Real-World (RW) Multiple Myeloma (MM) Patients (Pts) Remain Under-Represented in Clinical Trials Based on Standard Laboratory Parameters and Baseline Characteristics: Analysis of over 3,000 Pts from the Insight MM Global, Prospective, Observational Study

Hungria, Vânia; Lee, Hans C.; Abonour, Rafat; Rifkin, Robert M.; Terpos, Evangelos; Leleu, Xavier; Costello, Caitlin; Rhee, Frits van; Weisel, Katja; Puig, Noemí; Berdeja, Jesús G.; Cook, Gordon; Usmani, Saad Z.; Thompson, Michael A.; Boccadoro, Mario; Zonder, Jeffrey A.; Spencer, Andrew; Fanning, Suzanne R.; Boyd, Kevin; Omel, Jim; Armour, Mira; Morgan, Kathryn E.; Patel, Ronak S.; Carlson, Gary; Ferrari, Renda H.; Stull, Dawn Marie; Ren, Kaili; Cherepanov, Dasha; Pottala, James V.; Chari, Ajai

doi:10.1182/blood-2019-125749

Cited by 13 publications

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“…It has been reported that 40% of patients enrolled in the CONNECT-MM registry (ClinicalTrials.gov: NCT01081028) do not meet standard eligibility criteria for randomized trials [3]. Similarly, an analysis of over 3000 patients enrolled in the INSIGHT MM global, prospective, observational study (NCT02761187) showed that 39% of MM patients treated in routine clinical practice would be ineligible for trials [4]. Furthermore, a retrospective analysis of a US electronic health record database demonstrated that 47.9 to 72.3% of real-world patients with relapsed/refractory MM (RRMM) did not meet the eligibility criteria for clinical trials [5].…”

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Ixazomib-Lenalidomide-Dexamethasone in Routine Clinical Practice: Effectiveness in Relapsed/refractory Multiple Myeloma

et al. 2021

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Aim: To evaluate the effectiveness and safety of ixazomib-lenalidomide-dexamethasone (IRd) in relapsed/refractory multiple myeloma in routine clinical practice. Patients & methods: Patient-level data from the global, observational INSIGHT MM and the Czech Registry of Monoclonal Gammopathies were integrated and analyzed. Results: At data cut-off, 263 patients from 13 countries were included. Median time from diagnosis to start of IRd was 35.8 months; median duration of follow-up was 14.8 months. Overall response rate was 73%, median progression-free survival, 21.2 months and time-to-next therapy, 33.0 months. Ixazomib/lenalidomide dose reductions were required in 17%/36% of patients; 32%/30% of patients discontinued ixazomib/lenalidomide due to adverse events. Conclusion: The effectiveness and safety of IRd in routine clinical practice are comparable to those reported in TOURMALINE-MM1. Clinical trial registration: NCT02761187 (ClinicalTrials.gov)

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confidence: 99%

Ixazomib-Lenalidomide-Dexamethasone in Routine Clinical Practice: Effectiveness in Relapsed/refractory Multiple Myeloma

et al. 2021

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“…The population for the ongoing US MM-6 study includes patients from the community who might not be eligible for clinical trials because of factors that could impact their ability to respond to and/ or tolerate treatment, such as older age, poor performance status, advanced disease stage, prevalent comorbidities, and laboratory abnormalities (which could indicate neutropenia, thrombocytopenia, anemia, hypercalcemia, or poor renal or hepatic function). 8,14,15,30 Renal impairment is a common presenting feature in patients with NDMM, and patients with renal impairment have been underrepresented in randomized clinical trials owing to exclusion criteria that include the creatinine clearance level. 15 Several of the enrollment criteria used in US MM-6 allow for inclusion of a broader patient population compared with the criteria used in standard clinical trials (eg, all creatinine clearance levels were permitted, a history of previous malignancies > 2 years previously was permitted, and iCT was permitted for patients achieving only stable disease after bortezomib-based induction therapy).…”

Section: Discussionmentioning

confidence: 99%

“…8,14,15,30 Renal impairment is a common presenting feature in patients with NDMM, and patients with renal impairment have been underrepresented in randomized clinical trials owing to exclusion criteria that include the creatinine clearance level. 15 Several of the enrollment criteria used in US MM-6 allow for inclusion of a broader patient population compared with the criteria used in standard clinical trials (eg, all creatinine clearance levels were permitted, a history of previous malignancies > 2 years previously was permitted, and iCT was permitted for patients achieving only stable disease after bortezomib-based induction therapy). Furthermore, the study was designed to enroll patients solely from community centers and to allow the centers to follow their own usual standard-of-care procedures for the selection of first-line bortezomib-based induction therapy and patient evaluation and management.…”

