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Article ; Online: An open-label phase 2 study treating patients with first or second relapse of multiple myeloma with carfilzomib, pomalidomide, and dexamethasone (KPd): SELECT study.

Perrot, Aurore / Delimpasi, Sosana / Spanoudakis, Emmanouil / Frølund, Ulf / Belotti, Angelo / Oriol, Albert / Moreau, Philippe / McFadden, Ian / Xia, Qing / Arora, Mukta / Dimopoulos, Meletios Athanasios

Leukemia & lymphoma

2024 , Page(s) 1–10

Abstract: Once-weekly carfilzomib at 56 mg/ ... ...

Abstract	Once-weekly carfilzomib at 56 mg/m
Language	English
Publishing date	2024-03-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	1042374-6
ISSN	1029-2403 ; 1042-8194
ISSN (online)	1029-2403
ISSN	1042-8194
DOI	10.1080/10428194.2024.2322030
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Article ; Online: Predictive role of sustained imaging MRD negativity assessed by diffusion-weighted whole-body MRI in multiple myeloma.

Belotti, Angelo / Ribolla, Rossella / Crippa, Claudia / Chiarini, Marco / Giustini, Viviana / Ferrari, Samantha / Peli, Annalisa / Cattaneo, Chiara / Roccaro, Aldo / Frittoli, Barbara / Grazioli, Luigi / Rossi, Giuseppe / Tucci, Alessandra

American journal of hematology

2023 Volume 98, Issue 9, Page(s) E230–E232

MeSH term(s)	Humans ; Multiple Myeloma/diagnostic imaging ; Multiple Myeloma/therapy ; Diffusion Magnetic Resonance Imaging/methods ; Neoplasm, Residual
Language	English
Publishing date	2023-06-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	196767-8
ISSN	1096-8652 ; 0361-8609
ISSN (online)	1096-8652
ISSN	0361-8609
DOI	10.1002/ajh.26995
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Article ; Online: COVID-19 does not impact on outcome of myeloma patients infected while undergoing autologous stem cell transplantation.

Masina, Lorenzo / Bianchetti, Nicola / Passi, Angela / Bottelli, Chiara / Bagnasco, Samuele / Spolzino, Angelica / Oberti, Margherita / Chiarini, Marco / Belotti, Angelo / Voltolini, Simone / Faglioni, Laura / Rossi, Giuseppe / Tucci, Alessandra / Cattaneo, Chiara

Hematological oncology

2023 Volume 41, Issue 3, Page(s) 555–558

Abstract: Here we report two cases of myeloma patients who became positive for SARS-CoV-2 infection during the acute phase of autologous stem cell transplant. Both patients were promptly treated with monoclonal antibodies and remdesivir, and, despite the profound ... ...

Abstract	Here we report two cases of myeloma patients who became positive for SARS-CoV-2 infection during the acute phase of autologous stem cell transplant. Both patients were promptly treated with monoclonal antibodies and remdesivir, and, despite the profound neutropenia and lymphopenia, they did not develop respiratory failure and they remained paucisymptomatic during the entire period of aplasia. Neutrophil engraftment took place as expected and the patients were discharged quickly and did not experience adverse effects after discharge.
MeSH term(s)	Humans ; Multiple Myeloma/complications ; Multiple Myeloma/therapy ; Hematopoietic Stem Cell Transplantation ; COVID-19/complications ; SARS-CoV-2 ; Transplantation, Autologous
Language	English
Publishing date	2023-02-17
Publishing country	England
Document type	Case Reports
ZDB-ID	604884-5
ISSN	1099-1069 ; 0278-0232
ISSN (online)	1099-1069
ISSN	0278-0232
DOI	10.1002/hon.3127
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Article: RR Myelo POINT: A Retrospective Single-Center Study Assessing the Role of Radiotherapy in the Management of Multiple Myeloma and Possible Interactions with Concurrent Systemic Treatment.

Cancers

2022 Volume 14, Issue 9

Abstract: Background and purpose: Although chemotherapy, biological agents, and radiotherapy (RT) are cornerstones of the treatment of multiple myeloma (MM), the literature regarding the possible interactions of concurrent systemic treatment (CST) and RT is ... ...

