ultra-Low-Dose Whole-Body Computed Tomography Protocol Optimization for Patients With Plasma Cell Disorders: Diagnostic Accuracy and Effective Dose Analysis From a Reference Center
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Davide Tore, Osvaldo Rampado, Carla Guarnaccia, Roberto Mina, Maria Oronzio, Ambra Santonocito, Alessandro Serafini, Giulio Antonino Strazzarino, Laura Gianusso, Sara Bringhen, Paolo Fonio, and Alessandro Depaoli
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ultra-low-dose whole-body CT ,multiple myeloma ,plasma cell disorders ,effective dose ,dose reduction ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
BackgroundThe whole-body low-dose CT (WBLDCT) is the first-choice imaging technique in patients with suspected plasma cell disorder to assess the presence of osteolytic lesions. We investigated the performances of an optimized protocol, evaluating diagnostic accuracy and effective patient dose reduction using a latest generation scanner.Methods and MaterialsRetrospective study on 212 patients with plasma cell disorders performed on a 256-row CT scanner. First, WBLDCT examinations were performed using a reference protocol with acquisition parameters obtained from literature. A phantom study was performed for protocol optimization for subsequent exams to minimize dose while maintaining optimal diagnostic accuracy. Images were analyzed by three readers to evaluate image quality and to detect lesions. Effective doses (E) were evaluated for each patient considering the patient dimensions and the tube current modulation.ResultsA similar, very good image quality was observed for both protocols by all readers with a good agreement at repeated measures ANOVA test (p>0.05). An excellent inter-rater agreement for lesion detection was achieved obtaining high values of Fleiss’ kappa for all the districts considered (p
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- 2021
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10. Advances and Hurdles in CAR T Cell Immune Therapy for Solid Tumors
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Francesco Boccalatte, Roberto Mina, Andrea Aroldi, Sarah Leone, Carter M. Suryadevara, Dimitris G. Placantonakis, and Benedetto Bruno
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solid tumors ,chimeric antigen receptor (CAR) T cell ,adoptive immunotherapy ,receptors ,chimeric antigen ,tumor microenvironment ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Chimeric antigen receptor (CAR) T cells in solid tumors have so far yielded limited results, in terms of therapeutic effects, as compared to the dramatic results observed for hematological malignancies. Many factors involve both the tumor cells and the microenvironment. The lack of specific target antigens and severe, potentially fatal, toxicities caused by on-target off-tumor toxicities constitute major hurdles. Furthermore, the tumor microenvironment is usually characterized by chronic inflammation, the presence of immunosuppressive molecules, and immune cells that can reduce CAR T cell efficacy and facilitate antigen escape. Nonetheless, solid tumors are under investigation as possible targets despite their complexity, which represents a significant challenge. In preclinical mouse models, CAR T cells are able to efficiently recognize and kill several tumor xenografts. Overall, in the next few years, there will be intensive research into optimizing novel cell therapies to improve their effector functions and keep untoward effects in check. In this review, we provide an update on the state-of-the-art CAR T cell therapies in solid tumors, focusing on the preclinical studies and preliminary clinical findings aimed at developing optimal strategies to reduce toxicity and improve efficacy.
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- 2022
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11. First-line therapy with either bortezomib-melphalan-prednisone or lenalidomide-dexamethasone followed by lenalidomide for transplant-ineligible multiple myeloma patients: a pooled analysis of two randomized trials
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Alessandra Larocca, Roberto Mina, Massimo Offidani, Anna Marina Liberati, Antonio Ledda, Francesca Patriarca, Andrea Evangelista, Stefano Spada, Giulia Benevolo, Daniela Oddolo, Vanessa Innao, Clotilde Cangiolosi, Annalisa Bernardini, Pellegrino Musto, Valeria Amico, Vincenzo Fraticelli, Laura Paris, Nicola Giuliani, Antonietta Pia Falcone, Renato Zambello, Lorenzo De Paoli, Alessandra Romano, Antonio Palumbo, Vittorio Montefusco, Roman Hájek, Mario Boccadoro, and Sara Bringhen
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Bortezomib-melphalan-prednisone (VMP) and continuous lenalidomide-dexamethasone (Rd) represent the standard treatment of transplant-ineligible patients with newly diagnosed multiple myeloma (MM). To date, no randomized trial has compared VMP to Rd, and there is no evidence of the optimal treatment for newly diagnosed MM, particularly in patients with high-risk cytogenetics [del(17p), t(4;14) or t(14;16)]. We pooled together data from patients with newly diagnosed MM treated with VMP or Rd induction followed by lenalidomide maintenance 10 mg (Rd-R) enrolled in the GIMEMA-MM-03-05 and EMN01 trials, to evaluate the efficacy of these treatments in different subgroups of patients, focusing on those with standard- and high-risk cytogenetics. Overall, 474 patients were analyzed (VMP: 257 patients; Rd-R: 217 patients). No differences in progression-free survival (hazard ratio=0.96) and overall survival (hazard ratio=1.08) were observed between standard-risk patients treated with VMP or Rd-R, whereas among the high-risk patients, the probabilities of progression (hazard ratio=0.54) and death (hazard ratio=0.73) were lower in the patients treated with VMP than in those treated with Rd-R. In particular, standard-risk patients >75 years benefited less from VMP than from Rd-R (hazard ratio for progression-free survival=0.96; hazard ratio for overall survival=1.81). In this non-randomized analysis, VMP and Rd-R were equally effective in younger (≤75 years), standard-risk patients, while older ones (>75 years) benefited more from Rd-R. In high-risk patients, VMP improved progression-free survival and overall survival irrespective of age. The source trials are registered at ClinicalTrials.gov (NCT01063179 and NCT01093196).
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- 2020
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12. Carfilzomib, cyclophosphamide and dexamethasone for newly diagnosed, high-risk myeloma patients not eligible for transplant: a pooled analysis of two studies
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Roberto Mina, Francesca Bonello, Maria Teresa Petrucci, Anna Marina Liberati, Concetta Conticello, Stelvio Ballanti, Pellegrino Musto, Attilio Olivieri, Giulia Benevolo, Andrea Capra, Milena Gilestro, Piero Galieni, Michele Cavo, Agostina Siniscalchi, Antonio Palumbo, Vittorio Montefusco, Gianluca Gaidano, Paola Omedé, Mario Boccadoro, and Sara Bringhen
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Despite remarkable advances in the treatment of multiple myeloma in the last decades, the prognosis of patients harboring high-risk cytogenetic abnormalities remains dismal as compared to that of standard-risk patients. Proteasome inhibitors demonstrated to partially ameliorate the prognosis of high-risk patients. We pooled together data from two phase I/II trials on transplant-ineligible patients with multiple myeloma receiving upfront carfilzomib cyclophosphamide and dexamethasone followed by carfilzomib maintenance. The aim of this analysis was to compare treatment outcomes in patients with standard- versus high-risk cytogenetic abnormalities detected by fluorescence in situ hybridization (FISH) analysis. High risk was defined by the presence of at least one chromosomal abnormality, including t(4;14), del17p and t(14;16). Overall, 94 patients were included in the analysis: 57 (61%) in the standard-risk and 37 (39%) in the high-risk group. Median follow-up was 38 months. In standard- vs. high-risk patients, we observed similar progression-free survival (3-year PFS: 52% vs. 43%, respectively; p=0.50), overall survival (3-year OS: 78% vs. 73%; p=0.38), and overall response rate (88% vs 95%; p=0.47), with no statistical differences between the two groups. No difference in terms of progression-free survival was observed between patients with or without del17p. Carfilzomib, used both as induction and maintenance agent for transplant-ineligible newly diagnosed multiple myeloma patients, mitigated the poor prognosis carried by high-risk cytogenetics and resulted into similar progression-free survival and overall survival, as compared to standard-risk patients. ClinicalTrials.gov IDs: NCT01857115 (IST-CAR-561) and NCT01346787 (IST-CAR-506).
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- 2020
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13. Once-weekly versus twice-weekly carfilzomib in patients with newly diagnosed multiple myeloma: a pooled analysis of two phase I/II studies
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Sara Bringhen, Roberto Mina, Maria Teresa Petrucci, Gianluca Gaidano, Stelvio Ballanti, Pellegrino Musto, Massimo Offidani, Stefano Spada, Giulia Benevolo, Elena Ponticelli, Piero Galieni, Michele Cavo, Tommaso Caravita Di Toritto, Francesco Di Raimondo, Vittorio Montefusco, Antonio Palumbo, Mario Boccadoro, and Alessandra Larocca
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Twice-weekly carfilzomib is approved at 27 and 56 mg/m2 to treat relapsed multiple myeloma patients. In the phase III study ARROW, once-weekly 70 mg/m 2 carfilzomib prolonged the median progression-free survival of relapsed multiple myeloma patients in comparison with twice-weekly 27 mg/m2 carfilzomib, without adding significant toxicity. Data were pooled from two phase I/II studies of newly diagnosed multiple myeloma patients who received nine induction cycles of carfilzomib (either 70 mg/m2 once-weekly or 36 mg/m2 twice-weekly), cyclophosphamide and dexamethasone, followed by carfilzomib maintenance. Overall, 121 transplant-ineligible patients with newly diagnosed multiple myeloma were analyzed (once-weekly, n=63; twice-weekly, n=58). We found no significant difference in median progression-free survival [35.7 months (95%CI: 23.7-not reached, NR) vs. 35.5 months (95%CI: 24.3-NR); HR: 1.39; P=0.26] and 3-year overall survival [70% [95%CI: 59%-84%) vs. 72% (95%CI: 60%-85%); HR: 1.27; P=0.5] between once-weekly and twice-weekly carfilzomib. From the start of maintenance, 3-year progression-free survival [47% (95%CI: 33%-68%) vs. 51% (95%CI: 38%-70%); HR: 1.04; P=0.92] and overall survival [72% (95%CI: 58%-89%) vs. 73% (95%CI: 59%-90%); HR: 0.82; P=0.71] were similar in the once- versus twice-weekly carfilzomib. The rate of grade 3-5 hematologic (24% vs. 30%; P=0.82) and non-hematologic (38% vs. 41%; P=0.83) adverse events was similar in the two groups. Once-weekly 70 mg/m2 carfilzomib as induction and maintenance therapy for newly diagnosed multiple myeloma patients was as safe and effective as twice-weekly 36 mg/m2 carfilzomib and provided a more convenient schedule. The trials are registered at clinicaltrials.gov identifiers: 01857115 (IST-CAR-561) and 01346787 (IST-CAR-506).
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- 2019
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14. Erratum: Mina, R.; et al. Minimal Residual Disease in Multiple Myeloma: State of the Art and Future Perspectives. J. Clin. Med. 2020, 9, 2142
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Roberto Mina, Stefania Oliva, and Mario Boccadoro
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n/a ,Medicine - Abstract
The authors sincerely apologize for the inaccuracies made during the revision that a product line has been associated with the wrong company [...]
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- 2020
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15. Minimal Residual Disease in Multiple Myeloma: State of the Art and Future Perspectives
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Roberto Mina, Stefania Oliva, and Mario Boccadoro
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multiple myeloma ,minimal residual disease ,next-generation sequencing ,next-generation flow ,Medicine - Abstract
Minimal residual disease (MRD) detection represents a sensitive tool to appropriately measure the response obtained with therapies for multiple myeloma (MM). The achievement of MRD negativity has superseded the conventional complete response (CR) and has been proposed as a surrogate endpoint for progression-free survival and overall survival. Several techniques are available for the detection of MRD inside (next-generation sequencing, flow cytometry) and outside (PET/CT, magnetic resonance) the bone marrow, and their complementary use allows a precise definition of the efficacy of anti-myeloma treatments. This review summarizes MRD data and results from previous clinical trials, highlights open issues related to the role of MRD in MM and discusses how MRD could be implemented in clinical practice to inform on patient prognosis and drive therapeutic decisions.
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- 2020
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16. Prevention and management of adverse events during treatment with bispecific antibodies and CAR T cells in multiple myeloma:a consensus report of the European Myeloma Network
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Heinz Ludwig, Evangelos Terpos, Niels van de Donk, Maria-Victoria Mateos, Philippe Moreau, Melitios-Athanasios Dimopoulos, Michel Delforge, Paula Rodriguez-Otero, Jesús San-Miguel, Kwee Yong, Francesca Gay, Hermann Einsele, Roberto Mina, Jo Caers, Christoph Driessen, Pellegrino Musto, Sonja Zweegman, Monika Engelhardt, Gordon Cook, Katja Weisel, Annemiek Broijl, Meral Beksac, Jelena Bila, Fredrik Schjesvold, Michele Cavo, Roman Hajek, Cyrille Touzeau, Mario Boccadoro, and Pieter Sonneveld
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Oncology - Abstract
T-cell redirecting bispecific antibodies (BsAbs) and chimeric antigen receptor T cells (CAR T cells) have revolutionised multiple myeloma therapy, but adverse events such as cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome (ICANS), cytopenias, hypogammaglobulinaemia, and infections are common. This Policy Review presents a consensus from the European Myeloma Network on the prevention and management of these adverse events. Recommended measures include premedication, frequent assessing for symptoms and severity of cytokine release syndrome, step-up dosing for several BsAbs and some CAR T-cell therapies; corticosteroids; and tocilizumab in the case of cytokine release syndrome. Other anti-IL-6 drugs, high-dose corticosteroids, and anakinra might be considered in refractory cases. ICANS often arises concomitantly with cytokine release syndrome. Glucocorticosteroids in increasing doses are recommended if needed, as well as anakinra if the response is inadequate, and anticonvulsants if convulsions occur. Preventive measures against infections include antiviral and antibacterial drugs and administration of immunoglobulins. Treatment of infections and other complications is also addressed.
