: We conducted a pooled analysis of two phase III trials, RV-MM-EMN-441 and EMN01, to compare maintenance with lenalidomide-prednisone vs. lenalidomide in newly diagnosed transplant-eligible and -ineligible myeloma patients. Primary endpoints were progression-free survival, progression-free survival 2 and overall survival with both regimens. A secondary aim was to evaluate the impact of duration of maintenance on overall survival and on outcome after relapse. A total of 625 patients (lenalidomide-prednisone arm, n = 315; lenalidomide arm, n = 310) were analyzed. The median follow-up was 58 months. Median progression-free survival (25 vs. 19 months; p = 0.08), progression-free survival 2 (56 vs. 49 months; p = 0.9) and overall survival (73 months vs. NR; p = 0.08) were not significantly different between the two arms. Toxicity profiles of lenalidomide-prednisone and lenalidomide were similar, with the exception of neutropenia that was higher in the lenalidomide arm (grade ≥ 3: 9% vs. 19%, p < 0.001), without an increase in the rate of infections. Overall survival (median NR vs. 49 months, p < 0.001), progression-free survival from relapse (median 35 vs. 24 months, p = 0.004) and overall survival from relapse (median not reached vs. 41 months, p = 0.002) were significantly longer in patients continuing maintenance for ≥2 years. We showed that the addition of prednisone at 25 or 50 mg every other day (eod) to lenalidomide maintenance did not induce any significant advantage.

• Klíčová slova
• lenalidomide, maintenance, multiple myeloma, newly diagnosed, prednisone,
• Publikační typ
• časopisecké články MeSH

IMPORTANCE: Several trials demonstrated the impact of novel agent-based maintenance in newly diagnosed multiple myeloma (NDMM), but there is no current evidence demonstrating the superiority of one regimen over the other, owing to the lack of direct/indirect comparisons. OBJECTIVE: To analyze and compare the effectiveness of different maintenance regimens in NDMM via a network meta-analysis. DATA SOURCES: We performed 2 independent searches in PubMed and Cochrane databases, and then we identified all the records registered after 1999 and on or before November 20, 2017. STUDY SELECTION: By blinded review, we identified prospective phase 3 randomized trials evaluating novel agent-based maintenance in patients with NDMM; the included studies compared at least 2 maintenance approaches; comparators included placebo and no maintenance. From 364 screened records, 11 studies were included. DATA EXTRACTION AND SYNTHESIS: We followed (independent extraction) the guidelines provided by the PRISMA Report and the EQUATOR Network. The evidence was synthesized using a network meta-analysis (NMA). To allow comparison of all treatments, no maintenance was selected as common comparator and the effect of placebo was assumed to be the same as no treatment. The best option was identified by a Bayesian consistency model based on hazard ratio (HR), 95% credible interval (CrI), probability of being the best treatment (PbBT), and median ranking distribution (MedR). MAIN OUTCOMES AND MEASURES: Outcomes of interest were progression-free survival (PFS) and overall survival (OS). RESULTS: Eleven trials and 8 treatments including a total of 5073 participants were included. By PFS analysis, lenalidomide-based regimens (lenalidomide-prednisone, lenalidomide alone) were identified as the most effective options (HR, 0.39 [95% CrI, 0.28-0.53] and 0.47 [95% CrI, 0.39-0.55], respectively; MedR, 1 and 2; overall PbBT, 74%). Four treatments (thalidomide-interferon, thalidomide-bortezomib, bortezomib-prednisone, thalidomide alone) showed an HR in favor of maintenance. By OS analysis, lenalidomide alone was identified as the best option (HR, 0.76; 95% CrI, 0.51-1.16; MedR, 2; PbBT, 38%), followed by bortezomib-thalidomide and bortezomib-prednisone. Similar features were noticed in the restricted network including transplant trials, in the sensitivity analysis, and in most of the prognostic subgroups. CONCLUSIONS AND RELEVANCE: Based on PFS and OS results of this NMA, lenalidomide maintenance appears to be the best treatment option, by synthesizing the available evidence of novel agent-based maintenance in the past 20 years.

• MeSH
• klinické zkoušky, fáze III jako téma MeSH
• lenalidomid aplikace a dávkování   MeSH
• mnohočetný myelom diagnóza   farmakoterapie   MeSH
• přežití bez známek nemoci MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• randomizované kontrolované studie jako téma MeSH
• síťová metaanalýza MeSH
• udržovací chemoterapie metody   MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• systematický přehled MeSH
• Názvy látek
• lenalidomid MeSH

Multiple myeloma (MM) is a clonal B-cell malignancy characterized by aberrant expansion of plasma cells within bone marrow and extramedullary sites. It is one of the most common haematological malignancies; it accounts for 1.4% of all tumours and is responsible for 2% of cancer-related mortality. Over the last decades, the paradigm of MM therapy has changed dramatically - from the conventional combination of oral melphatan + prednisone, high-dose chemotherapy with stem cell (ASCT) support for younger patients to the present paradigm with the use of one (or more) of 3 major new targeted agents - the first-in class proteasome inhibitor bortezomib, the immunomodulatory drug thalidomide, and its more potent derivative lenalidomide. Their use as a part of initial therapy is associated with high overall response rates as well as high rates of complete response (CR), both for elderly patients unable to undergo ASCT and for younger patients treated prior to ASCT. Altogether, the advent of novel agents has resulted in a 50% improvement in median survival. Moreover, the development of new drug classes based on preclinical rationale and the introduction of next-generation agents are likely to further expand treatment options and improve outcomes for especially relapsed MM. This review highlights important historic landmarks as well as more recent events that have played an important role in the evolution of myeloma targeted therapy.

• Klíčová slova
• ASCT, Bortezomib, Lenalidomide, Multiple myeloma,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Recent developments have led to remarkable improvements in the assessment and treatment of patients with multiple myeloma (MM). New technologies have become available to precisely evaluate the biology and extent of the disease, including information about cytogenetics and genetic abnormalities, extramedullary manifestations and minimal residual disease. New, more effective drugs have been introduced into clinical practice, which enable clinicians to significantly improve the outcome of patients but also pose new challenges for the prevention and management of their specific side effects. Given these various new options and challenges, it is important to identify the minimal requirements for diagnosis and treatment of patients, as access to the most sophisticated advances may vary depending on local circumstances. Here, we propose the minimal requirements and possible options for diagnosis, monitoring and treatment of patients with multiple myeloma.

• MeSH
• lidé MeSH
• mnohočetný myelom patofyziologie   terapie   MeSH
• monitorování fyziologických funkcí MeSH
• recidiva MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH