Effect of thalidomide with melphalan and prednisone on health-related quality of life (HRQoL) in elderly patients with newly diagnosed multiple myeloma: a prospective analysis in a randomized trial

Verelst, S.; Termorshuizen, Fabian; Groot, Carin A Uyl-de; Schaafsma, M. R.; Ammerlaan, A. H. M.; Wittebol, Shulamiet; Sinnige, Harm; Zweegman, Sonja; Kooy, Marinus van Marwijk; Griend, René van der; Lokhorst, Henk M.; Sonneveld, Pieter; Wijermans, Pierre W.

doi:10.1007/s00277-011-1224-1

Cited by 36 publications

(20 citation statements)

References 20 publications

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“…23 In a trial testing the addition of thalidomide to melphalan plus prednisone in patients not suitable for ASCT, Verelst et al reported that despite more frequent and severe adverse events, patients receiving thalidomide reported superior emotional function and future perspectives with no differences detected in global scores, thus supporting a decision to adopt adding thalidomide to melphalan-prednisone as standard treatment based on demonstrated improvements in PFS and survival. 24 As with our trial, thalidomide was associated with poorer physical functioning, constipation, and paresthesias and less insomnia.…”

Section: Discussionmentioning

confidence: 99%

A randomized phase 3 trial of thalidomide and prednisone as maintenance therapy after ASCT in patients with MM with a quality-of-life assessment: the National Cancer Institute of Canada Clinicals Trials Group Myeloma 10 Trial

Stewart

Trudel

Bahlis

et al. 2013

Blood

132

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• Thalidomide and prednisone maintenance after transplantation improves progressionfree but not overall survival.We conducted a randomized, controlled trial comparing thalidomide-prednisone as maintenance therapy with observation in 332 patients who had undergone autologous stem cell transplantation with melphalan 200 mg/m 2 . The primary end point was overall survival (OS); secondary end points were myeloma-specific progression-free survival, progression-free survival, incidence of venous thromboembolism, and health-related quality of life (HRQoL). With a median follow-up of 4.1 years, no differences in OS between thalidomide-prednisone and observation were detected (respective 4-year estimates of 68% vs 60%, respectively; hazard ratio ‫؍‬ 0.77; P ‫؍‬ .18); thalidomide-prednisone was associated with superior myeloma-specific progression-free survival and progression-free survival (for both outcomes, the 4-year estimates were 32% vs 14%; hazard ratio ‫؍‬ 0.56; P < .0001) and more frequent venous thromboembolism (7.3% vs none; P ‫؍‬ .0004). Median survival after first disease recurrence was 27.7 months with thalidomide-prednisone and 34.1 months in the observation group. Nine second malignancies were observed with thalidomide-prednisone versus 6 in the observation group. Those allocated to thalidomideprednisone reported worse HRQoL with respect to cognitive function, dyspnea, constipation, thirst, leg swelling, numbness, dry mouth, and balance problems. We conclude that maintenance therapy with thalidomide-prednisone after autologous stem cell transplantation improves the duration of disease control, but is associated with worsening of patient-reported HRQoL and no detectable OS benefit. (Blood. 2013;121(9):1517-1523)

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Section: Discussionmentioning

confidence: 99%

A randomized phase 3 trial of thalidomide and prednisone as maintenance therapy after ASCT in patients with MM with a quality-of-life assessment: the National Cancer Institute of Canada Clinicals Trials Group Myeloma 10 Trial

Stewart

Trudel

Bahlis

et al. 2013

Blood

132

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“…Improvements in HRQoL have previously been reported during treatment with melphalan, prednisone, lenalidomide followed by lenalidomide maintenance (MPR-R) in patients with NDMM, 39,43 and the addition of thalidomide to MP did not negatively affect HRQoL. 44 However, our results contrast with the HRQoL trade-off reported with bortezomib in the VISTA trial, which compared MPV versus MP in NDMM patients and in which MPV had superior PFS and OS efficacy, but where patients' HRQoL was significantly compromised, especially in the first four cycles of treatment. 45,46 In the FIRST trial, although HRQoL was improved and maintained during the progression-free state, it deteriorated when disease progression occurred, regardless of the treatment received.…”

Section: Discussionmentioning

confidence: 99%

Health-related quality-of-life in patients with newly diagnosed multiple myeloma in the FIRST trial: lenalidomide plus low-dose dexamethasone versus melphalan, prednisone, thalidomide