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- 2023
17. Dedalo: Phase II Study of Daratumumab Plus Pomalidomide and Dexamethasone (DPd) in Patients with Relapsed/Refractory Multiple Myeloma and 17p Deletion
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Vittorio Montefusco, Anna Maria Cafro, Gloria Margiotta Casaluci, Francesca Patriarca, Roberto Mina, Mattia D'Agostino, Andrea Capra, Claudia Priola, Anna Benedetta Dalla Palma, Rita Rizzi, Angelo Genua, Maria Teresa Petrucci, Laura Paris, Angelo Belotti, Michele Cavo, Concetta Conticello, Carmelo Carlo-Stella, and Mario Boccadoro
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
18. DVRd Followed By Ciltacabtagene Autoleucel Versus DVRd Followed By ASCT in Patients with Newly Diagnosed Multiple Myeloma Who Are Transplant Eligible: A Randomized Phase 3 Study (EMagine/CARTITUDE-6)
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Mario Boccadoro, Jesús San-Miguel, Kenshi Suzuki, Niels W.C.J. Van De Donk, Gordon Cook, Andrzej Jakubowiak, Deepu Madduri, Salma Afifi, An-Sofie Stevens, Jordan M. Schecter, William Deraedt, Steven Kuppens, Pankaj Mistry, Lida Pacaud, Erika Florendo, Annemiek Broijl, Francesca Gay, Roberto Mina, Leo Rasche, Philippe Moreau, María-Victoria Mateos, Hermann Einsele, and Pieter Sonneveld
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
19. Supplementary Figure S5 from Development and Validation of a Simplified Score to Predict Early Relapse in Newly Diagnosed Multiple Myeloma in a Pooled Dataset of 2,190 Patients
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Francesca Gay, Mario Boccadoro, Pellegrino Musto, Pieter Sonneveld, Andrew Spencer, Roman Hájek, Arnon Nagler, Gianluca Gaidano, Angelo Belotti, Giulia Benevolo, Francesca Patriarca, Roberto Mina, Marina Ruggeri, Nicola Cascavilla, Paolo de Fabritiis, Donato Mannina, Anna Marina Liberati, Alessandra Romano, Andrea Capra, Paolo Corradini, Massimo Offidani, Maria Teresa Petrucci, Luca Bertamini, and Gian Maria Zaccaria
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Figure S5. OS from relapse (A) and 2nd PFS (B) in patients with ER18 vs. late relapse (LR)
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- 2023
20. Supplementary Appendix from Development and Validation of a Simplified Score to Predict Early Relapse in Newly Diagnosed Multiple Myeloma in a Pooled Dataset of 2,190 Patients
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Francesca Gay, Mario Boccadoro, Pellegrino Musto, Pieter Sonneveld, Andrew Spencer, Roman Hájek, Arnon Nagler, Gianluca Gaidano, Angelo Belotti, Giulia Benevolo, Francesca Patriarca, Roberto Mina, Marina Ruggeri, Nicola Cascavilla, Paolo de Fabritiis, Donato Mannina, Anna Marina Liberati, Alessandra Romano, Andrea Capra, Paolo Corradini, Massimo Offidani, Maria Teresa Petrucci, Luca Bertamini, and Gian Maria Zaccaria
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Supplementary Appendix: • SUPPLEMENTARY METHODS. iFISH; ER24 analysis; clinical endpoints; statistical analysis; • SUPPLEMENTARY RESULTS. ER24 analysis; DS-ERMM score - additional analyses; outcome after relapse in the ER18 analysis; • TABLE S1A. Treatment regimens in the source studies; • TABLE S1B. Eligibility criteria for clinical trials; • TABLE S2. Patient characteristics in the overall population and stratified according to the ER24 outcome as training set and validation set; • TABLE S3. Univariate (UV) and multivariate (MV) analyses of the baseline features to predict ER24; LIST OF SUPPLEMENTARY FIGURE FILES.
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- 2023
21. Data from Development and Validation of a Simplified Score to Predict Early Relapse in Newly Diagnosed Multiple Myeloma in a Pooled Dataset of 2,190 Patients
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Francesca Gay, Mario Boccadoro, Pellegrino Musto, Pieter Sonneveld, Andrew Spencer, Roman Hájek, Arnon Nagler, Gianluca Gaidano, Angelo Belotti, Giulia Benevolo, Francesca Patriarca, Roberto Mina, Marina Ruggeri, Nicola Cascavilla, Paolo de Fabritiis, Donato Mannina, Anna Marina Liberati, Alessandra Romano, Andrea Capra, Paolo Corradini, Massimo Offidani, Maria Teresa Petrucci, Luca Bertamini, and Gian Maria Zaccaria
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Purpose:Despite the improvement of therapeutic regimens, several patients with multiple myeloma (MM) still experience early relapse (ER). This subset of patients currently represents an unmet medical need.Experimental Design:We pooled data from seven European multicenter phase II/III clinical trials enrolling 2,190 patients with newly diagnosed MM from 2003 to 2017. Baseline patient evaluation included 14 clinically relevant features. Patients with complete data (n = 1,218) were split into training (n = 844) and validation sets (n = 374). In the training set, a univariate analysis and a multivariate logistic regression model on ER within 18 months (ER18) were made. The most accurate model was selected on the validation set. We also developed a dynamic version of the score by including response to treatment.Results:The Simplified Early Relapse in Multiple Myeloma (S-ERMM) score was modeled on six features weighted by a score: 5 points for high lactate dehydrogenase or t(4;14); 3 for del17p, abnormal albumin, or bone marrow plasma cells >60%; and 2 for λ free light chain. The S-ERMM identified three patient groups with different risks of ER18: Intermediate (Int) versus Low (OR = 2.39, P < 0.001) and High versus Low (OR = 5.59, P < 0.001). S-ERMM High/Int patients had significantly shorter overall survival (High vs. Low: HR = 3.24, P < 0.001; Int vs. Low: HR = 1.86, P < 0.001) and progression-free survival-2 (High vs. Low: HR = 2.89, P < 0.001; Int vs. Low: HR = 1.76, P < 0.001) than S-ERMM Low. The Dynamic S-ERMM (DS-ERMM) modulated the prognostic power of the S-ERMM.Conclusions:On the basis of simple, widely available baseline features, the S-ERMM and DS-ERMM properly identified patients with different risks of ER and survival outcomes.
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- 2023
22. Melflufen or pomalidomide plus dexamethasone for patients with multiple myeloma refractory to lenalidomide (OCEAN): a randomised, head-to-head, open-label, phase 3 study
- Author
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Fredrik H Schjesvold, Meletios-Athanasios Dimopoulos, Sosana Delimpasi, Pawel Robak, Daniel Coriu, Wojciech Legiec, Luděk Pour, Ivan Špička, Tamas Masszi, Vadim Doronin, Jiri Minarik, Galina Salogub, Yulia Alekseeva, Antonio Lazzaro, Vladimir Maisnar, Gábor Mikala, Laura Rosiñol, Anna Marina Liberati, Argiris Symeonidis, Victoria Moody, Marcus Thuresson, Catriona Byrne, Johan Harmenberg, Nicolaas A Bakker, Roman Hájek, Maria-Victoria Mateos, Paul G Richardson, Pieter Sonneveld, Fredrik Schjesvold, Anna Nikolayeva, Waldemar Tomczak, Ludek Pour, Ivan Spicka, Gabor Mikala, Laura Rosinol, Tatiana Konstantinova, Anargyros Symeonidis, Moshe Gatt, Arpad Illes, Haifaa Abdulhaq, Moez Dungarwalla, Sebastian Grosicki, Roman Hajek, Xavier Leleu, Alexander Myasnikov, Paul G. Richardson, Irit Avivi, Dries Deeren, Mercedes Gironella, Miguel Teodoro Hernandez-Garcia, Joaquin Martinez Lopez, Muriel Newinger-Porte, Paz Ribas, Olga Samoilova, Eric Voog, Mario Arnao-Herraiz, Estrella Carrillo-Cruz, Paolo Corradini, Jyothi Dodlapati, Miquel Granell Gorrochategui, Shang-Yi Huang, Matthew Jenner, Lionel Karlin, Jin Seok Kim, Agnieszka Kopacz, Nadezhda Medvedeva, Chang-Ki Min, Roberto Mina, Katrin Palk, Ho-Jin Shin, Sang Kyun Sohn, Jason Tache, Achilles Anagnostopoulos, Jose-Maria Arguiñano, Michele Cavo, Joanne Filicko, Margaret Garnes, Janusz Halka, Kathrin Herzog-Tzarfati, Natalia Ipatova, Kihyun Kim, Maria-Theresa Krauth, Irina Kryuchkova, Mihaela Cornelia Lazaroiu, Mario Luppi, Andrei Proydakov, Alessandro Rambaldi, Milda Rudzianskiene, Su-Peng Yeh, Maria Magdalena Alcalá-Peña, Adrian Alegre Amor, Hussain Alizadeh, Maurizio Bendandi, Gillian Brearton, Randall Brown, Jim Cavet, Najib Dally, Miklos Egyed, José Ángel Hernández-Rivas, Ain Kaare, Jean-Michel Karsenti, Janusz Kloczko, William Kreisle, Je-Jung Lee, Sigrid Machherndl-Spandl, Sudhir Manda, Ivan Moiseev, Jan Moreb, Zsolt Nagy, Santosh Nair, Albert Oriol-Rocafiguera, Michael Osswald, Paula Otero-Rodriguez, Valdas Peceliunas, Torben Plesner, Philippe Rey, Giuseppe Rossi, Don Stevens, Celia Suriu, Corrado Tarella, Anke Verlinden, Alain Zannetti, Hematology, and Oncopeptides
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Published Online ,See Comment page e82 ,Malignancies ,University of ,Department of Hematology ,Hematology - Abstract
Background Melphalan flufenamide (melflufen), an alkylating peptide-drug conjugate, plus dexamethasone showed clinical activity and manageable safety in the phase 2 HORIZON study. We aimed to determine whether melflufen plus dexamethasone would provide a progression-free survival benefit compared with pomalidomide plus dexamethasone in patients with previously treated multiple myeloma. Methods In this randomised, open-label, head-to-head, phase 3 study (OCEAN), adult patients (aged ≥18 years) were recruited from 108 university hospitals, specialist hospitals, and community-based centres in 21 countries across Europe, North America, and Asia. Eligible patients had an ECOG performance status of 0–2; must have had relapsed or refractory multiple myeloma, refractory to lenalidomide (within 18 months of randomisation) and to the last line of therapy; and have received two to four previous lines of therapy (including lenalidomide and a proteasome inhibitor). Patients were randomly assigned (1:1), stratified by age, number of previous lines of therapy, and International Staging System score, to either 28-day cycles of melflufen and dexamethasone (melflufen group) or pomalidomide and dexamethasone (pomalidomide group). All patients received dexamethasone 40 mg orally on days 1, 8, 15, and 22 of each cycle. In the melflufen group, patients received melflufen 40 mg intravenously over 30 min on day 1 of each cycle and in the pomalidomide group, patients received pomalidomide 4 mg orally daily on days 1 to 21 of each cycle. The primary endpoint was progression-free survival assessed by an independent review committee in the intention-to-treat (ITT) population. Safety was assessed in patients who received at least one dose of study medication. This study is registered with ClinicalTrials.gov, NCT03151811, and is ongoing. Findings Between June 12, 2017, and Sept 3, 2020, 246 patients were randomly assigned to the melflufen group (median age 68 years [IQR 60–72]; 107 [43%] were female) and 249 to the pomalidomide group (median age 68 years [IQR 61–72]; 109 [44%] were female). 474 patients received at least one dose of study drug (melflufen group n=228; pomalidomide group n=246; safety population). Data cutoff was Feb 3, 2021. Median progression-free survival was 6·8 months (95% CI 5·0–8·5; 165 [67%] of 246 patients had an event) in the melflufen group and 4·9 months (4·2–5·7; 190 [76%] of 249 patients had an event) in the pomalidomide group (hazard ratio [HR] 0·79, [95% CI 0·64–0·98]; p=0·032), at a median follow-up of 15·5 months (IQR 9·4–22·8) in the melflufen group and 16·3 months (10·1–23·2) in the pomalidomide group. Median overall survival was 19·8 months (95% CI 15·1–25·6) at a median follow-up of 19·8 months (IQR 12·0–25·0) in the melflufen group and 25·0 months (95% CI 18·1–31·9) in the pomalidomide group at a median follow-up of 18·6 months (IQR 11·8–23·7; HR 1·10 [95% CI 0·85–1·44]; p=0·47). The most common grade 3 or 4 treatment-emergent adverse events were thrombocytopenia (143 [63%] of 228 in the melflufen group vs 26 [11%] of 246 in the pomalidomide group), neutropenia (123 [54%] vs 102 [41%]), and anaemia (97 [43%] vs 44 [18%]). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]). 27 [12%] patients in the melflufen group and 32 [13%] in the pomalidomide group had fatal treatment-emergent adverse events. Fatal treatment-emergent adverse events were considered possibly treatment related in two patients in the melflufen group (one with acute myeloid leukaemia, one with pancytopenia and acute cardiac failure) and four patients in the pomalidomide group (two patients with pneumonia, one with myelodysplastic syndromes, one with COVID-19 pneumonia). Interpretation Melflufen plus dexamethasone showed superior progression-free survival than pomalidomide plus dexamethasone in patients with relapsed or refractory multiple myeloma., Oncopeptides AB
- Published
- 2022
23. Lenalidomide-based triplet regimens in first relapsed multiple myeloma patients: real-world evidence from a propensity score matched analysis
- Author
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Silvia Mangiacavalli, Claudio Salvatore Cartia, Monica Galli, Sara Pezzatti, Angelo Belotti, Francesca Fazio, Roberto Mina, Magda Marcatti, Anna Cafro, Renato Zambello, Laura Paris, Gregorio Barilà, Cecilia Olivares, Alessandra Pompa, Rita Mazza, Francesca Farina, Martina Soldarini, Pietro Benvenuti, Giuseppina Pagani, Michele Palumbo, Valeria Masoni, Virginia Valeria Ferretti, Catherine Klersy, Luca Arcaini, and Maria Teresa Petrucci
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Hematology - Abstract
Lenalidomide and dexamethasone (Rd)-based triplets, in particular carfilzomib-Rd (KRd) and daratumumab-Rd (DaraRd), represent a standard of care in lenalidomide-sensitive multiple myeloma (MM) patients in first relapse. Meta-analysis of randomized clinical trials (RCT), suggested better outcome with DaraRd. Trying to address this issue in clinical practice, we collected data of 430 consecutive MM patients addressed to Rd-based triplets in first relapse between January 2017 and March 2021. Overall, the most common used regimen was DaraRd, chosen in almost half of the cases (54.4%), followed by KRd (34.6%). Different triplets were used much less commonly. In an attempt to limit the imbalance of a retrospective analysis, we conducted a propensity score matching (PSM) comparison between DaraRd and KRd. After PSM, efficacy of DaraRd versus KRd was similar in terms of overall-response rate (ORR) (OR: 0.9, P=0.685) as well as of very good partial response (VGPR) or better (OR: 0.9, P=0.582). The median progression-free survival (PFS) was significantly longer for DaraRd (29.8 vs. 22.5 months; P=0.028). DaraRd was tolerated better, registering a lower rate of grade 3-4 non-hematological toxicity (OR: 0.4, P
- Published
- 2023
24. The role of autologous stem-cell transplantation in multiple myeloma in 2021
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Roberto Mina and Francesca Gay
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Melphalan ,Oncology ,Cancer Research ,medicine.medical_specialty ,Standard of care ,business.industry ,MEDLINE ,Newly diagnosed ,Plasma cell ,medicine.disease ,Transplantation ,medicine.anatomical_structure ,Autologous stem-cell transplantation ,Internal medicine ,medicine ,Humans ,Multiple Myeloma ,business ,Antineoplastic Agents, Alkylating ,Multiple myeloma ,Randomized Controlled Trials as Topic ,Stem Cell Transplantation ,medicine.drug - Abstract
Purpose of review In this review, we discuss the most important aspects of the role of high-dose melphalan (HDM) and autologous stem-cell transplantation (ASCT) in the treatment of multiple myeloma (MM). Recent findings Almost 40 years after the publication of the first study on safety and efficacy of HDM and ASCT in MM patients, and despite the introduction of several drugs and combinations with various targets on the plasma cell and the surrounding microenvironment, HDM-ASCT still stands as a standard of care for the upfront treatment of newly diagnosed MM patients. Indeed, all attempts to replace HDM-ASCT with novel-agent-based, non-transplant strategies have failed to demonstrate their efficacy, at least in terms of progression-free survival. Summary Despite such a long history in MM, a number of open issues regarding HDM-ASCT still exist, from the choice between using transplant in first-line therapy or at relapse to the use of tandem HDM-ASCT in high-risk patients. With the introduction of more and more effective multidrug regimens and of novel immunotherapeutic approaches, the challenge between transplant and non-transplant is not over yet.
