• MeSH
• dexamethason terapeutické užití   MeSH
• humanizované monoklonální protilátky terapeutické užití   MeSH
• lidé MeSH
• lokální recidiva nádoru farmakoterapie   MeSH
• mnohočetný myelom * farmakoterapie   MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• dopisy MeSH
• práce podpořená grantem MeSH
• Názvy látek
• carfilzomib MeSH Prohlížeč
• dexamethason MeSH
• humanizované monoklonální protilátky MeSH
• isatuximab MeSH Prohlížeč

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

Autologous stem cell transplantation (ASCT) is a standard treatment for eligible multiple myeloma (MM) patients, but many patients will relapse after ASCT and require subsequent therapy. The proteasome inhibitor carfilzomib is approved for relapsed or refractory MM (RRMM). In phase 3 trials, carfilzomib-based regimens (ASPIRE, carfilzomib-lenalidomide-dexamethasone; ENDEAVOR, carfilzomib-dexamethasone) demonstrated superior progression-free survival (PFS) compared with standard therapies for RRMM (ASPIRE: lenalidomide-dexamethasone; ENDEAVOR, bortezomib-dexamethasone). This subgroup analysis of ASPIRE and ENDEAVOR evaluated outcomes according to prior ASCT status. In total, 446 patients in ASPIRE and 538 in ENDEAVOR had prior ASCT. Median PFS was longer for carfilzomib-based regimens vs non-carfilzomib-based regimens for patients with prior ASCT (ASPIRE: 26.3 vs 17.8 months (hazard ratio (HR)=0.68); ENDEAVOR: not estimable vs 10.2 months (HR=0.61)), those with one prior line of therapy that included ASCT (ASPIRE: 29.7 vs 17.8 months (HR=0.70); ENDEAVOR: not estimable vs 11.2 months (HR=0.46)), and those without prior ASCT (ASPIRE: 26.4 vs 16.6 months (HR=0.76); ENDEAVOR: 17.7 vs 8.5 months (HR=0.43)). Overall response rates also favored the carfilzomib-based regimens. No new safety signals were detected. This analysis suggests that carfilzomib-based treatment may lead to improvement in PFS and response rates regardless of prior transplant status. Further evaluation is warranted.

• MeSH
• autologní transplantace MeSH
• dospělí MeSH
• Kaplanův-Meierův odhad MeSH
• lidé středního věku MeSH
• lidé MeSH
• mnohočetný myelom farmakoterapie   mortalita   patologie   terapie   MeSH
• oligopeptidy aplikace a dávkování   MeSH
• opakovaná terapie MeSH
• pooperační péče MeSH
• protokoly protinádorové kombinované chemoterapie škodlivé účinky   terapeutické užití   MeSH
• recidiva MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• transplantace hematopoetických kmenových buněk MeSH
• výsledek terapie 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
• práce podpořená grantem MeSH
• Názvy látek
• carfilzomib MeSH Prohlížeč
• oligopeptidy MeSH

Prior treatment exposure in patients with relapsed/refractory multiple myeloma may affect outcomes with subsequent therapies. We analyzed efficacy and safety according to prior treatment in the phase 3 TOURMALINE-MM1 study of ixazomib-lenalidomide-dexamethasone (ixazomib-Rd) versus placebo-Rd. Patients with relapsed/refractory multiple myeloma received ixazomib-Rd or placebo-Rd. Efficacy and safety were evaluated in subgroups defined according to type (proteasome inhibitor [PI] and immunomodulatory drug) and number (1 vs. 2 or 3) of prior therapies received. Of 722 patients, 503 (70%) had received a prior PI, and 397 (55%) prior lenalidomide/thalidomide; 425 patients had received 1 prior therapy, and 297 received 2 or 3 prior therapies. At a median follow up of ~15 months, PFS was prolonged with ixazomib-Rd vs. placebo-Rd regardless of type of prior therapy received; HR 0.739 and 0.749 in PI-exposed and -naïve patients, HR 0.744 and 0.700 in immunomodulatory-drug-exposed and -naïve patients, respectively. PFS benefit with ixazomib-Rd vs. placebo-Rd appeared greater in patients with 2 or 3 prior therapies (HR 0.58) and in those with 1 prior therapy without prior transplant (HR 0.60) versus those with 1 prior therapy and transplant (HR 1.23). Across all subgroups, toxicity was consistent with that seen in the intent-to-treat population. In patients with relapsed/refractory multiple myeloma, ixazomib-Rd was associated with a consistent clinical benefit vs. placebo-Rd regardless of prior treatment with bortezomib or immunomodulatory drugs. Patients with 2 or 3 prior therapies, or 1 prior therapy without transplant seemed to have greater benefit than patients with 1 prior therapy and transplant. TOURMALINE-MM1 registered at clinicaltrials.gov identifier: 01564537.

• MeSH
• chemorezistence MeSH
• dexamethason aplikace a dávkování   MeSH
• glycin aplikace a dávkování   analogy a deriváty   MeSH
• Kaplanův-Meierův odhad MeSH
• lenalidomid MeSH
• lidé MeSH
• mnohočetný myelom farmakoterapie   mortalita   patologie   MeSH
• následné studie MeSH
• opakovaná terapie MeSH
• protokoly protinádorové kombinované chemoterapie škodlivé účinky   terapeutické užití   MeSH
• recidiva MeSH
• sloučeniny boru aplikace a dávkování   MeSH
• thalidomid aplikace a dávkování   analogy a deriváty   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• dexamethason MeSH
• glycin MeSH
• ixazomib MeSH Prohlížeč
• lenalidomid MeSH
• sloučeniny boru MeSH
• thalidomid MeSH