Adjusted comparison between elotuzumab and carfilzomib in combination with lenalidomide and dexamethasone as salvage therapy for multiple myeloma patients

Morabito, Fortunato; Zamagni, Elena; Conticello, Concetta; Pavone, Vincenzo; Palmieri, Salvatore; Bringhen, Sara; Galli, Mónica; Mangiacavalli, Silvia; Derudas, Daniele; Rossi, Elena; Ria, Roberto; Catalano, Lucio; Tacchetti, Paola; Mele, Giuseppe; Vincelli, Iolanda Donatella; Martino, Enrica Antonia; Vigna, Ernesto; Botta, Cirino; Bruzzese, Antonella; Mele, Anna; Pantani, Lucia; Rocchi, Serena; Garibaldi, Bruno; Cascavilla, Nicola; Ballanti, Stelvio; Tripepi, Giovanni; Frigeri, Ferdinando; Falcone, A.; Cangialosi, Clotilde; Reddiconto, Giovanni; Farina, G.; Barone, Marialucia; Rizzello, Ilaria; Musto, Pellegrino; Stefano, Valerio De; Musso, Maurizio; Petrucci, Maria Teresa; Offidani, Massimo; Neri, Antonino; Renzo, Nicola Di; Raimondo, Francesco Di; Boccadoro, Mario; Cavo, Michèle; Gentile, Massimo

doi:10.1111/ejh.13723

Cited by 7 publications

(11 citation statements)

References 33 publications

(57 reference statements)

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“…Roughly one‐quarter of cases presented unfavorable cytogenetic abnormalities, harboring one of the following aberrations: t(4; 14), t(14; 16), and del(17p). The median number of previous therapies was 2 1–11 . Approximately 50% of the patients received KRd as second‐line treatment; 36.3% of the population was exposed to lenalidomide.…”

Section: Resultsmentioning

confidence: 99%

Carfilzomib combined with lenalidomide and dexamethasone (KRd) as salvage therapy for multiple myeloma patients: italian, multicenter, retrospective clinical experience with 600 cases outside of controlled clinical trials

Martino

Conticello

Zamagni

et al. 2022

Hematological Oncology

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In combination with lenalidomide and dexamethasone (KRd), Carfilzomib has been approved for the treatment of relapsed and refractory multiple myeloma (RRMM) on ASPIRE trial. Efficacy and safety of the triplet are still the object of investigation by many groups to confirm ASPIRE results in the setting of RRMM treated in reallife who don't meet trial restrictive inclusion criteria. Therefore, we report a retrospective multicenter analysis of 600 RRMM patients treated with KRd between December 2015 and December 2018. The median age was 64 years (range 33-85), and the median number of previous therapies was two (range 1-11). After a median of 11 KRd cycles, the overall response rate was 79.9%. The median progression-free survival (PFS) was 22 months, and the 2-year probability of PFS was 47.6%. Creatinine clearance<30 ml/min, >1 line of previous therapy, and highrisk FISH were all associated with a poor prognosis in multivariate analysis. The median overall survival (OS) was 34.8 months; the 2-year probability of OS was 63.5%. At multivariate analysis, creatinine clearance<30 ml/min, >1 line of previous therapy, and high-risk FISH were significantly associated with poor prognosis. After a median follow-up of 16 months (range 1-50), 259 withdrew from therapy. The main discontinuation reason was progressive disease (81.8%). Seventy-four patients (12.3%) discontinued therapy for toxicity. The most frequent side effects were hematological (anemia 49.3%, neutropenia 42.7%, thrombocytopenia 42.5%) and cardiovascular (hypertension 14.5%, heart failure 2.5%, arrhythmias 3.6%). Our study confirms the safety and efficacy of KRd in the real-life setting of RRMM patients and encourages its use in clinical practice.

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Section: Resultsmentioning

confidence: 99%

Carfilzomib combined with lenalidomide and dexamethasone (KRd) as salvage therapy for multiple myeloma patients: italian, multicenter, retrospective clinical experience with 600 cases outside of controlled clinical trials

Martino

Conticello

Zamagni

et al. 2022

Hematological Oncology

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“…Utilizing the above detailed prognostic models, we derived a survival risk score for OS (SRS KRd/EloRd ) and PFS (PRS KRd/EloRd ). The regression coefficient in predicting mortality ( 29 , 30 ) has been used to assign weights to variables independently associated with death or progression/death. The calculations of death and progression/death risk scores to be assigned on an individual basis are described in Supplementary Tables 1 , 2 , respectively.…”

Section: Resultsmentioning

confidence: 99%

“…EloRd and KRd patients were treated according to marketing approval ( 29 ). The refractoriness designates disease in patients who achieve a minor response (MR) or better and either become non-responsive while undergoing salvage therapy or who progress within 60 days of the last treatment ( 30 ).…”