- Published
- 2021
25. Daratumumab-Based Therapy for IgM Multiple Myeloma With Hyperviscosity Syndrome: A Case Report
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Roberto Mina, Francesca Bonello, Francesca Gay, Elena Zamagni, Mario Boccadoro, Mina R., Bonello F., Gay F., Zamagni E., and Boccadoro M.
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Oncology ,Cancer Research ,medicine.medical_specialty ,IgM ,business.industry ,medicine.medical_treatment ,Hyperviscosity syndrome ,Daratumumab ,Plasmapheresis ,Hematology ,medicine.disease ,Multiple myeloma ,Internal medicine ,Medicine ,business - Abstract
NA
- Published
- 2021
26. A prognostic model for patients with lymphoma and COVID-19: a multicentre cohort study
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Francesco Merli, Carlo Visco, Annarita Conconi, Daniele Vallisa, Elettra Ortu La Barbera, Sara Galimberti, Roberto Mina, Marianna Sassone, Anna Guidetti, Adriano Venditti, Alessandro Corso, Francesco Marchesi, Pellegrino Musto, Agostino Tafuri, Valentina Bonuomo, Filippo Gherlinzoni, Francesco Lanza, Monia Marchetti, Safaa M. Ramadan, Marco Salvini, Massimo Massaia, Elisa Coviello, Alessandro Busca, Luigi Petrucci, Daniele Armiento, Mauro Turrini, Alessandra Romano, Chiara Cattaneo, Francesco Passamonti, Matteo G. Della Porta, Anna Candoni, Luigi Rigacci, Luca Arcaini, Livio Trentin, Valeria Cardinali, Maria Chiara Tisi, Carmine Selleri, Carlo Gambacorti-Passerini, Andrés J.M. Ferreri, Patrizia Tosi, Riccardo Bruna, Mauro Krampera, Antonio Cuneo, Nicola Stefano Fracchiolla, Daniela Cilloni, Lorenza Bertù, Paolo Corradini, Annamaria Scattolin, Roberto Cairoli, Giuseppe Visani, Domenico Penna, Marco Ladetto, Antonello Pinto, Michele Cavo, Monica Bocchia, Sofia Pilerci, Luigi Marcheselli, Visco, C, Marcheselli, L, Mina, R, Sassone, M, Guidetti, A, Penna, D, Cattaneo, C, Bonuomo, V, Busca, A, Ferreri, A, Bruna, R, Petrucci, L, Cairoli, R, Salvini, M, Bertu, L, Ladetto, M, Pilerci, S, Pinto, A, Ramadan, S, Marchesi, F, Cavo, M, Arcaini, L, Coviello, E, Romano, A, Musto, P, Massaia, M, Fracchiolla, N, Marchetti, M, Scattolin, A, Tisi, M, Cuneo, A, Porta, M, Trentin, L, Turrini, M, Gherlinzoni, F, Tafuri, A, Galimberti, S, Bocchia, M, Cardinali, V, Cilloni, D, Corso, A, Armiento, D, Rigacci, L, La Barbera, E, Gambacorti Passerini, C, Visani, G, Vallisa, D, Venditti, A, Selleri, C, Conconi, A, Tosi, P, Lanza, F, Candoni, A, Krampera, M, Corradini, P, Passamonti, F, and Merli, F
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Adult ,medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,Aged ,Aged, 80 and over ,Cohort Studies ,Humans ,Middle Aged ,Prognosis ,SARS-CoV-2 ,Young Adult ,COVID-19 ,Lymphoma ,Lymphocyte ,medicine.medical_treatment ,Disease ,NO ,lymphoma, COVID-19, multicentre cohort study, SARS-CoV-2 ,Internal medicine ,medicine ,80 and over ,lymphoma ,covid-19 ,anti-cd20 ,business.industry ,Regular Article ,Immunosuppression ,Hematology ,Settore MED/15 ,medicine.disease ,medicine.anatomical_structure ,Cohort ,Prognostic model ,business ,Cohort study - Abstract
Lymphoma represents a heterogeneous hematological malignancy (HM), which is characterized by severe immunosuppression. Patients diagnosed of coronavirus disease 2019 (COVID-19) during the course of HM have been described to have poor outcome, with only few reports specifically addressing lymphoma patients. Here, we investigated the clinical behavior and clinical parameters of a large multicenter cohort of adult patients with different lymphoma subtypes, with the aim of identifying predictors of death. The study included 856 patients, of whom 619 were enrolled prospectively in a 1-year frame and were followed-up for a median of 66 days (range 1-395). Patients were managed as outpatient (not-admitted cohort, n = 388) or required hospitalization (n = 468), and median age was 63 years (range 19-94). Overall, the 30- and 100-days mortality was 13% (95% confidence interval (CI), 11% to 15%) and 23% (95% CI, 20% to 27%), respectively. Antilymphoma treatment, including anti-CD20 containing regimens, did not impact survival. Patients with Hodgkin’s lymphoma had the more favorable survival, but this was partly related to significantly younger age. The time interval between lymphoma diagnosis and COVID-19 was inversely related to mortality. Multivariable analysis recognized 4 easy-to-use factors (age, gender, lymphocyte, and platelet count) that were associated with risk of death, both in the admitted and in the not-admitted cohort (HR 3.79 and 8.85 for the intermediate- and high-risk group, respectively). Overall, our study shows that patients should not be deprived of the best available treatment of their underlying disease and indicates which patients are at higher risk of death. This study was registered with ClinicalTrials.gov, NCT04352556.
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- 2022
27. SARS-CoV-2 infection in patients with chronic lymphocytic leukemia: The Italian Hematology Alliance on COVID-19 cohort
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Michele Merli, Isacco Ferrarini, Francesco Merli, Alessandro Busca, Roberto Mina, Brunangelo Falini, Riccardo Bruna, Roberto Cairoli, Monia Marchetti, Alessandra Romano, Michele Cavo, Luca Arcaini, Livio Trentin, Chiara Cattaneo, Enrico Derenzini, Nicola Stefano Fracchiolla, Francesco Marchesi, Annamaria Scattolin, Atto Billio, Monica Bocchia, Massimo Massaia, Carlo Gambacorti‐Passerini, Francesca Romana Mauro, Massimo Gentile, Sara Mohamed, Matteo Giovanni Della Porta, Elisa Coviello, Daniela Cilloni, Giuseppe Visani, Augusto Bramante Federici, Maria Chiara Tisi, Laura Cudillo, Sara Galimberti, Filippo Gherlinzoni, Livio Pagano, Anna Guidetti, Lorenza Bertù, Paolo Corradini, Francesco Passamonti, Carlo Visco, Merli, M, Ferrarini, I, Merli, F, Busca, A, Mina, R, Falini, B, Bruna, R, Cairoli, R, Marchetti, M, Romano, A, Cavo, M, Arcaini, L, Trentin, L, Cattaneo, C, Derenzini, E, Fracchiolla, N, Marchesi, F, Scattolin, A, Billio, A, Bocchia, M, Massaia, M, Gambacorti-Passerini, C, Mauro, F, Gentile, M, Mohamed, S, Della Porta, M, Coviello, E, Cilloni, D, Visani, G, Federici, A, Tisi, M, Cudillo, L, Galimberti, S, Gherlinzoni, F, Pagano, L, Guidetti, A, Bertu, L, Corradini, P, Passamonti, F, and Visco, C
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Settore MED/15 - MALATTIE DEL SANGUE ,Cancer Research ,BTK inhibitors ,Oncology ,chronic lymphocytic leukemia ,COVID-19 ,outcome ,SARS-CoV-2 ,BTK inhibitor ,Hematology ,General Medicine - Abstract
COVID-19, the disease caused by SARS-CoV-2, is still afflicting thousands of people across the globe. Few studies on COVID-19 in chronic lymphocytic leukemia (CLL) are available. Here, we analyzed data from the CLL cohort of the Italian Hematology Alliance on COVID-19 (NCT04352556), which included 256 CLL patients enrolled between 25 February 2020 and 1 February 2021. Median age was 70 years (range 38–94) with male preponderance (60.1%). Approximately half of patients (n = 127) had received at least one line of therapy for CLL, including 108 (83.7%) who were on active treatment at the time of COVID-19 or received their last therapy within 12 months. Most patients (230/256, 89.9%) were symptomatic at COVID-19 diagnosis and the majority required hospitalization (n = 176). Overall, after a median follow-up of 42 days (IQR 24–96), case fatality rate was 30.1%, and it was 37.5% and 24.4% in the first (25 February 2020–22 June 2020) and second wave (23 June 2020–1 February 2021), respectively (p = 0.03). At multivariate analysis, male sex (HR 1.82, 95% CI 1.03–3.24, p = 0.04), age over than 70 years (HR 2.23, 95% CI 1.23–4.05, p = 0.01), any treatment for CLL given in the last 12 months (HR 1.72, 95% CI 1.04–2.84, p = 0.04) and COVID-19 severity (severe: HR 5.66, 95% CI 2.62–12.33, p < 0.0001; critical: HR 15.99, 95% CI 6.93–36.90, p < 0.0001) were independently associated with poor survival. In summary, we report a dismal COVID-related outcome in a significant fraction of CLL patients, that can be nicely predicted by clinical parameters.
