BACKGROUND: Multiple myeloma (MM) patients with high cytogenetic risk have poor outcomes. In CASTOR, daratumumab plus bortezomib/dexamethasone (D-Vd) prolonged progression-free survival (PFS) versus bortezomib/dexamethasone (Vd) alone and exhibited tolerability in patients with relapsed or refractory MM (RRMM). METHODS: This subgroup analysis evaluated D-Vd versus Vd in CASTOR based on cytogenetic risk, determined using fluorescence in situ hybridization and/or karyotype testing performed locally. High-risk patients had t(4;14), t(14;16), and/or del17p abnormalities. Minimal residual disease (MRD; 10-5 sensitivity threshold) was assessed via the clonoSEQ® assay V2.0. Of the 498 patients randomized, 40 (16%) in the D-Vd group and 35 (14%) in the Vd group were categorized as high risk. RESULTS: After a median follow-up of 40.0 months, D-Vd prolonged median PFS versus Vd in patients with standard (16.6 vs 6.6 months; HR, 0.26; 95% CI, 0.19-0.37; P < 0.0001) and high (12.6 vs 6.2 months; HR, 0.41; 95% CI, 0.21-0.83; P = 0.0106) cytogenetic risk. D-Vd achieved deep responses, including higher rates of MRD negativity and sustained MRD negativity versus Vd, regardless of cytogenetic risk. The safety profile was consistent with the overall population of CASTOR. CONCLUSION: These updated data reinforce the effectiveness and tolerability of daratumumab-based regimens for RRMM, regardless of cytogenetic risk status. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02136134 . Registered 12 May 2014.

• Klíčová slova
• Clinical trials, Multiple myeloma, Myeloma therapy,
• MeSH
• abnormální karyotyp MeSH
• bortezomib aplikace a dávkování   MeSH
• dexamethason aplikace a dávkování   MeSH
• doba přežití bez progrese choroby MeSH
• dospělí MeSH
• hybridizace in situ fluorescenční MeSH
• Kaplanův-Meierův odhad MeSH
• lidé středního věku MeSH
• lidé MeSH
• mnohočetný myelom farmakoterapie   genetika   patologie   MeSH
• monoklonální protilátky aplikace a dávkování   MeSH
• následné studie MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• recidiva MeSH
• reziduální nádor MeSH
• riziko MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH
• Názvy látek
• bortezomib MeSH
• daratumumab MeSH Prohlížeč
• dexamethason MeSH
• monoklonální protilátky MeSH

The phase 3 A.R.R.O.W. study demonstrated that treatment with once-weekly carfilzomib (70 mg/m2) and dexamethasone (once-weekly Kd70 mg/m2) improved progression-free survival compared with twice-weekly carfilzomib (27 mg/m2) and dexamethasone (twice-weekly Kd27 mg/m2) in patients with relapsed and refractory multiple myeloma (RRMM; median, 11.2 versus 7.6 months; hazard ratio [HR] = 0.69; 95% confidence interval, 0.54-0.88; P = 0.0029). Once-weekly dosing also improved response rates and depth of response. We performed a subgroup analysis from A.R.R.O.W. according to age (<65, 65-74, or ≥75 years), renal function (creatinine clearance <50, ≥50-<80, or ≥80 mL/min), number of prior therapies (2 or 3), and bortezomib-refractory status (yes or no). Compared with twice-weekly Kd27 mg/m2, once-weekly Kd70 mg/m2 reduced the risk of progression or death (HR = 0.60-0.85) and increased overall response rates in nearly all the examined subgroups, consistent with reports in the overall A.R.R.O.W. population. The safety profiles of once-weekly Kd70 mg/m2 across subgroups were also generally consistent with those in the overall population. Findings from this subgroup analysis generally demonstrate a favorable benefit-risk profile of once-weekly Kd70 mg/m2, further supporting once-weekly carfilzomib dosing as an appropriate treatment option for patients with RRMM, regardless of baseline patient and disease characteristics.

• MeSH
• doba přežití bez progrese choroby MeSH
• lidé MeSH
• mnohočetný myelom farmakoterapie   mortalita   MeSH
• oligopeptidy farmakologie   terapeutické užití   MeSH
• progrese nemoci MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• carfilzomib MeSH Prohlížeč
• oligopeptidy MeSH

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.

• MeSH
• disparity zdravotní péče MeSH
• interpretace statistických dat * MeSH
• klinické zkoušky jako téma * MeSH
• komorbidita MeSH
• lidé MeSH
• mnohočetný myelom diagnóza   epidemiologie   mortalita   terapie   MeSH
• prognóza MeSH
• staging nádorů MeSH
• výsledek terapie MeSH
• výzkumný projekt MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND: In ASPIRE, carfilzomib, lenalidomide, and dexamethasone (KRd) significantly improved progression-free survival (PFS) and response rates versus lenalidomide and dexamethasone (Rd) in patients with relapsed multiple myeloma. Per protocol, patients received KRd for a maximum of 18 cycles followed by Rd to progression, so the benefit/risk profile of KRd to progression was not established. METHODS: This post hoc analysis evaluated the efficacy and safety of KRd versus Rd at 18 months from randomization. Cumulative rates of complete response (CR) or better over time and PFS hazard ratio (HR) at 18 months were evaluated for KRd versus Rd. PFS HRs were also assessed according to cytogenetic risk, prior lines of therapy, and prior bortezomib treatment. Cox regression analysis was used to evaluate PFS HRs. RESULTS: The hazard ratio (HR) for PFS at 18 months was 0.58 versus 0.69 for the overall ASPIRE study. Patients with high-risk cytogenetics, ≥ 1 prior lines of therapy, and prior bortezomib exposure benefited from KRd up to 18 months versus Rd. The HRs for PFS at 18 months in the pre-defined subgroups were lower than those in the overall study. The difference in the proportion of KRd and Rd patients achieving at least a complete response (CR) increased dramatically over the first 18 months and then remained relatively constant. The safety profile at 18 months was consistent with previous findings. CONCLUSIONS: The improved PFS HR at 18 months and the continued increase in CR rates for KRd through 18 cycles suggest that there may be a benefit of continued carfilzomib treatment. TRIAL REGISTRATION: Clinical trials.gov NCT01080391 . Registered 2 March 2010.

• Klíčová slova
• Clinical research, Clinical trials, Multiple myeloma, Myeloma therapy,
• MeSH
• dexamethason farmakologie   terapeutické užití   MeSH
• doba přežití bez progrese choroby MeSH
• lenalidomid farmakologie   terapeutické užití   MeSH
• lidé MeSH
• mnohočetný myelom farmakoterapie   mortalita   patologie   MeSH
• oligopeptidy farmakologie   terapeutické užití   MeSH
• protokoly protinádorové kombinované chemoterapie farmakologie   terapeutické užití   MeSH
• recidiva MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• práce podpořená grantem MeSH
• Názvy látek
• carfilzomib MeSH Prohlížeč
• dexamethason MeSH
• lenalidomid MeSH
• oligopeptidy MeSH