Real-world treatment patterns and associated progression-free survival in relapsed/refractory multiple myeloma among US community oncology practices

Jagannath, Sundar; Roy, Anuja; Kish, Jonathan; Lunacsek, Orsolya; Eaddy, Michael; Kuriakose, Emil; Willey, Joanne; Butler-Bird, Stephanie; Siegel, David S.

doi:10.1080/17474086.2016.1195254

Cited by 39 publications

(33 citation statements)

References 15 publications

(25 reference statements)

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“…17,19,32,33 Furthermore, in the real-world clinical practice setting, early discontinuations due to toxicities are common. 34 As long-term, continuous therapy is associated with improved outcomes, 9–13 a tolerable, more convenient treatment regimen suitable for long-term use is needed, especially in elderly patients.…”

Section: Discussionmentioning

confidence: 99%

A phase I/II dose-escalation study investigating all-oral ixazomib-melphalan-prednisone induction followed by single-agent ixazomib maintenance in transplant-ineligible newly diagnosed multiple myeloma

et al. 2018

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This phase I/II dose-escalation study investigated the all-oral ixazomib-melphalan-prednisone regimen, followed by single-agent ixazomib maintenance, in elderly, transplant-ineligible patients with newly diagnosed multiple myeloma. Primary phase I objectives were to determine the safety and recommended phase II dose of ixazomib-melphalan-prednisone. The primary phase II objective was to determine the complete plus very good partial response rate. In phase I, patients were enrolled to 4 arms investigating weekly or twice-weekly ixazomib (13 28-day cycles or nine 42-day cycles) plus melphalan-prednisone. In phase II, an expansion cohort was enrolled at the recommended phase II ixazomib dose. Of the 61 patients enrolled, 26 received the recommended phase II dose (ixazomib 4.0 mg [days 1, 8, 15] plus melphalan-prednisone 60 mg/m2 [days 1-4], 28-day cycles). Of the 61 enrolled patients, 36 (13 of 26 in the recommended phase II dose cohort) received single-agent ixazomib maintenance (days 1, 8, 15; 28-day cycles). In phase I, 10/38 patients reported dose-limiting toxicities in cycle 1, including grade 3 and/or 4 neutropenia (n=6) and thrombocytopenia (n=4). Complete plus very good partial response rate was 48% (48% at recommended phase II dose), including 28% (22%) complete response or better; responses deepened during maintenance in 34% (33%) of evaluable patients. After median follow up of 43.6 months, median progression-free survival was 22.1 months. Adverse events were mainly hematologic events, gastrointestinal events, and peripheral neuropathy. This study demonstrates the feasibility, tolerability, and activity of ixazomib-melphalan-prednisone induction and single-agent ixazomib maintenance in transplant-ineligible newly diagnosed multiple myeloma patients. clinicaltrials.gov identifier 01335685.

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Section: Discussionmentioning

confidence: 99%

A phase I/II dose-escalation study investigating all-oral ixazomib-melphalan-prednisone induction followed by single-agent ixazomib maintenance in transplant-ineligible newly diagnosed multiple myeloma

et al. 2018

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“…Despite available treatments, studies have shown that the depth of response decreases with each additional line of therapy [30][31][32]. MM remains incurable with patients continuously relapsing over time, and is associated with significant patient burden.…”

Section: Targeting Cd38 In MMmentioning

confidence: 99%

Therapeutic Opportunities with Pharmacological Inhibition of CD38 with Isatuximab

Martin

Corzo

Chiron

et al. 2019

Cells

114

151

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CD38 is a transmembrane glycoprotein with ectoenzymatic activity involved in regulation of migration, signal transduction, and receptor-mediated adhesion. CD38 is highly expressed on various malignant cells, including multiple myeloma (MM), and at relatively low levels in other tissues, making it a suitable target for therapeutic antibodies. Several anti-CD38 therapies have been, or are being, developed for the treatment of MM, including daratumumab and isatuximab (SAR650984), respectively. Studies have shown that anti-CD38 therapies are effective in the treatment of relapsed/refractory MM and are well tolerated, with infusion reactions being the most common side effects. They can be used as monotherapy or in combination with immunomodulatory agents, such as pomalidomide, or proteasome inhibitors to potentiate their activity. Here we examine isatuximab and several anti-CD38 agents in development that were generated using new antibody engineering techniques and that may lead to more effective CD38 targeting. We also summarize trials assessing these antibodies in MM, other malignancies, and solid organ transplantation. Finally, we propose that further research on the mechanisms of resistance to anti-CD38 therapy and the development of biomarkers and new backbone regimens with CD38 antibodies will be important steps in building more personalized treatment for patients with MM.