Abstract	Background and purpose: Although chemotherapy, biological agents, and radiotherapy (RT) are cornerstones of the treatment of multiple myeloma (MM), the literature regarding the possible interactions of concurrent systemic treatment (CST) and RT is limited, and the optimal RT dose is still unclear. Materials and methods: We retrospectively analyzed the records of patients who underwent RT for MM at our institution from 1 January 2005 to 30 June 2020. The data of 312 patients and 577 lesions (treated in 411 accesses) were retrieved. Results: Most of the treated lesions involved the vertebrae (60%) or extremities (18.9%). Radiotherapy was completed in 96.6% of the accesses and, although biologically effective doses assuming an α/β ratio of 10 (BED 10) > 38 Gy and CST were significantly associated with higher rates of toxicity, the safety profile was excellent, with side effects grade ≥2 reported only for 4.1% of the accesses; CST and BED 10 had no impact on the toxicity at one and three months. Radiotherapy resulted in significant improvements in performance status and in a pain control rate of 87.4% at the end of treatment, which further increased to 96.9% at three months and remained at 94% at six months. The radiological response rate at six months (data available for 181 lesions) was 79%, with only 4.4% of lesions in progression. Progression was significantly more frequent in the lesions treated without CST or BED 10 < 15 Gy, while concurrent biological therapy resulted in significantly lower rates of progression. Conclusion: Radiotherapy resulted in optimal pain control rates and fair toxicity, regardless of BED 10 and CST; the treatments with higher BED 10 and CST (remarkably biological agents) improved the already excellent radiological disease control.
Language	English
Publishing date	2022-05-02
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14092273
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Article ; Online: A real-world retrospective-prospective analysis of efficacy and safety of combined ixazomib, lenalidomide, and dexamethasone in relapsed/refractory multiple myeloma: The northern Italy experience.

Furlan, Anna / Cea, Michele / Pavan, Laura / Galli, Monica / Clissa, Cristina / Mangiacavalli, Silvia / Cafro, Anna Maria / Girlanda, Stefania / Patriarca, Francesca / Minotto, Claudia / Bertoldero, Giovanni / Barilà, Gregorio / Pascarella, Anna / Lico, Albana / Paolini, Rossella / Rabassi, Nicholas / Pescosta, Norbert / Porrazzo, Marika / De Sabbata, Giovanni /

Pompa, Alessandra / Bega, Giulia / Cavallin, Stefania / Guidotti, Francesca / Marcatti, Magda / Rupolo, Maurizio / Belotti, Angelo / Gherlinzoni, Filippo / Zambello, Renato

Cancer medicine

2024 Volume 13, Issue 7, Page(s) e7071

Abstract: Introduction: Ixazomib, lenalidomide, and dexamethasone (IRd) have been approved for the treatment of relapsed/refractory multiple myeloma (RRMM) based on the results of the TOURMALINE-MM1.: Objectives and methods: We conducted a retrospective- ... ...

Abstract	Introduction: Ixazomib, lenalidomide, and dexamethasone (IRd) have been approved for the treatment of relapsed/refractory multiple myeloma (RRMM) based on the results of the TOURMALINE-MM1. Objectives and methods: We conducted a retrospective-prospective analysis of 106 RRMM patients (pts) treated with IRd in 21 centers in Northern Italy, with the aim to evaluate the efficacy and safety of IRd in real life. Results: At IRd initiation, 34% of pts were aged ≥75 (median 72.5), 8.5% had an ECOG performance status ≥2, 54.7% of evaluable pts carried high-risk cytogenetic abnormalities [del17p and/or t(4;14) and/or t(14;16) and/or 1 g gain/amp], 60.2% had received ≥2 prior lines of therapy (pLoT), 57.5% were lenalidomide (Len)-exposed (including both Len-sensitive and Len-refractory pts), and 22% were Len-refractory. Main G ≥3 adverse events (AEs) were thrombocytopenia (16%) and neutropenia (12.3%). G ≥3 non-hematologic AEs included infections (9.4%) and GI toxicity (diarrhea 5.7%, hepatotoxicity 2.8%), VTE, skin rash, and peripheral neuropathy were mainly G1-2. The overall response rate was 56.4% (≥VGPR 30%). With a median follow-up of 38 m, median PFS (mPFS) was 16 m and the 1-year OS rate was 73%. By subgroup analysis, an extended PFS was observed for pts achieving ≥VGPR (mPFS 21.2 m), time from diagnosis to IRd ≥5 years (26.2 m), 1 pLoT (34.4 m), Len-naïve (NR), age ≥70 (20 m). In pts exposed to Len, non-refractory in any prior line and immediately prior to IRd, mPFS was 16 and 18 m, respectively. An inferior PFS was seen in Len-refractory pts (4.6 m). By multivariate analysis, independent predictors of PFS were age ≥70 (HR 0.6), time from diagnosis ≥5 years (HR 0.32), refractoriness to Len in any prior line (HR 3.33), and immediately prior (HR 4.31). Conclusion: IRd might be effective and safe in RRMM pts with an indolent disease, in early lines of treatment, and who proved Len-sensitive, independent of age, and cytogenetic risk.
MeSH term(s)	Humans ; Lenalidomide/adverse effects ; Multiple Myeloma/drug therapy ; Multiple Myeloma/etiology ; Retrospective Studies ; Dexamethasone ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Boron Compounds ; Glycine/analogs & derivatives
Chemical Substances	Lenalidomide (F0P408N6V4) ; ixazomib (71050168A2) ; Dexamethasone (7S5I7G3JQL) ; Boron Compounds ; Glycine (TE7660XO1C)
Language	English
Publishing date	2024-04-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	2659751-2
ISSN	2045-7634 ; 2045-7634
ISSN (online)	2045-7634
ISSN	2045-7634
DOI	10.1002/cam4.7071
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Article ; Online: The role of clonal hematopoiesis as driver of therapy-related myeloid neoplasms after autologous stem cell transplantation.

