Melphalan, prednisone, and thalidomide vs melphalan, prednisone, and lenalidomide (ECOG E1A06) in untreated multiple myeloma

Stewart, A. Keith; Jacobus, Susanna; Fonseca, Rafaël; Weiss, Matthias; Callander, Natalie S.; Chanan‐Khan, Asher; Rajkumar, S. Vincent

doi:10.1182/blood-2014-12-613927

Cited by 83 publications

(65 citation statements)

References 31 publications

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“…This translated into a better quality of life. 15 In contrast to the ECOG trial, in which less than grade 4 hematologic toxicity was not required to be reported, in our study, hematologic toxicity could be determined. Grade 3/4 hematologic toxicity was significantly higher in the MPR-R arm, requiring growth factor support in 38% of patients.…”

Section: Discussionmentioning

confidence: 75%

“…Importantly, a recent Eastern Cooperative Oncology Group (ECOG) study, comparing similar regimens, also found equal efficacy of MPR-R and MPT-T, with a PFS in the MPR-R arm even being slightly worse compared with what we observed, which might be explained by a lower dose of melphalan in the MPR arm: 5 vs 9 mg/m 2 in the MPT-T arm. 15 Therefore, the only explanation for the superior PFS in the MM015 trial is the difference in follow-up: 30 vs 36 months in our trial, with a considerable number of patients not having reached the median PFS yet. This is supported by the fact that at 12 and 20 months, the percentage of patients without progression is rather (24) 46 (14) II 57 (18) 10 (3) III 21 (7) 2 ( (9) 23 (12) II 50 (31) 10 (5) III 29 (18) 3 (2) IV -- Number of patients discontinuing maintenance (%)…”

Section: Discussionmentioning

confidence: 99%

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Melphalan, prednisone, and lenalidomide versus melphalan, prednisone, and thalidomide in untreated multiple myeloma

Zweegman¹,

Holt²,

Mellqvist

et al. 2016

Blood

103

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Key Points• In a multicenter, randomized phase 3 trial, MPR-R was not superior over MPT-T with respect to response rate, PFS, and OS.• Grade 3/4 hematologic toxicity requiring growth factor support occurred with MPR-R vs clinically significant neuropathy with MPT-T.The combination of melphalan, prednisone, and thalidomide (MPT) is considered standard therapy for newly diagnosed patients with multiple myeloma who are ineligible for stem cell transplantation. Long-term treatment with thalidomide is hampered by neurotoxicity. Melphalan, prednisone, and lenalidomide, followed by lenalidomide maintenance therapy, showed promising results without severe neuropathy emerging. We randomly assigned 668 patients between nine 4-week cycles of MPT followed by thalidomide maintenance until disease progression or unacceptable toxicity (MPT-T) and the same MP regimen with thalidomide being replaced by lenalidomide (MPR-R). This multicenter, open-label, randomized phase 3 trial was undertaken by Dutch-Belgium Cooperative Trial Group for Hematology Oncology and the Nordic Myeloma Study Group (the HOVON87/ NMSG18 trial). The primary end point was progression-free survival (PFS). A total of 318 patients were randomly assigned to receive MPT-T, and 319 received MPR-R. After a median follow-up of 36 months, PFS with MPT-T was 20 months (95% confidence interval [CI], 18-23 months) vs 23 months (95% CI, 19-27 months) with MPR-R (hazard ratio, 0.87; 95% CI, 0.72-1.04; P 5 .12). Response rates were similar, with at least a very good partial response of 47% and 45%, respectively. Hematologic toxicity was more pronounced with MPR-R, especially grades 3 and 4 neutropenia: 64% vs 27%. Neuropathy of at least grade 3 was significantly higher in the MPT-T arm: 16% vs 2% in MPR-R, resulting in a significant shorter duration of maintenance therapy (5 vs 17 months in MPR-R), irrespective of age. MPR-R has no advantage over MPT-T concerning efficacy. The toxicity profile differed with clinically significant neuropathy during thalidomide maintenance vs myelosuppression with

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Section: Discussionmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Melphalan, prednisone, and lenalidomide versus melphalan, prednisone, and thalidomide in untreated multiple myeloma