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- 2022
28. Anti-CD38 monoclonal antibodies in multiple myeloma: another cook in the kitchen?
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Mattia D'Agostino, Roberto Mina, and Francesca Gay
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biology ,business.industry ,medicine.drug_class ,Antibodies, Monoclonal ,Hematology ,CD38 ,medicine.disease ,Monoclonal antibody ,Immunology ,Monoclonal ,medicine ,biology.protein ,Humans ,Antibody ,Multiple Myeloma ,business ,Multiple myeloma - Published
- 2020
29. Once-weekly versus twice-weekly carfilzomib in patients with newly diagnosed multiple myeloma: a pooled analysis of two phase I/II studies
- Author
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Maria Teresa Petrucci, Mario Boccadoro, Roberto Mina, Massimo Offidani, Pellegrino Musto, Vittorio Montefusco, Stefano Spada, Elena Ponticelli, Giulia Benevolo, Piero Galieni, Antonio Palumbo, Gianluca Gaidano, Michele Cavo, Sara Bringhen, Tommaso Caravita di Toritto, Francesco Di Raimondo, Stelvio Ballanti, Alessandra Larocca, Bringhen, Sara, Mina, Roberto, Petrucci, Maria Teresa, Gaidano, Gianluca, Ballanti, Stelvio, Musto, Pellegrino, Offidani, Massimo, Spada, Stefano, Benevolo, Giulia, Ponticelli, Elena, Galieni, Piero, Cavo, Michele, Di Toritto, Tommaso Caravita, Di Raimondo, Francesco, Montefusco, Vittorio, Palumbo, Antonio, Boccadoro, Mario, and Larocca, Alessandra
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Male ,medicine.medical_specialty ,Cyclophosphamide ,Antineoplastic Agents ,carfilzomib,multiple myeloma ,Gastroenterology ,Article ,Plasma Cell Disorders ,Drug Administration Schedule ,Maintenance Chemotherapy ,chemistry.chemical_compound ,Maintenance therapy ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Medicine ,Humans ,Adverse effect ,Survival analysis ,Multiple myeloma ,Dexamethasone ,Aged ,Aged, 80 and over ,business.industry ,Induction chemotherapy ,Hematology ,Induction Chemotherapy ,Middle Aged ,medicine.disease ,Prognosis ,Carfilzomib ,Survival Analysis ,Treatment Outcome ,chemistry ,Female ,business ,Multiple Myeloma ,Oligopeptides ,medicine.drug - Abstract
Twice-weekly carfilzomib is approved at 27 and 56 mg/m(2) to treat relapsed multiple myeloma patients. In the phase III study ARROW, once-weekly 70 mg/m 2 carfilzomib prolonged the median progression-free survival of relapsed multiple myeloma patients in comparison with twice-weekly 27 mg/m(2) carfilzomib, without adding significant toxicity. Data were pooled from two phase I/II studies of newly diagnosed multiple myeloma patients who received nine induction cycles of carfilzomib (either 70 mg/m(2) once-weekly or 36 mg/m(2) twice-weekly), cyclophosphamide and dexamethasone, followed by carfilzomib maintenance. Overall, 121 transplant-ineligible patients with newly diagnosed multiple myeloma were analyzed (once-weekly, n=63; twice-weekly, n=58). We found no significant difference in median progression-free survival [35.7 months (95%CI: 23.7-not reached, NR) vs 35.5 months (95%CI: 24.3-NR); HR: 1.39; P=0.26] and 3-year overall survival [70% [95%CI: 59%-84%) vs 72% (95%CI: 60%-85%); HR: 1.27; P=0.5] between once-weekly and twice-weekly carfilzomib. From the start of maintenance, 3-year progression-free survival [47% (95%CI: 33%-68%) vs 51% (95%CI: 38%-70%); HR: 1.04; P=0.92] and overall survival [72% (95%CI: 58%-89%) vs 73% (95%CI: 59%-90%); HR: 0.82; P=0.71] were similar in the once- versus twice-weekly carfilzomib. The rate of grade 3-5 hematologic (24% vs 30%; P=0.82) and non-hematologic (38% vs 41%; P=0.83) adverse events was similar in the two groups. Once-weekly 70 mg/m(2) carfilzomib as induction and maintenance therapy for newly diagnosed multiple myeloma patients was as safe and effective as twice-weekly 36 mg/m(2) carfilzomib and provided a more convenient schedule. The trials are registered at clinicaltrials.gov identifiers: 01857115 (IST-CAR-561) and 01346787 (IST-CAR-506).
- Published
- 2019
30. Development and Validation of a Simplified Score to Predict Early Relapse in Newly Diagnosed Multiple Myeloma in a Pooled Dataset of 2,190 Patients
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Gian Maria Zaccaria, Luca Bertamini, Maria Teresa Petrucci, Massimo Offidani, Paolo Corradini, Andrea Capra, Alessandra Romano, Anna Marina Liberati, Donato Mannina, Paolo de Fabritiis, Nicola Cascavilla, Marina Ruggeri, Roberto Mina, Francesca Patriarca, Giulia Benevolo, Angelo Belotti, Gianluca Gaidano, Arnon Nagler, Roman Hájek, Andrew Spencer, Pieter Sonneveld, Pellegrino Musto, Mario Boccadoro, and Francesca Gay
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Oncology ,Cancer Research ,medicine.medical_specialty ,Time Factors ,Datasets as Topic ,Early Relapse ,Newly diagnosed ,03 medical and health sciences ,0302 clinical medicine ,Text mining ,Recurrence ,Internal medicine ,medicine ,Humans ,Multiple myeloma ,Aged ,Univariate analysis ,business.industry ,Middle Aged ,Settore MED/15 ,Prognosis ,medicine.disease ,Response to treatment ,Survival Rate ,Clinical trial ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Bone marrow ,Multiple Myeloma ,business ,030215 immunology - Abstract
Purpose: Despite the improvement of therapeutic regimens, several patients with multiple myeloma (MM) still experience early relapse (ER). This subset of patients currently represents an unmet medical need. Experimental Design: We pooled data from seven European multicenter phase II/III clinical trials enrolling 2,190 patients with newly diagnosed MM from 2003 to 2017. Baseline patient evaluation included 14 clinically relevant features. Patients with complete data (n = 1,218) were split into training (n = 844) and validation sets (n = 374). In the training set, a univariate analysis and a multivariate logistic regression model on ER within 18 months (ER18) were made. The most accurate model was selected on the validation set. We also developed a dynamic version of the score by including response to treatment. Results: The Simplified Early Relapse in Multiple Myeloma (S-ERMM) score was modeled on six features weighted by a score: 5 points for high lactate dehydrogenase or t(4;14); 3 for del17p, abnormal albumin, or bone marrow plasma cells >60%; and 2 for λ free light chain. The S-ERMM identified three patient groups with different risks of ER18: Intermediate (Int) versus Low (OR = 2.39, P < 0.001) and High versus Low (OR = 5.59, P < 0.001). S-ERMM High/Int patients had significantly shorter overall survival (High vs. Low: HR = 3.24, P < 0.001; Int vs. Low: HR = 1.86, P < 0.001) and progression-free survival-2 (High vs. Low: HR = 2.89, P < 0.001; Int vs. Low: HR = 1.76, P < 0.001) than S-ERMM Low. The Dynamic S-ERMM (DS-ERMM) modulated the prognostic power of the S-ERMM. Conclusions: On the basis of simple, widely available baseline features, the S-ERMM and DS-ERMM properly identified patients with different risks of ER and survival outcomes.
- Published
- 2021
31. Antibody-drug conjugates: when chemotherapy meets immuno-oncology
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Roberto Mina and Francesca Gay
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Drug ,Oncology ,Chemotherapy ,medicine.medical_specialty ,Immunoconjugates ,biology ,business.industry ,medicine.medical_treatment ,media_common.quotation_subject ,Hematology ,Medical Oncology ,Internal medicine ,Neoplasms ,medicine ,biology.protein ,Humans ,Antibody ,business ,media_common - Published
- 2021
32. Carfilzomib, cyclophosphamide and dexamethasone for newly diagnosed, high-risk myeloma patients not eligible for transplant: a pooled analysis of two studies
- Author
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Concetta Conticello, Michele Cavo, Sara Bringhen, Milena Gilestro, Maria Teresa Petrucci, Stelvio Ballanti, Gianluca Gaidano, Roberto Mina, Pellegrino Musto, Antonio Palumbo, Andrea Capra, Vittorio Montefusco, Giulia Benevolo, Anna Marina Liberati, Mario Boccadoro, Agostina Siniscalchi, Paola Omedè, Attilio Olivieri, Francesca Bonello, Piero Galieni, Mina R., Bonello F., Petrucci M.T., Liberati A.M., Conticello C., Ballanti S., Musto P., Olivieri A., Benevolo G., Capra A., Gilestro M., Galieni P., Cavo M., Siniscalchi A., Palumbo A., Montefusco V., Gaidano G., Omede P., Boccadoro M., and Bringhen S.
- Subjects
Oncology ,medicine.medical_specialty ,Cyclophosphamide ,dexamethasone ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Text mining ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Medicine ,In Situ Hybridization, Fluorescence ,Multiple myeloma ,Dexamethasone ,Antineoplastic Combined Chemotherapy Protocol ,carfilzomib ,medicine.diagnostic_test ,business.industry ,Cytogenetics ,Hematology ,medicine.disease ,Carfilzomib ,Treatment Outcome ,chemistry ,Multiple Myeloma ,cyclophosphamide ,high-risk cytogenetic abnormalities ,030220 oncology & carcinogenesis ,Meta-analysis ,Oligopeptide ,business ,Oligopeptides ,Human ,030215 immunology ,medicine.drug ,Fluorescence in situ hybridization - Abstract
Despite remarkable advances in the treatment of multiple myeloma in the last decades, the prognosis of patients harboring high-risk cytogenetic abnormalities remains dismal as compared to that of standard-risk patients. Proteasome inhibitors demonstrated to partially ameliorate the prognosis of high-risk patients. We pooled together data from two phase I/II trials on transplant-ineligible patients with multiple myeloma receiving upfront carfilzomib cyclophosphamide and dexamethasone followed by carfilzomib maintenance. The aim of this analysis was to compare treatment outcomes in patients with standard- versus high-risk cytogenetic abnormalities detected by fluorescence in situ hybridization (FISH) analysis. High risk was defined by the presence of at least one chromosomal abnormality, including t(4;14), del17p and t(14;16). Overall, 94 patients were included in the analysis: 57 (61%) in the standard-risk and 37 (39%) in the high-risk group. Median follow-up was 38 months. In standard- vs. high-risk patients, we observed similar progression-free survival (3-year PFS: 52% vs. 43%, respectively; p=0.50), overall survival (3-year OS: 78% vs. 73%; p=0.38), and overall response rate (88% vs 95%; p=0.47), with no statistical differences between the two groups. No difference in terms of progression-free survival was observed between patients with or without del17p. Carfilzomib, used both as induction and maintenance agent for transplant-ineligible newly diagnosed multiple myeloma patients, mitigated the poor prognosis carried by high-risk cytogenetics and resulted into similar progression-free survival and overall survival, as compared to standard-risk patients. ClinicalTrials.gov IDs: NCT01857115 (IST-CAR-561) and NCT01346787 (IST-CAR-506).
- Published
- 2021
33. COVID-19 elicits an impaired antibody response against SARS-CoV-2 in patients with haematological malignancies
- Author
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Francesco Zaja, Filippo Gherlinzoni, Anna Maria Scattolin, Luca Arcaini, Roberto Cairoli, Mario Luppi, Carmen Fava, Patrizia Zappasodi, Matteo G. Della Porta, Monica Bocchia, Valeria Cardinali, Nicola Stefano Fracchiolla, Francesco Passamonti, Giuseppe Visani, M. Ladetto, Enrico Derenzini, Lorenza Bertù, Roberto Mina, Daniele Armiento, B. Mora, Anna Candoni, Alessandro Corso, A. M. Vannucchi, Paolo Corradini, Francesco Lanza, Pellegrino Musto, Agostino Tafuri, Carlo Visco, E. Coviello, Francesco Marchesi, Roberto M. Lemoli, Chiara Cattaneo, Alessandro Busca, Marco Salvini, Sara Galimberti, I. Romano, M. Merli, Mauro Krampera, Alessandra Romano, Paolo Grossi, Michele Cavo, E. O. La Barbera, Mauro Turrini, Livio Pagano, Adriano Venditti, Antonio Pinto, Patrizia Tosi, F. Farina, Riccardo Bruna, L. Petrucci, Massimo Massaia, Monia Marchetti, Carlo Gambacorti Passerini, Francesco Merli, Passamonti, F, Romano, A, Salvini, M, Merli, F, Porta, M, Bruna, R, Coviello, E, Romano, I, Cairoli, R, Lemoli, R, Farina, F, Venditti, A, Busca, A, Ladetto, M, Massaia, M, Pinto, A, Arcaini, L, Tafuri, A, Marchesi, F, Fracchiolla, N, Bocchia, M, Armiento, D, Candoni, A, Krampera, M, Luppi, M, Cardinali, V, Galimberti, S, Cattaneo, C, La Barbera, E, Mina, R, Lanza, F, Visani, G, Musto, P, Petrucci, L, Zaja, F, Grossi, P, Bertu, L, Pagano, L, Corradini, P, Derenzini, E, Marchetti, M, Scattolin, A, Corso, A, Tosi, P, Gherlinzoni, F, Gambacorti Passerini, C, Cavo, M, Fava, C, Turrini, M, Visco, C, Zappasodi, P, Merli, M, Mora, B, Vannucchi, A, Passamonti F., Romano A., Salvini M., Merli F., Porta M.G.D., Bruna R., Coviello E., Romano I., Cairoli R., Lemoli R., Farina F., Venditti A., Busca A., Ladetto M., Massaia M., Pinto A., Arcaini L., Tafuri A., Marchesi F., Fracchiolla N., Bocchia M., Armiento D., Candoni A., Krampera M., Luppi M., Cardinali V., Galimberti S., Cattaneo C., La Barbera E.O., Mina R., Lanza F., Visani G., Musto P., Petrucci L., Zaja F., Grossi P.A., Bertu L., Pagano L., Corradini P., Derenzini E., Marchetti M., Scattolin A.M., Corso A., Tosi P., Gherlinzoni F., Passerini C.G., Cavo M., Fava C., Turrini M., Visco C., Zappasodi P., Merli M., Mora B., Vannucchi A.M., Passamonti, F., Romano, A., Salvini, M., Merli, F., Porta, M. G. D., Bruna, R., Coviello, E., Romano, I., Cairoli, R., Lemoli, R., Farina, F., Venditti, A., Busca, A., Ladetto, M., Massaia, M., Pinto, A., Arcaini, L., Tafuri, A., Marchesi, F., Fracchiolla, N., Bocchia, M., Armiento, D., Candoni, A., Krampera, M., Luppi, M., Cardinali, V., Galimberti, S., Cattaneo, C., La Barbera, E. O., Mina, R., Lanza, F., Visani, G., Musto, P., Petrucci, L., Zaja, F., Grossi, P. A., Bertu, L., Pagano, L., Corradini, P., Derenzini, E., Marchetti, M., Scattolin, A. M., Corso, A., Tosi, P., Gherlinzoni, F., Passerini, C. G., Cavo, M., Fava, C., Turrini, M., Visco, C., Zappasodi, P., Merli, M., Mora, B., and Vannucchi, A. M.