Gramegna, Doriana / Bertoli, Diego / Cattaneo, Chiara / Almici, Camillo / Re, Alessandro / Belotti, Angelo / Borlenghi, Erika / Lanzi, Gaetana / Archetti, Silvana / Verardi, Rosanna / Brugnoni, Duilio / Sciumè, Margherita / Daffini, Rosa / Roccaro, Aldo M / Tucci, Alessandra / Rossi, Giuseppe

Annals of hematology

2022 Volume 101, Issue 6, Page(s) 1227–1237

Abstract: Therapy-related myeloid neoplasm (t-MN) is a threatening complication of autologous stem cell transplantation (ASCT). Detecting clonal hematopoiesis (CH) mutations in cryopreserved cells before ASCT has been associated with a higher risk of t-MN, but the ...

Abstract	Therapy-related myeloid neoplasm (t-MN) is a threatening complication of autologous stem cell transplantation (ASCT). Detecting clonal hematopoiesis (CH) mutations in cryopreserved cells before ASCT has been associated with a higher risk of t-MN, but the evolution of molecular abnormalities from pre-ASCT to t-MN, within the same patient, remains to be elucidated. We evaluated the mutational profile of 19 lymphoma/myeloma patients, at both pre-ASCT and t-MN diagnosis, using a targeted NGS approach; 26 non-developing t-MN control patients were also studied pre-ASCT. At ASCT, we found a higher frequency of CH in patients developing t-MN (58%) than in those who did not (23%) (P = 0.029); mutations in epigenetic (DNMT3A, TET2, and ASXL1) and DNA repair genes (PPM1D, RAD21, TP53, and STAG2) were the most represented. At t-MN, CH increased to 82% of patients. Cumulative mutational burden and variant allele frequency (VAF) also increased at t-MN. CH clones detected at ASCT were found at t-MN in eight out of 16 patients, mainly with stable VAF. Among the new driver mutations appeared at t-MN, TP53 increased from one to 13 mutations, in nine patients; being associated with complex karyotype. Mutations in transcription factor (RUNX1, CEBPA) and intracellular signaling genes (FLT3, RAS genes) also increased from three to 17 mutations in eight patients, presenting with a normal karyotype. Overall, we found that preexisting CH at ASCT rarely causes t-MN directly, but may rather facilitate the appearance of new mutations, especially those involving TP53, RUNX1, and RAS, that can drive the evolution to t-MN of at least two distinct types.
MeSH term(s)	Clonal Hematopoiesis/genetics ; Core Binding Factor Alpha 2 Subunit/genetics ; Hematopoiesis/genetics ; Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Mutation ; Myeloproliferative Disorders/complications ; Myeloproliferative Disorders/genetics ; Myeloproliferative Disorders/therapy ; Neoplasms, Second Primary/genetics ; Transplantation, Autologous/adverse effects
Chemical Substances	Core Binding Factor Alpha 2 Subunit
Language	English
Publishing date	2022-04-05
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1064950-5
ISSN	1432-0584 ; 0939-5555 ; 0945-8077
ISSN (online)	1432-0584
ISSN	0939-5555 ; 0945-8077
DOI	10.1007/s00277-022-04806-x
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Article ; Online: Prospective evaluation of minimal residual disease in the phase II FORTE trial: a head-to-head comparison between multiparameter flow cytometry and next-generation sequencing.