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“…The proportion of patients with cytogenetics reported is often low in clinical trials (e.g., 47% of patients in FIRST; 9 53% in ASPIRE 52 ), leading to a high level of missing information, although this proportion was higher in the TOURMALINE-MM1 (76%) 20 , CASTOR (71%) 16 , and POLLUX (77%) 15 trials. Similarly, these data appear to be limited in analyses of routine practice, with conventional cytogenetic and fluorescence in situ hybridization (FISH) analysis being reported in only 37–63.2% of patients in recent real-world analyses; 24 , 53 , 54 a contributory factor may be the limited availability of these analytical techniques, notably FISH, at different sites around the world. This raises the possibility of ‘hidden’ imbalances in prognostic markers across these studies, making indirect comparisons even more difficult.…”

Section: The Impact Of Disease and Patient Heterogeneity On Clinical mentioning

confidence: 99%

“…Refractoriness to previous therapy 55 and number and type of previous lines of therapy 56 are known determinants of response to subsequent therapy; however, these may be confounded by the use of different definitions for determining ‘refractory’ disease and classifying a line of therapy between clinical trials and compared with the real-world setting. Patients typically have poorer outcomes with successive lines of therapy, including shorter disease-free intervals or periods of disease control, both in clinical trials and in the real-world setting 24 , 38 , 57 , associated with increasing disease refractoriness and accumulating frailty/comorbidities. Standard clinical trial eligibility criteria typically exclude more heavily pretreated patients 38 .…”

Section: The Impact Of Disease and Patient Heterogeneity On Clinical mentioning

confidence: 99%

Interpreting clinical trial data in multiple myeloma: translating findings to the real-world setting

Richardson

Miguel

Moreau³

et al. 2018

Blood Cancer Journal

183

174

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Substantial improvements in survival have been seen in multiple myeloma (MM) over recent years, associated with the introduction and widespread use of multiple novel agents and regimens, as well as the emerging treatment paradigm of continuous or long-term therapy. However, these therapies and approaches may have limitations in the community setting, associated with toxicity burden, patient burden, and other factors including cost. Consequently, despite improvements in efficacy in the rigorously controlled clinical trials setting, the same results are not always achieved in real-world practice. Furthermore, the large number of different treatment options and regimens under investigation in various MM settings precludes the feasibility of obtaining head-to-head clinical trial data, and there is a temptation to use cross-trial comparisons to evaluate data across regimens. However, multiple aspects, including patient-related, disease-related, and treatment-related factors, can influence clinical trial outcomes and lead to differences between studies that may confound direct comparisons between data. In this review, we explore the various factors requiring attention when evaluating clinical trial data across available agents/regimens, as well as other considerations that may impact the translation of these findings into everyday MM management. We also investigate discrepancies between clinical trial efficacy and real-world effectiveness through a literature review of non-clinical trial data in relapsed/refractory MM on novel agent−based regimens and evaluate these data in the context of phase 3 trial results for recently approved and commonly used regimens. We thereby demonstrate the complexity of interpreting data across clinical studies in MM, as well as between clinical studies and routine-care analyses, with the aim to help clinicians consider all the necessary issues when tailoring individual patients’ treatment approaches.

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Real-world treatment patterns and associated progression-free survival in relapsed/refractory multiple myeloma among US community oncology practices

Abstract: Re-treatment with bortezomib was common; novel agents were reserved for later therapy lines. Overall, the observed PFS associated with real-world treatment sequences were shorter than those reported in clinical trials.

Cited by 39 publications

References 15 publications

A phase I/II dose-escalation study investigating all-oral ixazomib-melphalan-prednisone induction followed by single-agent ixazomib maintenance in transplant-ineligible newly diagnosed multiple myeloma

A phase I/II dose-escalation study investigating all-oral ixazomib-melphalan-prednisone induction followed by single-agent ixazomib maintenance in transplant-ineligible newly diagnosed multiple myeloma

Therapeutic Opportunities with Pharmacological Inhibition of CD38 with Isatuximab

Interpreting clinical trial data in multiple myeloma: translating findings to the real-world setting

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