- Subjects
Male ,Myeloid ,Antibodies, Viral ,Gastroenterology ,SARS‐CoV‐2 ,80 and over ,Covid-19 ,SARS-CoV-2 ,leukemia ,lymphoma ,myeloma ,Viral ,Covid‐19 ,Aged, 80 and over ,biology ,Hematology ,Plasma cell neoplasm ,Middle Aged ,Adult ,Aged ,COVID-19 ,Female ,Hematologic Neoplasms ,Humans ,Immunoglobulin G ,Seroconversion ,Young Adult ,Antibody Formation ,Leukemia ,medicine.anatomical_structure ,Antibody ,Human ,medicine.medical_specialty ,Short Report ,Antibodies ,NO ,Chemoimmunotherapy ,Internal medicine ,medicine ,Hematologic Neoplasm ,business.industry ,Odds ratio ,Settore MED/15 ,medicine.disease ,Covid-19, SARS-CoV-2, leukemia, lymphoma, myeloma ,Lymphoma ,Settore MED/15 - MALATTIE DEL SANGUE ,biology.protein ,business - Abstract
COVID-19 is associated with high mortality in patients with haematological malignancies (HM) and rate of seroconversion is unknown. The ITA-HEMA-COV project (NCT04352556) investigated patterns of seroconversion for SARS-CoV-2 IgG in patients with HMs. A total of 237 patients, SARS-CoV-2 PCR-positive with at least one SARS-CoV-2 IgG test performed during their care, entered the analysis. Among these, 62 (26·2%) had myeloid, 121 (51·1%) lymphoid and 54 (22·8%) plasma cell neoplasms. Overall, 69% of patients (164 of 237) had detectable IgG SARS-CoV-2 serum antibodies. Serologically negative patients (31%, 73 of 237) were evenly distributed across patients with myeloid, lymphoid and plasma cell neoplasms. In the multivariable logistic regression, chemoimmunotherapy [odds ratio (OR), 3·42; 95% confidence interval (CI), 1·04–11·21; P=0·04] was associated with a lower rate of seroconversion. This effect did not decline after 180days from treatment withdrawal (OR, 0·35; 95% CI: 0·11–1·13; P=0·08). This study demonstrates a low rate of seroconversion in HM patients and indicates that treatment-mediated immune dysfunction is the main driver. As a consequence, we expect a low rate of seroconversion after vaccination and thus we suggest testing the efficacy of seroconversion in HM patients.
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- 2021
34. Minimal Residual Disease in Multiple Myeloma: Ready for Prime Time?
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Francesca Bonello, Roberto Mina, and Stefania Oliva
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Cancer Research ,medicine.medical_specialty ,Neoplasm, Residual ,MRD Negativity ,Bone Marrow ,hemic and lymphatic diseases ,Clinical endpoint ,Humans ,Medicine ,multiple myeloma (MM) ,Intensive care medicine ,next-generation sequencing (NGS) ,Multiple myeloma ,business.industry ,Endpoints ,minimal residual disease (MRD) ,multiparameter flow cytometry (MFC) ,positron emission tomography/computed tomography (PET/CT) ,Prognosis ,medicine.disease ,Minimal residual disease ,body regions ,Clinical Practice ,Clinical trial ,medicine.anatomical_structure ,Oncology ,Treatment strategy ,Bone marrow ,Multiple Myeloma ,business - Abstract
Minimal residual disease (MRD) techniques are essential to identify the small clonal fraction within and outside the bone marrow. In the last years, evidence regarding their prognostic role for the evaluation of the depth of response of current treatment strategies has grown rapidly. Consequently, MRD was incorporated in an increasing number of clinical trials for multiple myeloma patients, also as primary endpoint, and even to guide therapeutic choices. A robust correlation between MRD negativity and survival was established. Yet, several issues regarding MRD evaluation remain to be addressed: from the optimal and more cost-effective techniques for its assessment and its harmonization worldwide to its use in clinical practice to its impact on treatment modulation. This review focuses on the available evidence supporting the use of MRD status for the management of multiple myeloma patients and on open issues that still need an answer.
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- 2021
35. Minimal Residual Disease in Multiple Myeloma: State of the Art and Future Perspectives
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Mario Boccadoro, Stefania Oliva, and Roberto Mina
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Oncology ,medicine.medical_specialty ,MRD Negativity ,lcsh:Medicine ,Review ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,hemic and lymphatic diseases ,medicine ,Overall survival ,Multiple myeloma ,Complete response ,030304 developmental biology ,0303 health sciences ,business.industry ,Surrogate endpoint ,lcsh:R ,next-generation flow ,General Medicine ,medicine.disease ,Minimal residual disease ,Clinical trial ,Clinical Practice ,body regions ,multiple myeloma ,030220 oncology & carcinogenesis ,minimal residual disease ,next-generation sequencing ,Erratum ,business - Abstract
Minimal residual disease (MRD) detection represents a sensitive tool to appropriately measure the response obtained with therapies for multiple myeloma (MM). The achievement of MRD negativity has superseded the conventional complete response (CR) and has been proposed as a surrogate endpoint for progression-free survival and overall survival. Several techniques are available for the detection of MRD inside (next-generation sequencing, flow cytometry) and outside (PET/CT, magnetic resonance) the bone marrow, and their complementary use allows a precise definition of the efficacy of anti-myeloma treatments. This review summarizes MRD data and results from previous clinical trials, highlights open issues related to the role of MRD in MM and discusses how MRD could be implemented in clinical practice to inform on patient prognosis and drive therapeutic decisions.
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- 2020
36. A longitudinal analysis of chromosomal abnormalities in disease progression from MGUS/SMM to newly diagnosed and relapsed multiple myeloma
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Elona Saraci, Marina Ruggeri, Gloria Margiotta Casaluci, Milena Gilestro, Daniela Oddolo, Stefania Oliva, Elisa Genuardi, Paola Omedè, Rossella Troia, S. Caltagirone, Roberto Mina, Lorenzo De Paoli, Sara Bringhen, Mario Boccadoro, and Mattia D'Agostino
- Subjects
Male ,Smoldering Multiple Myeloma ,medicine.medical_treatment ,Gastroenterology ,Monoclonal Gammopathy of Undetermined Significance ,Leukemia, Plasma Cell ,0302 clinical medicine ,Multiple myeloma ,Risk Factors ,Medicine ,Chromosomes, Human ,Longitudinal Studies ,Cytogenetic abnormalities ,Plasma cell leukemia ,Leukemia ,Hematology ,medicine.diagnostic_test ,Fluorescence in situ hybridization ,General Medicine ,Middle Aged ,Survival Rate ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Plasma Cell ,Female ,Human ,medicine.medical_specialty ,Chromosomes ,Disease-Free Survival ,Clonal Evolution ,03 medical and health sciences ,FISH ,Internal medicine ,Humans ,Aged ,Retrospective Studies ,Chromosome Aberrations ,Disease progression ,Chemotherapy ,business.industry ,medicine.disease ,Clonal evolution ,Follow-Up Studies ,Bone marrow ,business ,Progressive disease ,Monoclonal gammopathy of undetermined significance ,030215 immunology - Abstract
We analyzed variations in terms of chromosomal abnormalities (CA) by fluorescence in situ hybridization (FISH) analysis on purified bone marrow plasma cells throughout the progression from monoclonal gammopathy of undetermined significance/smoldering multiple myeloma (MGUS/SMM) to newly diagnosed MM/plasma cell leukemia (NDMM/PCL) at diagnosis and from diagnostic samples to progressive disease. High risk was defined by the presence of at least del(17p), t(4;14), and/or t(14;16). 1p/1q detection (in the standard FISH panel from 2012 onward) was not available for all patients. We analyzed 139 MM/PCL diagnostic samples from 144 patients, with a median follow-up of 71 months: high-risk CA at diagnosis (MGUS/SMM or NDMM) was present in 28% of samples, whereas 37–39% showed high-risk CA at relapse. In 115 patients with NDMM who evolved to relapsed/refractory MM, we identified 3 different populations: (1) 31/115 patients (27%) with gain of new CA (del13, del17p, t(4;14), t(14;16) or 1q CA when available); (2) 10/115 (9%) patients with loss of a previously identified CA; and (3) 74 patients with no changes. The CA gain group showed a median overall survival of 66 months vs. 84 months in the third group (HR 0.56, 95% CI 0.34–0.92, p = 0.023). Clonal evolution occurs as disease progresses after different chemotherapy lines. Patients who acquired high-risk CA had the poorest prognosis. Our findings highlight the importance of performing FISH analysis both at diagnosis and at relapse.
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- 2020
37. IXAZOMIB WITH EITHER DEXAMETHASONE, CYCLOPHOSPHAMIDE-DEXAMETHASONE, THALIDOMIDE-DEXAMETHASONE OR BENDAMUSTINE-DEXAMETHASONE FOLLOWED BY IXAZOMIB MAINTENANCE IN ELDERLY NEWLY DIAGNOSED MYELOMA PATIENTS
- Author
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Roberto, Mina, Alessandra, Larocca, Paolo, Corradini, Nicola, Cascavilla, Anna Marina Liberati, Norbert, Pescosta, Maria Teresa Petrucci, Giovannino, Ciccone, Andrea, Capra, Francesca, Patriarca, Delia, Rota-Scalabrini, Innao, Vanessa, Annalisa, Bernardini, Michele, Cea, Renato, Zambello, Anna, Baraldi, Angelo, Belotti, Claudia, Cellini, Monica, Galli, Mariella, Grasso, Sara, Aquino, Gloria Margiotta Casaluci, Giovanni De Sabbata, Stelvio, Ballanti, Massimo, Offidani, Mancuso, Katia, Mario, Boccadoro, and Sara, Bringhen
- Subjects
Elderly, Multiple myeloma ,Elderly ,Multiple myeloma - Published
- 2020
38. Should high-risk smouldering multiple myeloma be treated?
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Mario Boccadoro, Roberto Mina, Sundar Jagannath, and Shambavi Richard
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Oncology ,Smouldering ,medicine.medical_specialty ,business.industry ,Internal medicine ,medicine ,Hematology ,business ,medicine.disease ,Multiple myeloma - Published
- 2020
39. Bortezomib-dexamethasone as maintenance therapy or early retreatment at biochemical relapse versus observation in relapsed/refractory multiple myeloma patients: a randomized phase II study
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Mariella Grasso, Federico Monaco, Stelvio Ballanti, Alessandra Romano, Paolo de Fabritiis, Mario Boccadoro, Roberto Ria, Giacomo Di Lullo, Massimo Offidani, Monia Marchetti, Norbert Pescosta, Nicola Giuliani, Andrea Capra, Pieter Sonneveld, Roberto Mina, Renato Zambello, Marco Gobbi, Maria Letizia Mosca-Siez, Angelo Belotti, Sonia Ronconi, Pellegrino Musto, Claudia Cellini, Maria Teresa Petrucci, Alessandra Larocca, Anna Marina Liberati, and Hematology
- Subjects
Oncology ,Male ,medicine.medical_specialty ,Aged ,Antineoplastic Agents ,Bortezomib ,Dexamethasone ,Female ,Humans ,Multiple Myeloma ,Neoplasm Recurrence, Local ,Survival Analysis ,Phases of clinical research ,Myeloma ,lcsh:RC254-282 ,Phase II trials ,law.invention ,Text mining ,Maintenance therapy ,Randomized controlled trial ,law ,Internal medicine ,Correspondence ,medicine ,Survival analysis ,Multiple myeloma ,business.industry ,Hematology ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Settore MED/15 ,Clinical trial ,Neoplasm Recurrence ,Local ,Biochemical relapse ,business - Published
- 2020
40. Clinical features and survival of multiple myeloma patients harboring t(14;16) in the era of novel agents
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Lawrence H. Boise, Stefania Oliva, Lorenzo De Paoli, Paola Omedè, Roberto Mina, Angelo Belotti, Mario Boccadoro, Evangelos Terpos, Nisha Joseph, Francesca Patriarca, Efstathios Kastritis, Meletios A. Dimopoulos, David L. Jaye, Nicola Giuliani, Massimo Offidani, Maria Gavriatopoulou, Maria Teresa Petrucci, Maria Roussou, Vittorio Montefusco, Jonathan L. Kaufman, Ajay K. Nooka, and Sagar Lonial
- Subjects
Adult ,Male ,MEDLINE ,Myeloma ,Chromosomal translocation ,Transplantation, Autologous ,lcsh:RC254-282 ,Translocation, Genetic ,Medical research ,Correspondence ,Humans ,Medicine ,Survival rate ,Multiple myeloma ,Aged ,Aged, 80 and over ,Chromosomes, Human, Pair 14 ,business.industry ,Hematopoietic Stem Cell Transplantation ,Hematology ,Middle Aged ,Prognosis ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Survival Rate ,Transplantation ,Oncology ,Novel agents ,Cancer research ,Female ,Multiple Myeloma ,business ,Chromosomes, Human, Pair 16 - Published
- 2020
41. Phase 1 Trial Evaluating Vorinostat Plus Bortezomib, Lenalidomide, and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma
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Charise Gleason, Roberto Mina, Jonathan L. Kaufman, Cathy Sharp, Jatin J. Shah, Leonard T. Heffner, Robert Z. Orlowski, Sagar Lonial, Jacob P. Laubach, Ajay K. Nooka, Paul G. Richardson, R. Donald Harvey, and Colleen Lewis
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Adult ,Male ,0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Inhibitor ,Myeloma ,Histone deacetylase ,Quadruplet induction ,Dexamethasone ,Bortezomib ,03 medical and health sciences ,0302 clinical medicine ,Maintenance therapy ,Internal medicine ,medicine ,Humans ,Adverse effect ,Lenalidomide ,Vorinostat ,Multiple myeloma ,Aged ,business.industry ,Hematology ,Middle Aged ,medicine.disease ,Transplantation ,030104 developmental biology ,030220 oncology & carcinogenesis ,Female ,Multiple Myeloma ,business ,medicine.drug - Abstract
Introduction Bortezomib plus lenalidomide and dexamethasone (VRD) is a standard induction therapy for newly diagnosed multiple myeloma (NDMM) patients. Given preclinical and clinical data suggesting the synergistic activity of the histone deacetylase inhibitor vorinostat with both bortezomib and lenalidomide for the treatment of multiple myeloma, we hypothesized that adding vorinostat to VRD (R2V2) would increase the rate and the quality of responses to induction treatment. Here we report the results of a phase 1 trial (NCT01038388) evaluating R2V2 as up-front treatment for NDMM patients. Patients and Methods R2V2 was tested as induction therapy in a dose-escalation phase 1 study in 30 NDMM patients deemed eligible for autologous stem-cell transplantation. Treatment consisted of 4 induction cycles with R2V2, followed by either autologous stem-cell transplantation or 4 additional R2V2 cycles and lenalidomide maintenance therapy. Results The maximum tolerated dose of vorinostat was 200 mg daily. The most common adverse events were gastrointestinal (87%), fatigue and peripheral neuropathy (60%), and thrombocytopenia (33%). R2V2 induced an objective response in 96% of patients, with 48% obtaining at least a complete remission. Median progression-free survival was 52 months, with 77% of patients alive at 5 years. Conclusion R2V2 as induction treatment for NDMM patients resulted in remarkable response rates at the cost of increased toxicity.