Oliva, Stefania / Genuardi, Elisa / Paris, Laura / D'Agostino, Mattia / Rogers, Jennifer / Rota-Scalabrini, Delia / Jacob, Allison P / Patriarca, Francesca / Luppi, Mario / Bertazzoni, Paola / Velluti, Cristina / Capra, Andrea / Saraci, Elona / Rossi, Marco / Allegra, Alessandro / Mina, Roberto / Gentile, Massimo / Kirsch, Ilan R / Belotti, Angelo /

Cavo, Michele / Bruno, Benedetto / Musto, Pellegrino / Boccadoro, Mario / Zamagni, Elena / Gay, Francesca

EClinicalMedicine

2023 Volume 60, Page(s) 102016

Abstract: Background: Limited data are available on the concordance between multiparameter flow cytometry (MFC) and next-generation sequencing (NGS) for minimal residual disease (MRD) detection in a large trial for multiple myeloma (MM) patients.: Methods: MRD ...

Abstract	Background: Limited data are available on the concordance between multiparameter flow cytometry (MFC) and next-generation sequencing (NGS) for minimal residual disease (MRD) detection in a large trial for multiple myeloma (MM) patients. Methods: MRD was explored in the FORTE trial for transplant-eligible MM patients randomised to three carfilzomib-based induction-intensification-consolidation treatments and carfilzomib-lenalidomide (KR) Findings: Between September 28, 2015 and December 22, 2021, 2020 samples were available for MFC and 728 for the simultaneous MFC/NGS correlation in the "suspected CR population". Median follow-up was 62 months. Biological agreement was 87% at the 10 Interpretation: The significant biological/clinical concordance between MFC and NGS at the same sensitivity suggests their possible use in the evaluation of one of the currently strongest predictors of outcome. Funding: Amgen, Celgene/Bristol Myers Squibb, Multiple Myeloma Research Foundation.
Language	English
Publishing date	2023-06-09
Publishing country	England
Document type	Journal Article
ISSN	2589-5370
ISSN (online)	2589-5370
DOI	10.1016/j.eclinm.2023.102016
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Article ; Online: Lenalidomide-based triplet regimens in first relapsed multiple myeloma patients: real-world evidence from a propensity score matched analysis.

Mangiacavalli, Silvia / Cartia, Claudio Salvatore / Galli, Monica / Pezzatti, Sara / Belotti, Angelo / Fazio, Francesca / Mina, Roberto / Marcatti, Magda / Cafro, Anna / Zambello, Renato / Paris, Laura / Barilà, Gregorio / Olivares, Cecilia / Pompa, Alessandra / Mazza, Rita / Farina, Francesca / Soldarini, Martina / Benvenuti, Pietro / Pagani, Giuseppina /

Palumbo, Michele / Masoni, Valeria / Ferretti, Virginia Valeria / Klersy, Catherine / Arcaini, Luca / Petrucci, Maria Teresa

Haematologica

2023 Volume 108, Issue 3, Page(s) 833–842

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 ... ...

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<0.001). With the limitations of any retrospective analysis, our real-life PSM comparison between DaraRd and KRd, in first-relapse MM patients, showed better tolerability and prolonged PFS of DaraRd, although with some gaps of performance, in particular of DaraRd, with respect to RCT. Carfilzomib-containing regimens, like KRd, still remain a valid second-line option in the emerging scenario of first-line daratumumab-based therapy.
MeSH term(s)	Humans ; Multiple Myeloma/drug therapy ; Lenalidomide/therapeutic use ; Propensity Score ; Neoplasm Recurrence, Local/drug therapy ; Dexamethasone/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/adverse effects
Chemical Substances	Lenalidomide (F0P408N6V4) ; Dexamethasone (7S5I7G3JQL)
Language	English
Publishing date	2023-03-01
Publishing country	Italy
Document type	Meta-Analysis ; Journal Article
ZDB-ID	2333-4
ISSN	1592-8721 ; 0017-6567 ; 0390-6078
ISSN (online)	1592-8721
ISSN	0017-6567 ; 0390-6078
DOI	10.3324/haematol.2022.281342
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Article ; Online: Predictors of unsustained measurable residual disease negativity in patients with multiple myeloma.