et al. 2015

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The randomized pivotal phase III FIRST trial (Frontline Investigation of lenalidomide/dexamethasone [Rev/Dex] versus Standard Thalidomide; IFM 2007-01/ MM-020; clinicaltrials.gov identifier: 00689936; EudraCT No. 2007-004823-39) compared the efficacy and safety of Rd, administered continuously until progressive disease (PD) or for a fixed 18-month duration (Rd18), with MPT given for 18 months in NDMM patients who were aged 65 years or over, or who were aged under 65 years and ineligible for stem cell transplantation. Continuous Rd showed improved progression-free survival (PFS) and overall survival (OS) benefit at interim analysis compared with MPT. 19 Although extending survival is clearly the ultimate treatment ©2015 Ferrata Storti Foundation. This is an open-access paper. doi:10.3324/haematol.2014 The online version of this article has a Supplementary Appendix. Manuscript received on November 14, 2014. Manuscript accepted on March 6, 2015 We compared the health-related quality-of-life of patients with newly diagnosed multiple myeloma aged over 65 years or transplant-ineligible in the pivotal, phase III FIRST trial. Patients received: i) continuous lenalidomide and low-dose dexamethasone until disease progression; ii) fixed cycles of lenalidomide and low-dose dexamethasone for 18 months; or iii) fixed cycles of melphalan, prednisone, thalidomide for 18 months. Data were collected using the validated questionnaires (QLQ-MY20, QLQ-C30, and EQ-5D). The analysis focused on the EQ-5D utility value and six domains pre-selected for their perceived clinical relevance. Lenalidomide and low-dose dexamethasone, and melphalan, prednisone, thalidomide improved patients' health-related quality-of-life from baseline over the duration of the study across all pre-selected domains of the QLQ-C30 and EQ-5D. In the QLQ-MY20, lenalidomide and low-dose dexamethasone demonstrated a significantly greater reduction in the Disease Symptoms domain compared with melphalan, prednisone, thalidomide at Month 3, and significantly lower scores for QLQ-MY20 Side Effects of Treatment at all post-baseline assessments except Month 18. Linear mixed-model repeatedmeasures analyses confirmed the results observed in the cross-sectional analysis. Continuous lenalidomide and low-dose dexamethasone delays disease progression versus melphalan, prednisone, thalidomide and has been associated with a clinically meaningful improvement in health-related quality-of-life. These results further establish continuous lenalidomide and low-dose dexamethasone as a new standard of care for initial therapy of myeloma by demonstrating superior health-related quality-of-life during treatment, compared with melphalan, prednisone, thalidomide.Health-related quality-of-life in patients with newly diagnosed multiple myeloma in the FIRST trial: lenalidomide plus low-dose dexamethasone versus melphalan, prednisone, thalidomide [20][21][22][23] In this population, treatment objectives should be to improve disease management by delaying disease progression, optimizing re...

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“…The incidence of PNP has been shown to increase with prolonged use of thalidomide, rising to > 50% (grade ≤ 2 in most patients) after 1 year of treatment [39]. A prospective analysis comparing MP versus MPT followed by thalidomide maintenance in the MPT arm showed that the higher frequency of toxicity associated with MPT does not translate into a negative effect on health-related quality of life and that MPT treatment holds a better patient perspective in elderly patients with newly diagnosed MM [40]. Consensus guidelines for the optimal management of AEs in newly diagnosed MM patients who are older than 65 years or transplant ineligible recommend clinical assessment of the patients prior to and at regular intervals during treatment with MPT.…”

Section: Phase III Studiesmentioning

confidence: 99%

Treatment of Multiple Myeloma: Thalidomide-, Bortezomib-, and Lenalidomide-Induced Peripheral Neuropathy

Koeppen¹

2014

Oncol Res Treat

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Over the last 15 years, substantial progress has been made in the treatment of patients with multiple myeloma (MM). New chemotherapeutic options with the immunomodulatory drugs thalidomide and lenalidomide and with the proteasome inhibitor bortezomib have increased the response rates before and after autologous hematopoietic stem cell transplantation (ASCT). Incorporation of the novel agents into the treatment of newly diagnosed MM and at relapse is now standard of care also for patients with MM not eligible for ASCT. However, the use of thalidomide and bortezomib is frequently associated with a dose-limiting peripheral neuropathy. In order to take full advantage of the therapeutic potential, a risk assessment for neurotoxicity is needed on a case-by-case basis. This assessment includes pre-existing neurological symptoms due to the MM, any comorbidities, and past or planned treatment regimens. The aim is to achieve maximum efficacy while minimizing the risk of developing chemotherapy-induced polyneuropathy (CIPN). This requires a neurological evaluation of the patient at regular intervals, the implementation of preventive measures, and the development of validated therapeutic strategies for emerging neurotoxic side effects. This review focuses on the incidence, prevention, and management of peripheral neurotoxicity due to thalidomide, bortezomib, and lenalidomide in the treatment of MM.

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Effect of thalidomide with melphalan and prednisone on health-related quality of life (HRQoL) in elderly patients with newly diagnosed multiple myeloma: a prospective analysis in a randomized trial

Cited by 36 publications

References 20 publications

A randomized phase 3 trial of thalidomide and prednisone as maintenance therapy after ASCT in patients with MM with a quality-of-life assessment: the National Cancer Institute of Canada Clinicals Trials Group Myeloma 10 Trial

A randomized phase 3 trial of thalidomide and prednisone as maintenance therapy after ASCT in patients with MM with a quality-of-life assessment: the National Cancer Institute of Canada Clinicals Trials Group Myeloma 10 Trial

Health-related quality-of-life in patients with newly diagnosed multiple myeloma in the FIRST trial: lenalidomide plus low-dose dexamethasone versus melphalan, prednisone, thalidomide

Treatment of Multiple Myeloma: Thalidomide-, Bortezomib-, and Lenalidomide-Induced Peripheral Neuropathy

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