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- 2020
42. Therapeutic monoclonal antibodies and antibody products: Current practices and development in multiple myeloma
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Francesca Bonello, Roberto Mina, Mario Boccadoro, and Francesca Gay
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0301 basic medicine ,Cancer Research ,medicine.drug_class ,Bispecific T cell engagers (BiTEs®) ,medicine.medical_treatment ,T cell ,Review ,Monoclonal antibody ,03 medical and health sciences ,0302 clinical medicine ,Antigen ,B cell maturation antigens (BCMAs) ,medicine ,Cytotoxic T cell ,Elotuzumab ,Multiple myeloma (MM) ,Antibody products ,Immunotherapy ,Monoclonal antibodies (mAbs) ,biology ,business.industry ,Daratumumab ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,biology.protein ,Cancer research ,Antibody ,business ,medicine.drug - Abstract
Immunotherapy is the latest innovation for the treatment of multiple myeloma (MM). Monoclonal antibodies (mAbs) entered the clinical practice and are under evaluation in clinical trials. MAbs can target highly selective and specific antigens on the cell surface of MM cells causing cell death (CD38 and CS1), convey specific cytotoxic drugs (antibody-drug conjugates), remove the breaks of the immune system (programmed death 1 (PD-1) and PD-ligand 1/2 (L1/L2) axis), or boost it against myeloma cells (bi-specific mAbs and T cell engagers). Two mAbs have been approved for the treatment of MM: the anti-CD38 daratumumab for newly-diagnosed and relapsed/refractory patients and the anti-CS1 elotuzumab in the relapse setting. These compounds are under investigation in clinical trials to explore their synergy with other anti-MM regimens, both in the front-line and relapse settings. Other antibodies targeting various antigens are under evaluation. B cell maturation antigens (BCMAs), selectively expressed on plasma cells, emerged as a promising target and several compounds targeting it have been developed. Encouraging results have been reported with antibody drug conjugates (e.g., GSK2857916) and bispecific T cell engagers (BiTEs®), including AMG420, which re-directs T cell-mediated cytotoxicity against MM cells. Here, we present an overview on mAbs currently approved for the treatment of MM and promising compounds under investigation.
- Published
- 2020
43. CyTOF®: A New Tool to Decipher the Immunomodulatory Activity of Daratumumab
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Barbara Castella, Roberto Mina, and Francesca Gay
- Subjects
Histology ,medicine.drug_class ,business.industry ,immune profiling ,Antibody-Dependent Cell Cytotoxicity ,Antibodies, Monoclonal ,Daratumumab ,Original Articles ,Cell Biology ,cytometry by time of flight ,Monoclonal antibody ,medicine.disease ,Pathology and Forensic Medicine ,medicine ,Cancer research ,Humans ,DECIPHER ,Original Article ,CyTOF ,Multiple Myeloma ,business ,Multiple myeloma - Abstract
Daratumumab is a CD38‐targeted human monoclonal antibody with direct anti‐myeloma cell mechanisms of action. Flow cytometry in relapsed and/or refractory multiple myeloma (RRMM) patients treated with daratumumab revealed cytotoxic T‐cell expansion and reduction of immune‐suppressive populations, suggesting immune modulation as an additional mechanism of action. Here, we performed an in‐depth analysis of the effects of daratumumab on immune‐cell subpopulations using high‐dimensional mass cytometry. Whole‐blood and bone‐marrow baseline and on‐treatment samples from RRMM patients who participated in daratumumab monotherapy studies (SIRIUS and GEN501) were evaluated with high‐throughput immunophenotyping. In daratumumab‐treated patients, the intensity of CD38 marker expression decreased on many immune cells in SIRIUS whole‐blood samples. Natural killer (NK) cells were depleted with daratumumab, with remaining NK cells showing increased CD69 and CD127, decreased CD45RA, and trends for increased CD25, CD27, and CD137 and decreased granzyme B. Immune‐suppressive population depletion paralleled previous findings, and a newly observed reduction in CD38+ basophils was seen in patients who received monotherapy. After 2 months of daratumumab, the T‐cell population in whole‐blood samples from responders shifted to a CD8 prevalence with higher granzyme B positivity (P = 0.017), suggesting increased killing capacity and supporting monotherapy‐induced CD8+ T‐cell activation. High‐throughput cytometry immune profiling confirms and builds upon previous flow cytometry data, including comparable CD38 marker intensity on plasma cells, NK cells, monocytes, and B/T cells. Interestingly, a shift toward cytolytic granzyme B+ T cells was also observed and supports adaptive responses in patients that may contribute to depth of response. © 2018 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of International Society for Advancement of Cytometry.
- Published
- 2019
44. Real-World Patterns of Utilization and Outcome of Market Approved Lenalidomide-Based Triplet Combinations in First Relapsed Multiple Myeloma Patients: Evidence from a Propensity Score Matched Analysis
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Roberto Mina, Sara Pezzatti, Virginia Valeria Ferretti, Silvia Mangiacavalli, Angelo Belotti, Rita Mazza, Cecilia Olivares, Alessandra Pompa, Renato Zambello, Martina Soldarini, Laura Paris, Maria Teresa Petrucci, Francesca Farina, Francesca Fazio, Anna Maria Cafro, Gregorio Barilà, Magda Marcatti, Marica Lecci, Claudio Salvatore Cartia, Monica Galli, and Pietro Benvenuti
- Subjects
Oncology ,medicine.medical_specialty ,business.industry ,Immunology ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Outcome (game theory) ,Internal medicine ,Propensity score matching ,medicine ,business ,Multiple myeloma ,Lenalidomide ,medicine.drug - Abstract
Background: Lenalidomide (R) plus dexamethasone (d) triplet combinations have been indicated by ESMO guidelines as standard of care in first relapse for lenalidomide sensitive multiple myeloma (MM) patients (pts) (Dimopoulos et al, 2021). Meta-analysis of randomized clinical trials (RCT) shows better outcome with the combination of Daratumumab + Rd (DaraRd) over other Rd-based combinations (carfilzomib+Rd (KRd), elotuzumab+Rd (EloRd), Ixazomib+Rd (IxaRd). There are few real-life studies focusing on the pattern of utilization and outcome of different Rd triplets in first relapse MM. Aims: To explore performances of market-approved Rd-based triplets in unselected MM pts in first relapse. Patients and methods: After ethics committee approval, we review data of 366 MM pts in first relapse consecutively addressed to Rd-based triplets according to market-approved schedule after 2017. Rd-based therapies was distributed as follows: DaraRd 51.6% (189 pts), KRd 36.1% (132 pts), EloRd 8.7% (32 pts), IxaRd 3.6% (13 pts). Given the limited number of pts treated with IRd and EloRd, the analysis is focused only on DaraRd and KRd group after further excluding 51 pts (13%) addressed to salvage autologous stem cell transplant (ASCT) after daraRd (n=9)/KRd(n=42) fixed induction. Few pts in both groups were previously exposed to R/K/Dara (respectively 12 pts (3%), 8 (2%), 0). Treatment choice was influenced by market approval, with KRD regimen used more commonly in the IQR 2017- 2019, while DaraRd more commonly in the IQR 2018-2020. To limit the bias of a retrospective observation, we calculated a propensity score and we used it (after trimming of 5% of observations) to re-weight the data, according to the Inverse Probability of Treatment method (IPTW analysis). For the estimation of the propensity score, we used: age at Rd-triplet starting, ISS stage, presence of high-risk FISH, previous exposure to Bortezomib, previous ASCT, good response at first-line therapy (≥VGPR), time between diagnosis and relapse, myeloma defining events at diagnosis, type of relapse (symptomatic/biochemical), center. Details of these characteristics are reported in table1. Of note, pts addressed to DaraRd were slightly older (68,7 vs 63,4 years in KRd, p Conclusions: Our real-life study shows that DaraRd represents the most commonly received regimen at first relapse followed by KRd triplet. After propensity score matching, DaraRd and KRd combinations proved to be both effective with similar outcomes when used early in the treatment history, after one line of therapy. This study, in addition, points out the possible gap of outcome between RCT and clinical practice. Figure 1 Figure 1. Disclosures Mangiacavalli: BMS: Honoraria; Janssen: Honoraria; Takeda: Honoraria; GSK: Honoraria. Galli: BMS, Celgene, Janssen, Sanofi, Takeda: Honoraria. Belotti: Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy; GSK: Membership on an entity's Board of Directors or advisory committees. Fazio: Janseen: Honoraria. Petrucci: Celgene: Honoraria, Other: Advisory Board; Janssen-Cilag: Honoraria, Other: Advisory Board; BMS: Honoraria, Other: Advisory Board; Takeda: Honoraria, Other: Advisory Board; Amgen: Honoraria, Other: Advisory Board; GSK: Honoraria, Other: Advisory Board; Karyopharm: Honoraria, Other: Advisory Board.
