• MeSH
• COVID-19 * komplikace   MeSH
• embolie a trombóza * etiologie   MeSH
• hematologické testy MeSH
• klinická studie jako téma MeSH
• krvácení etiologie   MeSH
• lidé MeSH
• precipitační faktory MeSH
• rizikové faktory kardiovaskulárních chorob MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

• Publikační typ
• souhrny MeSH

• MeSH
• COVID-19 MeSH

BACKGROUND: Dose modifications in response to adverse events (AEs) can maintain tumor response and improve therapy tolerability. We conducted a post-hoc analysis of the efficacy and safety of reduced selinexor doses in the BOSTON trial (NCT03110562). PATIENTS AND METHODS: Efficacy, safety, and quality of life (QoL) in 195 patients with relapsed/refractory multiple myeloma randomized to once-weekly (QW) selinexor (100 mg), QW subcutaneous bortezomib (1.3 mg/m2), and twice-weekly dexamethasone (20 mg) were compared between patients with dose reductions and those without. RESULTS: In total, 126 patients (65%) had selinexor dose reductions (median dose 71.4 mg/wk). In patients with dose reductions versus those without median progression-free survival was 16.6 months (95% CI 12.9-not evaluable [NE]) versus 9.2 months [95% CI 6.8-15.5]), overall response rate was 81.7% (95% CI 73.9-88.1%) versus 66.7% (95% CI 54.3-77.6%), ≥very good partial response was (51.6% [95% CI 42.5-60.6%] vs. 31.9% [95% CI 21.2-44.2]), median duration of response was not reached (95% CI 13.8-NE) versus 12.0 months (95% CI 8.3-NE), and time to next treatment was 22.6 months (95% CI 14.6-NE) versus 10.5 months (95% CI 6.3-18.2). Mean best change from baseline on the EORTC QLQ-C30 Global Health Status/QoL scale was 10.0 ± 20.5 versus 4.0 ± 20.9. Duration-adjusted AE rates that were lower after selinexor dose reduction included thrombocytopenia (62.5% before vs. 47.6% after), nausea (31.6% vs. 7.3%), fatigue (28.1% vs. 9.9%), decreased appetite (21.5% vs. 6.4%), anemia (17.9% vs. 10.3%), and diarrhea (12.9% vs. 5.2%). CONCLUSION: Appropriate dose reductions in response to AEs of the 100 mg selinexor starting dose in the BOSTON study were associated with improved efficacy, reduced AE rates and improved QoL.

• MeSH
• dexamethason terapeutické užití   MeSH
• kvalita života * MeSH
• lidé MeSH
• mnohočetný myelom * farmakoterapie   MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• vysazování léků MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH

Twice-weekly carfilzomib (27 mg/m2) plus lenalidomide and dexamethasone (KRd27) is a standard of care in relapsed/refractory multiple myeloma (RRMM). Once-weekly carfilzomib regimens have shown clinical benefits with improved patient convenience. This open-label, phase 3, multicenter, randomized study aimed to demonstrate noninferiority of the overall response rate (ORR) for once-weekly carfilzomib (56 mg/m2) plus Rd (KRd56) vs twice-weekly KRd27 in RRMM. A total of 454 patients were randomized (1:1) to receive carfilzomib as once-weekly 30-minute infusions of 56 mg/m2 (KRd56; n = 228) or twice-weekly 10-minute infusions of 27 mg/m2 (KRd27; n = 226). Baseline characteristics were balanced between groups. ORR was 82.5% (95% confidence interval [CI], 76.9-87.2) in the once-weekly group vs 86.3% (95% CI, 81.1-90.5) in the twice-weekly group (risk ratio, 0.954 [95% CI, 0.882-1.032]) and did not meet the threshold for statistical significance of noninferiority (P = .0666). Complete response (CR) or better was obtained in 46.9% of patients in the once-weekly arm and 36.3% in the twice-weekly arm. The proportions of patients who achieved CR and were also assessed negative for minimal residual disease were 21.5% and 18.1%, respectively (odds ratio, 1.235 [95% CI, 0.775-1.970]). Progression-free survival was comparable between groups (hazard ratio, 0.945 [95% CI, 0.617-1.447]). The safety profile was similar for both groups. In conclusion, although statistical significance for noninferiority of ORR was not achieved, the efficacy and safety of once-weekly KRd56 were similar to those of twice-weekly KRd27, and once-weekly KRd56 may be an effective and convenient treatment option for patients with RRMM. This trial was registered at www.ClinicalTrials.gov as #NCT03859427.