Zweegman¹,

Holt²,

Mellqvist

et al. 2016

Blood

103

View full text Add to dashboard Cite

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“…Of the 208 full text articles screened and selected for further review, 192 were excluded for the following reasons: 65 did not include a population of interest; 14 did not evaluate an intervention or comparator of interest; 24 did not report on outcomes of interest; 54 had an inappropriate study design; and 35 due to other reasons. The resulting number of RCTs included was 16 (15 presented in full publications, [5,[16][17][18][21][22][23][24][25][26][27][28][29][30][31][32][33] and one presented in a conference abstract [34]). Two additional publications were identified for inclusion through manual searches of conference abstracts, [21,29] for a total of 18 publications reporting on 17 trials.…”

Section: Study Selectionmentioning

confidence: 99%

“…Two additional publications were identified for inclusion through manual searches of conference abstracts, [21,29] for a total of 18 publications reporting on 17 trials. [5,[16][17][18][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] A further two publications were identified providing safety data not available in the principal publications. [35,36] Of note, Fayers et al was excluded due to study design (meta-analysis); however, this study provided HR data for Beksac et al and Waage et al that was not otherwise available.…”

Section: Study Selectionmentioning

confidence: 99%

A systematic literature review and network meta-analysis of treatments for patients with untreated multiple myeloma not eligible for stem cell transplantation

Weisel

Doyen

Dimopoulos

et al. 2016

Leukemia & Lymphoma

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A systematic literature review and network meta-analysis of treatments for patients with untreated multiple myeloma not eligible for stem cell transplantation, Leukemia & Lymphoma, 58:1, 153-161, DOI: 10.1080/10428194.2016 In newly diagnosed multiple myeloma (MM), patients ineligible for front-line autologous stem cell transplantation (ASCT), melphalan and prednisone (MP) with thalidomide (MPT) or bortezomib (VMP) are standard first-line therapeutic options. Despite new treatment regimens incorporating bortezomib or lenalidomide, MM remains incurable. The FIRST study demonstrated significant improvement in progression-free survival (PFS) and overall survival (OS) for the combination of lenalidomide and low-dose dexamethasone (Rd) until progression vs. MPT in transplant-ineligible ndMM patients. However, to date no head-to-head randomized controlled trials (RCTs) have compared Rd or MPT versus VMP. We conducted a network meta-analysis using RCTs identified through a systematic literature review to evaluate the relative efficacy of Rd versus other regimens on survival endpoints in previously untreated MM patients ineligible for ASCT. In this analysis, Rd was associated with a significant PFS and survival advantage versus other first-line treatments (VMP, MPT, MP), challenging the role of alkylators in this setting. ARTICLE HISTORY

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“…[4][5][6][7][8]22 These prospective, retrospective and meta analysis data determined SPM frequencies at 4%-6% (Table 2). …”

Section: Occurrence and Distribution Of Different Additional Malignanmentioning

confidence: 99%

Large registry analysis to accurately define second malignancy rates and risks in a well-characterized cohort of 744 consecutive multiple myeloma patients followed-up for 25 years

et al. 2015

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Melphalan, prednisone, and thalidomide vs melphalan, prednisone, and lenalidomide (ECOG E1A06) in untreated multiple myeloma

Abstract: Key Points In a randomized phase 3 trial, overall response rates, PFS, and overall survival were similar between MPT-T and mPR-R. Toxicity with both regimens was common, but mPR-R was better tolerated, and patients on the mPR-R regimen reported better quality of life.

Cited by 83 publications

References 31 publications

Melphalan, prednisone, and lenalidomide versus melphalan, prednisone, and thalidomide in untreated multiple myeloma

Melphalan, prednisone, and lenalidomide versus melphalan, prednisone, and thalidomide in untreated multiple myeloma

A systematic literature review and network meta-analysis of treatments for patients with untreated multiple myeloma not eligible for stem cell transplantation

Large registry analysis to accurately define second malignancy rates and risks in a well-characterized cohort of 744 consecutive multiple myeloma patients followed-up for 25 years

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