D'Agostino, Mattia / Bertuglia, Giuseppe / Rota-Scalabrini, Delia / Belotti, Angelo / Morè, Sonia / Corradini, Paolo / Oliva, Stefania / Ledda, Antonio / Grasso, Mariella / Pavone, Vincenzo / Ronconi, Sonia / Vincelli, Iolanda Donatella / Ballanti, Stelvio / Velluti, Cristina / Cellini, Claudia / Gozzetti, Alessandro / Palmas, Angelo D / Gamberi, Barbara / Mancuso, Katia /

Paris, Laura / Zambello, Renato / Petrucci, Maria Teresa / Bruno, Benedetto / Musto, Pellegrino / Gay, Francesca

Blood

2023 Volume 143, Issue 7, Page(s) 592–596

Abstract: Abstract: The prognostic impact of achieving and in particular maintaining measurable residual disease (MRD) negativity in multiple myeloma is now established; therefore, identifying among MRD-negative patients the ones at higher risk of losing MRD ... ...

Abstract	Abstract: The prognostic impact of achieving and in particular maintaining measurable residual disease (MRD) negativity in multiple myeloma is now established; therefore, identifying among MRD-negative patients the ones at higher risk of losing MRD negativity is of importance. We analyzed predictors of unsustained MRD negativity in patients enrolled in the FORTE trial (NCT02203643). MRD was performed by multiparameter flow cytometry (sensitivity of 10-5) at premaintenance and every 6 months thereafter. The cumulative incidence (CI) of MRD resurgence and/or progression was analyzed in MRD-negative patients. A total of 306 of 474 (65%) MRD-negative patients were analyzed. After a median follow-up of 50.4 months from MRD negativity, 185 of 306 (60%) patients were still MRD negative and progression free, 118 (39%) lost their MRD-negative status, and 3 patients (1%) died without progression. Amp1q vs normal (4-year CI, 63% vs 34), ≥2 concomitant high-risk cytogenetic abnormalities vs 0 (4-year CI, 59% vs 33%), circulating tumor cells at baseline (high vs low at 4-year CI, 62% vs 32%), and time-to-reach MRD negativity postconsolidation vs preconsolidation (4-year CI, 46% vs 35%) were associated with a higher risk of unsustained MRD negativity in a multivariate Fine-Gray model. During the first 2 years of maintenance, patients receiving carfilzomib-lenalidomide vs lenalidomide alone had a lower risk of unsustained MRD negativity (4-year CI, 20% vs 33%).
MeSH term(s)	Humans ; Multiple Myeloma/drug therapy ; Lenalidomide/therapeutic use ; Treatment Outcome ; Neoplasm, Residual ; Prognosis
Chemical Substances	Lenalidomide (F0P408N6V4)
Language	English
Publishing date	2023-12-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood.2023022080
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Article ; Online: Incidental whole-body MRI evidence of COVID-19 in an asymptomatic patient in a high prevalence region

Angelini, Valentina / Villanacci, Alberta / Belotti, Angelo / Castagnoli, Francesca / Frittoli, Barbara / Corvino, Antonio / Brunetti, Arturo / Grazioli, Luigi

Egyptian Journal of Radiology and Nuclear Medicine

2020 Volume 51, Issue 1

Abstract: Abstract Background The purpose of this case report is to emphasize the importance of curing any clinical radiological elements in this historical period, especially in the area of endemic to coronavirus disease 19 (COVID-19) such as Lombardy and to ... ...

Abstract	Abstract Background The purpose of this case report is to emphasize the importance of curing any clinical radiological elements in this historical period, especially in the area of endemic to coronavirus disease 19 (COVID-19) such as Lombardy and to stress the importance of the management of the asymptomatic patient, their crucial role in the spread of contagion. Case presentation We reported the case of incidental diagnosis of interstitial pneumonia by first finding on whole-body MR (WB-MR) in the patient affected by multiple myeloma (MM), with a negative respiratory symptoms at the time and with previous (1 month before) negative chest X-ray. The patient was promptly subjected to chest CT, which confirmed the suspicion of interstitial COVID-19 pneumonia and, in hospitalization, performed nasopharyngeal swabs for real-time polymerase chain reaction (RNA-PCR), with a doubtful outcome. Once the bacterial nature of the alterations was serologically and radiologically excluded, the patient was definitively diagnosed with COVID-19 and appropriately treated in hospitalization. Conclusion The clinical choices must, therefore, to make use of all the diagnostic tools available and full knowledge of the limitation of each of them.
Keywords	covid19
Language	English
Publisher	Springer Science and Business Media LLC
Publishing country	us
Document type	Article ; Online
ZDB-ID	2583928-7
ISSN	2090-4762 ; 0378-603X
ISSN (online)	2090-4762
ISSN	0378-603X
DOI	10.1186/s43055-020-00288-x
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