- Published
- 2021
45. OAB-004: Carfilzomib-based induction/consolidation with or without autologous transplant and Lenalidomide (R) or Carfilzomib-Lenalidomide (KR) maintenance: efficacy in high-risk patients of the FORTE study
- Author
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Roberto Mina, Elena Zamagni, Delia Rota-Scalabrini, Paolo Corradini, Mariella Grasso, Stelvio Ballanti, Nicola Giuliani, Luca De Rosa, Claudia Cellini, Iolanda Donatella Vincelli, Cristina Velluti, Andrea Capra, Anna Maria Cafro, Alessandro Gozzetti, Massimo Gentile, Sara Aquino, Angelo Palmas, Antonio Ledda, Maria Teresa Petrucci, Pellegrino Musto, Mario Boccadoro, and Francesca Gay
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Cancer Research ,medicine.medical_specialty ,Double hit ,High risk patients ,MRD Negativity ,business.industry ,Hematology ,medicine.disease ,Carfilzomib ,Gastroenterology ,chemistry.chemical_compound ,Oncology ,chemistry ,Standard Risk ,Internal medicine ,medicine ,Autologous transplant ,business ,Multiple myeloma ,Lenalidomide ,medicine.drug - Abstract
Introduction Multiple myeloma (MM) patients (pts) with high-risk cytogenetic abnormalities (CA) have a shorter survival as compared to the standard-risk ones. In the FORTE study, carfilzomib-lenalidomide-dexamethasone induction/consolidation with ASCT (KRd-ASCT) significantly improved progression-free survival (PFS) vs KRd without ASCT (KRd12) or carfilzomib-cyclophosphamide-dexamethasone (KCd) plus ASCT (KCd-ASCT). KR maintenance also prolonged PFS vs R. The primary aim of this analysis was to evaluate the impact of treatment on PFS and 1-year sustained MRD negativity (1y-MRD neg) rates according to pt cytogenetic risk. Methods Pts were randomized to KRd-ASCT vs KCd-ASCT vs KRd12 and, thereafter, to KR vs R maintenance. High risk (HiR) was defined as the presence of ≥1 HiR CA [del17p, t(4;14), t(14;16), del1p and 1q gain (3 copies) or amp1q (≥4 copies)], double hit (DH) as the presence of ≥2 HiR CA, standard risk (SR) as the absence of all evaluated HiR CA. Results 396 out of 474 enrolled pts with complete fluorescence in situ hybridization (FISH) data were included in the analysis: 243 HiR, 105 DH and 153 SR pts. Among HiR pts, 60 had del17p, 65 t(4;14), 20 t(14;16), 44 del1p, 126 1q gain and 49 amp1q. SR pts benefited from intensification with KRd-ASCT vs KRd12 (HR 0.47, p=0.05) and KCd-ASCT (HR 0.38, p=0.01), with a 4-year PFS of 80%, 67% and 57%, respectively. In HiR pts, KRd-ASCT improved PFS vs KRd12 (HR 0.6, p=0.04) and KCd-ASCT (HR 0.57, p=0.01), with a 4-year PFS of 62%, 45% and 45%, respectively. The advantage with KRd-ASCT vs KRd12 (HR 0.53, p=0.07) and KCd-ASCT (HR 0.49; p=0.03) was also observed in DH pts (4-year PFS 55%, 31% and 33%, respectively). Despite the limited number of patients in each subgroup, a trend towards a PFS benefit from KRd-ASCT vs KRd12 was observed in pts with del17p (HR 0.61, p=0.3), t(4;14) (HR 0.59, p=0.2) and 1q gain (HR 0.45, p=0.02). In pts with del1p, KRd-ASCT (HR 0.24, p=0.06) and KRd12 (HR 0.33, p=0.09) showed superiority over KCd-ASCT, while amp1q pts had the worst outcome regardless of treatment (KRd-ASCT vs KCd-ASCT, HR 1.16, p=0.73; KRd12 vs KCd-ASCT, HR 1.34, p=0.45). KR improved PFS vs R in SR (3-year PFS 90% vs 73%, HR 0.42, p=0.06), HiR (3-year PFS 69% vs 56%, HR 0.6, p=0.04) and DH pts (3-year PFS 67% vs 42%, HR 0.53, p=0.1). Despite the small subgroups, a beneficial trend with KR vs R was observed in pts with del17p (HR 0.59, p=0.37), t(4;14) (HR 0.59, p=0.3), 1q gain (HR 0.54, p=0.07) and del1p (HR 0.23, p=0.08), while amp1q pts showed the worst outcome and no benefit from KR vs R (HR 0.83, p=0.7). Conclusion KRd-ASCT and KR maintenance are highly effective in SR and also in HiR and DH pts, with impressive 4-year PFS from diagnosis (KRd-ASCT: HiR 62%, DH 55%) and 3-year PFS from maintenance (KR: HiR 69%, DH 67%), thus providing an effective option in HiR pts, who still represent an unmet medical need.
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- 2021
46. Efficacy and Safety of Ixazomib Induction and Maintenance in Newly Diagnosed Multiple Myeloma Patients According to the IMWG Frailty Score: A Post-Hoc Analysis of the EMN10-Unito Trial
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Claudia Cellini, Roberto Mina, Giovannino Ciccone, Vanessa Innao, Monica Galli, Michele Cavo, Claudia Priola, Andrea Capra, Mario Boccadoro, Sara Aquino, Alessandra Larocca, Giusy Cetani, Massimo Offidani, Mariella Grasso, Sara Bringhen, Gloria Margiotta Casaluci, Giovanni De Sabbata, and Stelvio Ballanti
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Oncology ,medicine.medical_specialty ,business.industry ,Immunology ,Cell Biology ,Hematology ,Newly diagnosed ,medicine.disease ,Biochemistry ,Ixazomib ,chemistry.chemical_compound ,chemistry ,Internal medicine ,Post-hoc analysis ,medicine ,business ,Multiple myeloma - Abstract
INTRODUCTION. Elderly patients (pts) with newly diagnosed multiple myeloma (NDMM) are a heterogeneous population. The IMWG frailty score stratifies pts ≥65 years into 3 categories (fit, intermediate-fit and frail), according to chronological age, comorbidities and functional abilities, with different prognosis. We previously reported results from the phase II EMN10-Unito study investigating 4 Ixazomib-based induction regimens followed by Ixazomib maintenance in elderly NDMM pts. Here we present a post-hoc analysis of safety and efficacy of ixazomib-based induction regimens and maintenance according to IMWG frailty score. METHODS. NDMM, transplant-ineligible pts ≥65 years were enrolled. Treatment consisted of 9 induction cycles of Ixazomib combined with dexamethasone (Id), Cyclophosphamide-dexamethasone (ICd), Thalidomide-dexamethasone (ITd) or Bendamustine-dexamethasone (IBd), followed by single-agent Ixazomib maintenance for up to 2 years. Pts were stratified into 3 groups (fit, intermediate-fit and frail) according to IMWG frailty score. The aim of this analysis was to evaluate the efficacy (TTP, PFS, PFS2 and OS) and safety of ixazomib-based induction regimens and single-agent ixazomib maintenance in the 3 patient subgroups. RESULTS. 171 pts were enrolled in the study and started treatment; of these, 75 (44%) were classified as fit, 53 (31%) as intermediate-fit and 43 (25%) as frail. As expected, the median age was higher in frail (79 years) as compared with fit (71 years) and intermediate-fit (76 years) pts, and a worse ECOG score (1-2) was reported in frail (67%) as compared with fit (46%) and intermediate-fit pts (46%). Frail pts were also more likely to have ISS 2-3 myeloma (82%) compared with fit (59%) and intermediate-fit (77%) ones. The median follow-up for the entire population was 27 months. The ORR and VGPR rates after the induction were similar in fit (71%; 42%), intermediate-fit (74%; 38%) and frail pts (76%; 40%), although fit (8%) and intermediate-fit (13%) pts were more likely to achieve a CR than frail ones (2%). No significant differences in median PFS were observed among fit (14.1 months; HR: 0.75, p=0.27), intermediate-fit (14.8, HR: 0.68, p=0.12) as compared to frail pts (12.2 months). The median PFS2 was significantly longer in fit (41.1, HR: 0.48; p=0.04) and intermediate-fit (35.6, HR: 0.47, p=0.03) in comparison with frail pts (28.6 months). OS was longer in fit pts (NR; HR: 0.36, p=0.02) and intermediate-fit (NR; HR: 0.58, p=0.15) as compared to frail ones (36.7 months). The rates of grade 3-4 adverse events (AEs) and grade 3-4 non-hematological AEs during the induction phase were higher in frail pts (47% / 37%) as compared to fit (28% / 24%) and intermediate-fit (32% / 26%) ones. Similarly, the risk of treatment discontinuation was higher in frail (21%) as compared to fit (11%) and intermediate-fit pts (9%). When comparing PFS with three- vs two-drug ixazomib-based induction, both fit (HR: 0.75) and intermediate-fit (HR: 0.69) pts benefited from the use a triplet over a doublet; whereas, no difference between three- and two-drug combinations was observed in frail pts (HR: 1.01). Overall, 102 pts (60%) completed the induction phase and proceeded to ixazomib maintenance: of these, 46 (45%) were fit, 35 (34%) intermediate-fit and 21 (21%) frail. The median PFS from start of maintenance in the overall population was 15 months, without significant differences in intermediate-fit (HR: 0.92) and frail (HR: 1.14) pts as compared to fit ones. Concerning the safety of ixazomib maintenance, grade 3-4 non-hematological AEs were infrequent, occurring in 15% of fit pts (15%), 3% of intermediate-fit and 5% of frail (5%) ones. Ixazomib dose reductions were more frequent in frail (24%) as compared to fit (13%) and intermediate-fit (11%) pts, although a similar percentage of pts discontinued ixazomib due to AEs in the three groups (fit: 11%; intermediate-fit: 15%; frail: 10%). CONCLUSIONS. Ixazomib-based regimens had similar efficacy in terms of ORR and PFS, irrespective of frailty status, although AEs, dose modifications and treatment discontinuation were more frequent in frail pts. Importantly, frail pts did not seem to benefit from the addition of a third drug over the use of a doublet induction therapy. Single-agent ixazomib maintenance was effective and well tolerated in fit, as well as in intermediate-fit and frail pts, thus representing an appealing maintenance option in elderly MM. Disclosures Mina: Takeda: Honoraria; Celgene: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria. Larocca:Amgen: Honoraria; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Honoraria; Takeda: Membership on an entity's Board of Directors or advisory committees. Offidani:Celgene: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Galli:BMS: Honoraria; Celgene: Honoraria; Janssen: Honoraria; Takeda: Honoraria. De Sabbata:Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees. Cavo:Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel accomodations, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Karyopharm: Honoraria; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel accomodations, Speakers Bureau; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Boccadoro:Mundipharma: Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Research Funding; AbbVie: Honoraria; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Bringhen:Bristol-Myers Squibb: Honoraria; Takeda: Consultancy; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: The presentation includes discussion of off-label use of a drug or drugs for the treatment of multiple myeloma (including ixazomib, dexamethasone, cyclophosphamide, thalidomide and bendamustine).
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- 2020
47. Ixazomib-Based Induction Followed By Single-Agent Ixazomib Maintenance in Transplant Ineligible, Newly Diagnosed Multiple Myeloma Patients: Updated Results of the EMN10-Unito Trial
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Anna Baraldi, Giovannino Ciccone, Renato Zambello, Angelo Belotti, Michele Cea, Delia Rota Scalabrini, Norbert Pescosta, Francesca Patriarca, Roberto Mina, Annalisa Bernardini, Mario Boccadoro, Sara Bringhen, Nicola Cascavilla, Anna Marina Liberati, Francesca Fazio, Alessandra Larocca, Paolo Corradini, and Andrea Capra
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Oncology ,medicine.medical_specialty ,business.industry ,Immunology ,Cell Biology ,Hematology ,Newly diagnosed ,medicine.disease ,Biochemistry ,Transplant ineligible ,Ixazomib ,chemistry.chemical_compound ,chemistry ,Internal medicine ,Medicine ,Single agent ,business ,Multiple myeloma - Abstract
INTRODUCTION. The proteasome inhibitor (PI) Ixazomib, approved for the treatment of relapsed/refractory multiple myeloma (MM), represents an appealing option for the management of elderly patients, due to its oral administration and the lack of peripheral neuropathy. We previously presented preliminary results of the phase II EMN10-Unito study investigating Ixazomib in combination with dexamethasone (Id), Cyclophosphamide-dexamethasone (ICd), Thalidomide-dexamethasone (ITd) or Bendamustine-dexamethasone (IBd) as induction therapy followed by single-agent Ixazomib maintenance in transplant-ineligible newly diagnosed (ND) MM patients. Here we present updated results of the study with a longer follow-up. METHODS. Transplant-ineligible NDMM patients ≥65 years were enrolled. Treatment consisted of 9 28-day induction cycles of Ixazomib 4 mg on days 1,8,15 and dexamethasone 40 mg on days 1,8,15,22 or Id plus either Cyclophosphamide 300 mg/m2 orally on days 1,8,15 or Thalidomide 100 mg/day or Bendamustine 75 mg/m2 iv on days 1,8; followed by Ixazomib maintenance (4 mg on days 1,8,15) for up to 2 years. The primary endpoint was the selection of the most effective induction regimen considering a 2-year progression-free survival (PFS) ≥65% as satisfactory; secondary endpoints were very good partial response (VGPR), PFS2, overall survival (OS) and adverse events (AEs) during induction and maintenance. RESULTS. 171 patients (Id 41, ICd 59, ITd 60 and IBd 11) with a median age of 74 years were enrolled and started treatment. Two of the four investigational arms were prematurely closed due to low-enrollment (IBd arm, 11 patients enrolled) and high risk of inefficacy (Id, 41 patients enrolled). Median follow-up was 27 months. After the induction phase, ICd and ITd resulted in higher ≥ PR (75%-84% vs. 57%; p Overall, 102 patients (60%) completed the induction phase and proceeded to ixazomib maintenance (median follow-up from start of maintenance: 18 months). The best response during maintenance was PR in 26%, VGPR in 29%, and complete response (CR) in 26% of patients; 18% of patients improved the response obtained during induction by at least one IMWG category. The median PFS from start of maintenance was 15 months. The median duration of maintenance was 12 months. All grades AEs occurred in 39% of patients during maintenance, while grade 3-4 AEs occurred in 10% of patients. Grade 1-2 peripheral neuropathy (PN) was reported in 15% of patients, without grade 3-4 events. Overall, 15% required at least one dose reduction of ixazomib and 12% discontinued ixazomib maintenance due to AEs. CONCLUSIONS. Safety and efficacy data suggest that Id combined with cyclophosphamide was the most promising induction strategy compared to the other investigated combinations. Continuous treatment with single-agent Ixazomib confirmed its efficacy and tolerability in elderly NDMM patients. Disclosures Mina: Amgen: Honoraria; Celgene: Honoraria; Takeda: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Larocca:GSK: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Takeda: Membership on an entity's Board of Directors or advisory committees. Corradini:KiowaKirin: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Other: Travel and accommodations paid by for; Sanofi: Consultancy, Honoraria; Servier: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Other; BMS: Other; Kite: Consultancy, Honoraria; Gilead: Consultancy, Honoraria, Other: Travel and accommodations paid by for; Daiichi Sankyo: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Other: Travel and accommodations paid by for; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Other: Travel and accommodations paid by for; Incyte: Consultancy; Celgene: Consultancy, Honoraria, Other: Travel and accommodations paid by for; F. Hoffman-La Roche Ltd: Consultancy, Honoraria. Liberati:CELGENE: Honoraria; BIOPHARMA: Honoraria; ARCHIGEN: Honoraria; BEIGENE: Honoraria; BMS: Honoraria; AMGEN: Honoraria; FIBROGEN: Honoraria; INCYTE: Honoraria; VERASTEM: Honoraria, Research Funding; ROCHE: Honoraria, Research Funding; PFIZER: Honoraria, Research Funding; ONCOPEPTIDES AB: Honoraria, Research Funding; TAKEDA: Honoraria, Research Funding; MORPHOSYS: Honoraria, Research Funding; ONCONOVA: Honoraria, Research Funding; ABBVIE: Honoraria, Research Funding; NOVARTIS: Honoraria, Research Funding; KARYOPHARM: Honoraria, Research Funding; JANSSEN: Honoraria. Zambello:Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees. Belotti:Amgen: Membership on an entity's Board of Directors or advisory committees; Jannsen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Boccadoro:Sanofi: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; AbbVie: Honoraria; Mundipharma: Research Funding; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees. Bringhen:Takeda: Consultancy; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: The presentation includes discussion of off-label use of a drug or drugs for the treatment of multiple myeloma (including ixazomib, dexamethasone, cyclophosphamide, thalidomide and bendamustine).