Section: Discussionmentioning

confidence: 99%

“…Evaluation of patient-level data from the US-based Connect-MM registry and other analyses of real-world MM populations have shown that 22% to 73% of patients with MM would be ineligible to participate in randomized controlled trials. 8,14,15,30 Consequently, efforts are ongoing to broaden the clinical trial inclusion criteria, where possible, 7,31 with studies such as US MM-6 designed to ensure generalizability of the results to patients who will be receiving anti-MM treatments in everyday practice. To date, in the US MM-6 study, the median age is 73 years, with nearly one half of the patients aged !…”

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confidence: 99%

“…7 Analyses have shown that up to 40% of real-world patients with NDMM would be ineligible for participation in clinical trials. 8,14,15 Given that extended treatment with PI-based therapy has resulted in improved outcomes in clinical trials, 5 we believed it would be valuable to conduct a study to assess the potential benefit of continuous, long-term PI-based treatment in a US community setting. A novel approach to facilitate long-term PI-based treatment in routine clinical practice would be to use an in-class transition (iCT) from a parenteral (bortezomib) to an oral (ixazomib) PI.…”

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confidence: 99%

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Feasibility of Long-term Proteasome Inhibition in Multiple Myeloma by in-class Transition From Bortezomib to Ixazomib

Manda¹,

Yimer²,

Noga³

et al. 2020

Clinical Lymphoma Myeloma and Leukemia

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Although long-term proteasome inhibitor therapy improves outcomes in multiple myeloma, many patients cannot tolerate long-term treatment or might require or prefer to continue treatment outside the hospital or clinic. The US MM-6 study is evaluating the in-class transition from parenteral bortezomib-to oral ixazomibbased therapy in routine clinical practice. Preliminary results indicate feasibility, prolonged therapy duration, promising efficacy, and treatment adherence and satisfaction. Background: The ongoing US MM-6 study is investigating in-class transition (iCT) from parenteral bortezomibbased induction to all-oral IRd (ixazomib-lenalidomide-dexamethasone) with the aim of increasing proteasome inhibitor (PI)-based treatment adherence and duration while maintaining patients' health-related quality of life (HRQoL) and improving outcomes. Patients and Methods: US community sites are enrolling nonetransplanteligible patients with newly diagnosed multiple myeloma (MM) with no evidence of progressive disease after 3 cycles of bortezomib-based therapy to receive IRd (up to 39 cycles or until progression or toxicity). The patients use mobile or wearable digital devices to collect actigraphy (activity and sleep) data and electronically complete HRQoL, treatment satisfaction and medication adherence questionnaires. The primary endpoint is progressionfree survival. The key secondary endpoints include response rates and therapy duration. Results: At the data cutoff, 84 patients had been treated (median age 73 years; 44% aged ! 75 years; 49% men; 15% Black or African American; and 10% Hispanic or Latino). Of the 84 patients, 62% were continuing therapy. The mean duration of total PI therapy was 10.1 months and for the IRd regimen was 7.3 months. With an 8-month median follow-up, the 12-month progression-free survival rate was 86% (95% confidence interval, 73%-93%) from both the start of bortezomib-based treatment and the start of IRd. The overall response rate was 62% (complete response, 4%; very good partial response, 25%; partial response, 33%) after bortezomib-based induction and 70% (complete response, 26%; very good partial response, 29%; partial response, 15%) after iCT. The IRd safety profile was consistent with previous clinical trial data, and HRQoL and treatment satisfaction were maintained. Conclusion:

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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,

Cea,

Pavan

et al. 2024

Cancer Medicine

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IntroductionIxazomib, 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 MethodsWe 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.ResultsAt 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).ConclusionIRd 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.

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Real-World (RW) Multiple Myeloma (MM) Patients (Pts) Remain Under-Represented in Clinical Trials Based on Standard Laboratory Parameters and Baseline Characteristics: Analysis of over 3,000 Pts from the Insight MM Global, Prospective, Observational Study

Cited by 13 publications

References 0 publications

Ixazomib-Lenalidomide-Dexamethasone in Routine Clinical Practice: Effectiveness in Relapsed/refractory Multiple Myeloma

Ixazomib-Lenalidomide-Dexamethasone in Routine Clinical Practice: Effectiveness in Relapsed/refractory Multiple Myeloma

Feasibility of Long-term Proteasome Inhibition in Multiple Myeloma by in-class Transition From Bortezomib to Ixazomib

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

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