0000000000134703
AUTHOR
Enrica Antonia Martino
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.
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 real-life 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%…
Adjusted comparison between elotuzumab and carfilzomib in combination with lenalidomide and dexamethasone as salvage therapy for multiple myeloma patients
The lack of a randomized trial comparing carfilzomib (K) versus elotuzumab (Elo) associated with lenalidomide and dexamethasone (Rd) prompted us to assess the relative usefulness of one triplet over the other. Five independent retrospective cohorts of 883 relapsed/refractory multiple myeloma (RRMM) patients, including 300 EloRd and 583 KRd cases, outside clinical trials, entered this non-randomized comparison. KRd cohort accounted for a higher incidence of younger patients, cases with ≥3 lines of therapy, already exposed to lenalidomide, International Staging System (ISS) stage III, and abnormal lactic dehydrogenase (LDH) level compared with EloRd cohort. Moreover, cytogenetic risk categori…
Mechanisms of Immune Evasion in Multiple Myeloma: Open Questions and Therapeutic Opportunities
Simple Summary The growing interest in immunotherapy for the treatment of multiple myeloma demands a deep knowledge of the complex interactions between malignant and immune cells within the bone marrow. Indeed, understanding the cellular and molecular mechanisms underlying this network should represent the basis for the design of novel patient-oriented biological therapeutic approaches. Here, we describe the role of the main immune components of the myeloma niche along disease evolution and their implication in impairing/improving the response to anti-cancer treatments. Additionally, we provided an overview of the potential weakness of this pro-tumor interplay, evidencing novel therapeutic …
Eltrombopag treatment for severe immune thrombocytopenia during pregnancy: a case report
Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by isolated thrombocytopenia (platelet count <100 × 109/l) in the absence of other causes or disorders associated. The incidence of ITP in pregnancy is one to two cases per 1000 gestations. ITP could be diagnosed before or during pregnancy; sometimes a relapse of a previously diagnosed ITP can occur. Intravenous immune globulins (IVIg) and corticosteroids are the standard frontline therapy because of their well known safety profile either for the mother or for the neonate. Treatments for refractory patients are limited by potential fetal risk. We report the case of a patient with ITP along pregnancy, refractory…
Assessment of the 4-factor score: Retrospective analysis of 586 CLL patients receiving ibrutinib. A campus CLL study
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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.
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 &lt; 0.0001), older age (HR = 1.72; P &lt; 0.0001), and prior lenalidomide exposure (…
Feasibility, Tolerability and Efficacy of Carfilzomib in Combination with Lenalidomide and Dexamethasone in Relapsed Refractory Myeloma Patients: A Retrospective Real-Life Survey of the Sicilian Myeloma Network
Background: The ASPIRE (NCT01080391) phase 3 trial showed the efficacy of carfilzomib, lenalidomide and dexamethasone (KRd) triplet for relapse and refractory multiple myeloma (RRMM). However, little is known about safety and efficacy of KRd outside a clinical trial context. Methods: Herein we report real life results of KRd given to 130 RRMM patients from 12 Sicilian Centers. Results: Median age was 62 years
Elotuzumab plus lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: Extended 3‐year follow‐up of a multicenter, retrospective clinical experience with 319 cases outside of controlled clinical trials
: The combination of elotuzumab, lenalidomide, and dexamethasone (EloRd) enhanced the clinical benefit over Rd with a manageable toxicity profile in the ELOQUENT-2 trial, leading to its approval in relapsed/refractory multiple myeloma (RRMM). The present study is a 3-year follow-up update of a previously published Italian real-life RRMM cohort of patients treated with EloRd. This revised analysis entered 319 RRMM patients accrued in 41 Italian centers. After a median follow-up of 36 months (range 6-55), 236 patients experienced disease progression or died. Median progression-free survival (PFS) and overall survival (OS) were 18.4 and 34 months, respectively. The updated multivariate analyse…
Impact of Cumulative Dose of Carfilzomib in Combination with Lenalidomide and Dexamethasone in Relapsed Refractory Myeloma Patients: A Retrospective Real Life Survey of the Sicilian Myeloma Network
Abstract Background: Triplet-based lenalidomide plus dexamethasone (Rd) combinations have become the new standard of care for early relapse and refractory multiple myeloma (RRMM). Carfilzomib is a novel selective proteasome inhibitor (PI) with high efficacy in RRMM. The ASPIRE phase 3 trial showed the superiority of carfilzomib-based triplet (KRd compared to Rd), leading to approval of K for RRMM. However, little is known about safety and efficacy of KRd outside a clinical trial context. Experimental design and aims: In 11 Sicilian Centers belonging to the Sicilian Myeloma Network, from November 2016, when KRd regimen was approved in Italy, to June 2018, 103 consecutive RRMM patients (previ…
Treatment of Lenalidomide Exposed or Refractory Multiple Myeloma: Network Meta-Analysis of Lenalidomide-Sparing Regimens.
Over the past 10 years, the treatment of multiple myeloma (MM) dramatically changed due to the introduction of a number of new agents and combination regimens both in the frontline and in the relapsed/refractory setting. Currently, at least 11 classes of therapeutic agents, including steroids, alkylators (melphalan and cyclophosphamide), proteasome inhibitors (PI: bortezomib, carfilzomib, ixazomib), immunomodulatory agents (thalidomide, lenalidomide, pomalidomide), monoclonal antibodies (mAbs: elotuzumab, daratumumab), HDAC-inhibitors (panobinostat), BCL2 inhibitors (venetoclax), selective inhibitors of nuclear export (selinexor), drug-conjugated mAbs (belantamab mafodotin), bispecific agen…