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- 2020
48. On-Demand Plerixafor with Cyclophosphamide and G-CSF for Hematopoietic Stem-Cell Mobilization in Multiple Myeloma Patients: Preliminary Results of a Prospective Observational Study (MOZOBL06877)
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Giusy Cetani, Mario Boccadoro, Daniele Derudas, Andrea Capra, Delia Rota Scalabrini, Maria Teresa Petrucci, Alessandra Malfitano, Paolo Corradini, Michele Cavo, Roberto Mina, Pellegrino Musto, Massimo Offidani, Velia Bongarzoni, Giuseppe Milone, Francesco Pisani, Chiara Nozzoli, Tommaso Caravita di Toritto, Roberto M. Lemoli, Francesca Bonello, Alessandra Larocca, Stelvio Ballanti, and Patrizia Tosi
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Oncology ,medicine.medical_specialty ,Cyclophosphamide ,business.industry ,Plerixafor ,education ,Immunology ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Internal medicine ,On demand ,Medicine ,Observational study ,business ,health care economics and organizations ,Hematopoietic Stem Cell Mobilization ,Multiple myeloma ,medicine.drug - Abstract
Background. High-dose melphalan followed by autologous stem cell transplantation is a standard of care in transplant-eligible newly diagnosed multiple myeloma (NDMM) patients and is also an option at relapse. Therefore, since the minimum number of CD34+ cells required to ensure adequate bone marrow recovery after myeloablative chemotherapy is 2x10^6/kg, an adequate upfront stem-cell collection is necessary in MM patients. Approximately 5-15% of MM patients mobilized with granulocyte colony-stimulating factor (G-CSF) or G-CSF+cyclophosphamide (G-CSF/CY) fail stem-cell collection ( Methods. NDMM patients undergoing stem-cell mobilization with cyclophosphamide (2-4 g/m2) and G-CSF (5-10 mcg/kg/day), with on-demand plerixafor according to clinical practice ( Results. At the data cut-off (09 June 2020), a total of 252 patients had been enrolled: of these, 192 patients (59, 29-72 years) were available for the analysis. The median number of induction cycles before mobilization was 4 (range 1-7); median time from diagnosis to mobilization was 6 months (IQR 5-8). Induction therapy consisted of a bortezomib-based regimen in 171 (90%), carfilzomib/lenalidomide-based regimen in 14 (7%), lenalidomide-based regimen in 3 patients (2%). 187/192 (97%) patients successfully collected ≥2 x 10^6/Kg CD34: of these, 153/192 (80%) collected with G-CSF/CY, 29/192 (15%) required the administration of plerixafor. The PM rate was 5/192 (2.5%): of these, 3/5 did not receive plerixafor in addition to G-CSF/CY, while 2/5 failed stem-cell collection despite the use of plerixafor. The median number of CD34 collected was 9.8x10^6/Kg (6.7-14.2). The median number of CD34/Kg collected with or without plerixafor was 5.1 (4.3-9.1) and 10.6 (8.1-14.4), respectively. The median number of apheresis days was 1 (IQR 1-2), with a stem-cell collection efficiency (CD34 number collected/ days of apheresis) equal to 7.7 x10^6 CD34/kg/day. The median number of apheresis days was 1 without plerixafor and 2 with plerixafor, with a stem-cell collection efficiency (CD34 number collected/ days of apheresis) equal to 8.8 without plerixafor and 3 with plerixafor. In patients who received plerixafor, the median number of CD34/ul pre-apheresis was 16 (10-19.5); after the administration of plerixafor, the median number of CD34/ul pre-apheresis increased to 46 (21-81). Non hematological AEs within 30 days after mobilization occurred in 8% of patients (grade 3-4: 2%); all grade and grade 3-4 infections occurred in 2% of patients each. In a multivariate analysis, main factors predicting the use of plerixafor were ISS 3 (vs. 1, OR 4.43; p=0.008), bone marrow plasma cells at diagnosis >60% (OR 3.85; p=0.006), white blood cell (WBC) count pre-mobilization (OR 6.66; p Conclusion. "On-demand" plerixafor combined with G-CSF/CY is a safe and effective rescue strategy for stem-cell collection in MM, reducing the PM rate to 2.5%. Extensive bone marrow plasmacytosis, ISS 3 disease at diagnosis, use of lenalidomide during induction and a low WBC count pre-mobilization predicted the use of plerixafor. Thus, pre-emptive administration of plerixafor in patients presenting one or more risk factors for poor mobilization might help in further reducing the PM rate. Disclosures Mina: Amgen: Honoraria; Celgene: Honoraria; Takeda: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Petrucci:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees. Lemoli:AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; BerGenBio ASA: Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Jazz: Consultancy, Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees; Servier: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding. Offidani:BMS: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Musto:Amgen: Honoraria; Celgene: Honoraria. Corradini:F. Hoffman-La Roche Ltd: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Other: Travel and accommodations paid by for; Celgene: Consultancy, Honoraria, Other: Travel and accommodations paid by for; Daiichi Sankyo: Consultancy, Honoraria; Incyte: Consultancy; Novartis: Consultancy, Honoraria, Other: Travel and accommodations paid by for; Janssen: Consultancy, Honoraria; Gilead: Consultancy, Honoraria, Other: Travel and accommodations paid by for; KiowaKirin: Consultancy, Honoraria; Servier: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Other; BMS: Other; Sanofi: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Other: Travel and accommodations paid by for; Kite: Consultancy, Honoraria. Cavo:BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel accomodations, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel accomodations, Speakers Bureau; GlaxoSmithKline: Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Karyopharm: Honoraria. Boccadoro:GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding; AbbVie: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Research Funding; Mundipharma: Research Funding; Novartis: Honoraria, Research Funding; Amgen: Honoraria, Research Funding. Larocca:Takeda: Membership on an entity's Board of Directors or advisory committees; GSK: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria. OffLabel Disclosure: The presentation includes discussion of off-label use of a drug or drugs for the treatment of patients with multiple myeloma (including cyclophosphamide, G-CSF and plerixafor).
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- 2020
49. Carfilzomib-based induction/consolidation with or without autologous transplant (ASCT) followed by lenalidomide (R) or carfilzomib-lenalidomide (KR) maintenance: Efficacy in high-risk patients
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Francesca Gay, Roberto Mina, Delia Rota-Scalabrini, Monica Galli, Angelo Belotti, Elena Zamagni, Luca Bertamini, Renato Zambello, Barbara Gamberi, Giovanni De Sabbata, Giuseppe Pietrantuono, Andrea Capra, Anna Pascarella, Anna Marina Liberati, Salvatore Palmieri, Angela Cuoghi, Massimo Offidani, Michele Cavo, Pellegrino Musto, and Mario Boccadoro
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Oncology ,Cancer Research ,medicine.medical_specialty ,High risk patients ,business.industry ,medicine.disease ,Carfilzomib ,chemistry.chemical_compound ,chemistry ,Internal medicine ,medicine ,Autologous transplant ,business ,Multiple myeloma ,Lenalidomide ,medicine.drug - Abstract
8002 Background: Cytogenetic abnormalities (CA) are one of the most powerful prognostic factors in multiple myeloma (MM). In the FORTE study, carfilzomib-lenalidomide-dexamethasone induction/consolidation with ASCT (KRd_ASCT) significantly improved progression-free survival (PFS) vs KRd without ASCT (KRd12, HR 0.64) or carfilzomib-cyclophosphamide-dexamethasone (KCd) plus ASCT (KCd_ASCT, HR 0.53). KR maintenance significantly improved PFS vs R (HR 0.63). Methods: MM patients (pts) were randomized to KRd_ASCT vs KCd_ASCT vs KRd12 and, thereafter, to KR vs R maintenance. Subgroup analyses according to FISH evaluated the impact of each single high-risk (HiR) CA [del17p, t(4;14), t(14;16), del1p and 1q gain (3 copies) or amp1q (≥4 copies)] and that of combined CA, defining HiR by the presence of ≥1 HiR CA and double-hit (DH) by the presence of ≥2 HiR CA. Pts negative for all the HiR CA were considered at standard risk (SR). The primary objective was the impact of treatment on PFS according to pt risk. Results: 396 out of 474 enrolled pts were included in the analysis with complete FISH data: 243 HiR, 105 DH and 153 SR. Among HiR pts, 60 had del17p, 65 t(4;14), 20 t(14;16), 44 del1p, 126 1q gain and 49 amp1q. SR pts benefited from intensification with KRd_ASCT vs KRd12 (HR 0.47, p = 0.05) and KCd_ASCT (HR 0.38, p = 0.01), with a 4-year PFS of 80%, 67% and 57%, respectively. In HiR pts, KRd_ASCT improved PFS vs KRd12 (HR 0.6, p = 0.04) and KCd_ASCT (HR 0.57, p = 0.01), with a 4-year PFS of 62%, 45% and 45%, respectively. The advantage with KRd_ASCT vs KRd12 (HR 0.53, p = 0.07) and KCd_ASCT (HR 0.49; p = 0.03) was also observed in DH pts (4-year PFS 55%, 31% and 33%, respectively). Analyses by single CA were limited by the small number of pts in each subgroup, but a trend towards a PFS benefit from KRd_ASCT vs KRd12 was seen in pts with del17p (HR 0.61, p = 0.3), t(4;14) (HR 0.59, p = 0.2) and 1q gain (HR 0.45, p = 0.02). In pts with del1p, KRd_ASCT (HR 0.24, p = 0.06) and KRd12 (HR 0.33, p = 0.09) showed superiority over KCd_ASCT, while amp1q pts had the worst outcome regardless of treatment (KRd_ASCT vs KCd_ASCT, HR 1.16, p = 0.73; KRd12 vs KCd_ASCT, HR 1.34, p = 0.45). KR improved PFS vs R in SR (3-year PFS 90% vs 73%, HR 0.42, p = 0.06), HiR (3-year PFS 69% vs 56%, HR 0.6, p = 0.04) and DH pts (3-year PFS 67% vs 42%, HR 0.53, p = 0.1). Despite the small subgroups, a beneficial trend with KR vs R was observed in pts with del17p (HR 0.59, p = 0.37), t(4;14) (HR 0.59, p = 0.3), 1q gain (HR 0.54, p = 0.07) and del1p (HR 0.23, p = 0.08), while amp1q pts showed the worst outcome and no benefit from KR vs R (HR 0.83, p = 0.7). Conclusions: KRd_ASCT and KR maintenance are highly effective in SR and also in HiR and DH pts, with impressive 4-year PFS from diagnosis (KRd_ASCT: HiR 62%, DH 55%) and 3-year PFS from maintenance (KR: HiR 69%, DH 67%), thus supporting their use in HiR pts, who represent an unmet medical need. Clinical trial information: NCT02203643.
- Published
- 2021
50. Emerging drugs and combinations to treat multiple myeloma
- Author
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Alessandra Larocca, Roberto Mina, Francesca Gay, Sara Bringhen, and Mario Boccadoro
- Subjects
Oncology ,medicine.medical_specialty ,medicine.drug_class ,Novel agents ,Review ,Monoclonal antibodies ,Multiple myeloma ,Pharmacology ,Monoclonal antibody ,Ixazomib ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,immune system diseases ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Lenalidomide ,Bortezomib ,business.industry ,medicine.disease ,Pomalidomide ,Carfilzomib ,chemistry ,030220 oncology & carcinogenesis ,Proteasome inhibitor ,business ,030215 immunology ,medicine.drug - Abstract
In the past few years, multiple targeted therapies and immunotherapies including second generation immunomodulatory drugs (pomalidomide) and proteasome inhibitors (carfilzomib, ixazomib), monoclonal antibodies and checkpoint inhibitors were approved for the treatment of myeloma or entered advanced phases of clinical testing. These agents showed significant activity in advanced myeloma and increased the available treatment strategies. Pomalidomide is well-tolerated and effective in patients with relapsed/refractory multiple myeloma who have exhausted any possible treatment with lenalidomide and bortezomib. Carfilzomib, a second-generation proteasome inhibitor, is active as a single agent and in combination with other anti-myeloma agents. Ixazomib is the first oral proteasome inhibitor to be evaluated in myeloma and is associated with a good safety profile and anti-myeloma activity in relapsed/refractory patients, even in those refractory to bortezomib. Monoclonal antibodies and immune checkpoint inhibitors are likely to play a major role in the treatment of myeloma over the next decade. In phase 3 studies, triplet regimens based on these agents combined with a backbone therapy (including lenalidomide, pomalidomide or bortezomib) were more efficacious than doublet regimens in patients with relapsed/refractory multiple myeloma, with limited additional toxic effects. This paper aims to provide an overview of the recent use of these agents for the treatment of myeloma, in particular focusing on the role of multi-agent combinations.
- Published
- 2017
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