Section: Methodsmentioning

confidence: 99%

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Survival Risk Scores for Real-Life Relapsed/Refractory Multiple Myeloma Patients Receiving Elotuzumab or Carfilzomib In Combination With Lenalidomide and Dexamethasone as Salvage Therapy: Analysis of 919 Cases Outside Clinical Trials

et al. 2022

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The present study aimed to develop two survival risk scores (RS) for overall survival (OS, SRSKRd/EloRd) and progression-free survival (PFS, PRSKRd/EloRd) in 919 relapsed/refractory multiple myeloma (RRMM) patients who received carfilzomib, lenalidomide, and dexamethasone (KRd)/elotuzumab, lenalidomide, and dexamethasone (EloRd). The median OS was 35.4 months, with no significant difference between the KRd arm versus the EloRd arm. In the multivariate analysis, advanced ISS (HR = 1.31; P = 0.025), interval diagnosis–therapy (HR = 1.46; P = 0.001), number of previous lines of therapies (HR = 1.96; P < 0.0001), older age (HR = 1.72; P < 0.0001), and prior lenalidomide exposure (HR = 1.30; P = 0.026) remained independently associated with death. The median PFS was 20.3 months, with no difference between the two strategies. The multivariate model identified a significant progression/death risk increase for ISS III (HR = 1.37; P = 0.002), >3 previous lines of therapies (HR = 1.67; P < 0.0001), older age (HR = 1.64; P < 0.0001), and prior lenalidomide exposure (HR = 1.35; P = 0.003). Three risk SRSKRd/EloRd categories were generated: low-risk (134 cases, 16.5%), intermediate-risk (467 cases, 57.3%), and high-risk categories (213 cases, 26.2%). The 1- and 2-year OS probability rates were 92.3% and 83.8% for the low-risk (HR = 1, reference category), 81.1% and 60.6% (HR = 2.73; P < 0.0001) for the intermediate-risk, and 65.5% and 42.5% (HR = 4.91; P < 0.0001) for the high-risk groups, respectively. Notably, unlike the low-risk group, which did not cross the median timeline, the OS median values were 36.6 and 18.6 months for the intermediate- and high-risk cases, respectively. Similarly, three PRSKRd/EloRd risk categories were engendered. Based on such grouping, 338 (41.5%) cases were allocated in the low-, 248 (30.5%) in the intermediate-, and 228 (28.0%) in the high-risk groups. The 1- and 2-year PFS probability rates were 71.4% and 54.5% for the low-risk (HR = 1, reference category), 68.9% and 43.7% (HR = 1.95; P < 0.0001) for the intermediate-risk, and 48.0% and 27.1% (HR = 3.73; P < 0.0001) for the high-risk groups, respectively. The PFS median values were 29.0, 21.0, and 11.7 months for the low-, intermediate-, and high-risk cases. This analysis showed 2.7- and 4.9-fold increased risk of death for the intermediate- and high-risk cases treated with KRd/EloRd as salvage therapy. The combined progression/death risks of the two categories were increased 1.3- and 2.2-fold compared to the low-risk group. In conclusion, SRSKRd/EloRd and PRSKRd/EloRd may represent accessible and globally applicable models in daily clinical practice and ultimately represent a prognostic tool for RRMM patients who received KRd or EloRd.

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“…Nowadays, there are growing experiences confirming the efficacy of KRd salvage regimen when used in daily practice. (18,19,38) Collection of data regarding anti-CD38 MoAb Daratumumab are more limited, often focusing on its use as single agent in more advance RRMM patients. (39,40) The few RWD on DaraRd found gaps in terms of response rate and PFS with respect to POLLUX trial, largely attributed to higher rate of baseline adverse prognostic factors like multiple comorbidities, advanced disease phases, lenalidomide refractoriness.…”

Section: Discussionmentioning

confidence: 99%

Lenalidomide-based triplet regimens in first relapsed multiple myeloma patients: real-world evidence from a propensity score matched analysis

Mangiacavalli¹,

Cartia²,

Galli³

et al. 2022

haematol

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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 the 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 vs 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 better tolerated, registering a lower rate of grade 3-4 non-hematological toxicity (OR: 0.4, p

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Adjusted comparison between elotuzumab and carfilzomib in combination with lenalidomide and dexamethasone as salvage therapy for multiple myeloma patients

Cited by 7 publications

References 33 publications

Carfilzomib combined with lenalidomide and dexamethasone (KRd) as salvage therapy for multiple myeloma patients: italian, multicenter, retrospective clinical experience with 600 cases outside of controlled clinical trials

Carfilzomib combined with lenalidomide and dexamethasone (KRd) as salvage therapy for multiple myeloma patients: italian, multicenter, retrospective clinical experience with 600 cases outside of controlled clinical trials

Survival Risk Scores for Real-Life Relapsed/Refractory Multiple Myeloma Patients Receiving Elotuzumab or Carfilzomib In Combination With Lenalidomide and Dexamethasone as Salvage Therapy: Analysis of 919 Cases Outside Clinical Trials

Lenalidomide-based triplet regimens in first relapsed multiple myeloma patients: real-world evidence from a propensity score matched analysis

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