• MeSH
• dexamethason * aplikace a dávkování   terapeutické užití   MeSH
• dospělí MeSH
• lenalidomid * aplikace a dávkování   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mnohočetný myelom * farmakoterapie   mortalita   MeSH
• oligopeptidy * aplikace a dávkování   terapeutické užití   MeSH
• protokoly protinádorové kombinované chemoterapie * terapeutické užití   škodlivé účinky   MeSH
• recidiva MeSH
• rozvrh dávkování léků MeSH
• senioři nad 80 let MeSH
• senioři 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
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie 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.

• 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

INTRODUCTION: Melphalan flufenamide (melflufen), a first-in-class alkylating peptide-drug conjugate, plus dexamethasone demonstrated superior progression-free survival (PFS) but directionally different overall survival (OS) favoring pomalidomide (hazard ratio [HR], 1.10) in OCEAN. METHODS: These analyses further investigated prognostic subgroups impacting survival in updated data from the randomized, phase 3 OCEAN study (NCT03151811; date: February 3, 2022) and the phase 2 HORIZON study (NCT02963493; date: February 2, 2022). RESULTS: In OCEAN, subgroups prognostic for OS were age (P = .011; <65 years favored pomalidomide) and no previous autologous stem cell transplant (ASCT) or progression >36 months after ASCT (P = .001; favored melflufen). Overall, 245 of 495 (49%) patients randomized had received a previous ASCT, of which 202 (82%) had progressed within 36 months following their ASCT. When excluding patients who had progressed <36 months post-ASCT (melflufen group, n = 145; pomalidomide group, n = 148), median OS was 23.6 months with melflufen and 19.8 months with pomalidomide (HR, 0.83 [95% CI, 0.62-1.12]; P = .22). Among patients with triple-class refractory disease in HORIZON, patients who had progressed <36 months post-ASCT (n = 58) had a lower response rate and shorter duration of response and PFS than the remaining patients (n = 52). Safety was consistent with previous reports. CONCLUSION: These analyses demonstrate a consistent benefit for melflufen and dexamethasone in patients with relapsed/refractory multiple myeloma who have not received an ASCT or progressed >36 months after receiving an ASCT (ClinicalTrials.gov identifier: NCT03151811).

• MeSH
• autologní transplantace MeSH
• dexamethason terapeutické užití   MeSH
• hodnocení rizik MeSH
• klinické zkoušky, fáze II jako téma MeSH
• klinické zkoušky, fáze III jako téma MeSH
• lidé MeSH
• melfalan terapeutické užití   MeSH
• mnohočetný myelom * farmakoterapie   MeSH
• následné studie MeSH
• protokoly protinádorové kombinované chemoterapie škodlivé účinky   MeSH
• randomizované kontrolované studie jako téma MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

We examined effects of carfilzomib-dexamethasone (Kd56) versus bortezomib-dexamethasone (Vd) on health-related quality of life (HR-QoL) in relapsed/refractory multiple myeloma (MM) patients from the ENDEAVOR study. HR-QoL was assessed by the European Organisation for Research and Treatment of Cancer QoL Questionnaire (QLQ-C30), MM-specific module (QLQ-MY20), and Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT-GOG-Ntx) "Additional Concerns" neurotoxicity subscale. The QLQ-C30 Global Health Status (GHS)/QoL scale and seven prespecified subscales were compared between groups using mixed model for repeated measures. Of 929 randomized patients, 911 with ≥1 post-baseline assessment were included. Kd56 was associated with statistically significant improvements in GHS/QoL, fatigue, pain, side effects, and FACT/GOG-Ntx scores versus Vd, although mean differences did not meet thresholds for clinical significance. The Kd56 group had longer time to deterioration (TTD) in GHS/QoL (median 3.7 versus 2.8 months, p = 0.0046), physical function (5.6 versus 3.7 months, p = 0.0390), nausea/vomiting (17.6 versus 8.2 months, p = 0.0358), side effects (6.4 versus 3.7 months p < 0.0001), and FACT/GOG-Ntx (11.1 versus 5.5 months, p = 0.0004). Overall, Kd56 resulted in statistically but not clinically significant improvements in mean GHS/QoL scores versus Vd. Treatment with Kd56 versus Vd also significantly prolonged TTD in GHS/QoL, physical function, nausea/vomiting, side effects, and FACT/GOG-Ntx.

• MeSH
• adherence pacienta MeSH
• bortezomib MeSH
• chemorezistence MeSH
• dexamethason MeSH
• kvalita života * MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru MeSH
• mnohočetný myelom diagnóza   farmakoterapie   epidemiologie   MeSH
• oligopeptidy MeSH
• protokoly protinádorové kombinované chemoterapie škodlivé účinky   terapeutické užití   MeSH
• průzkumy a dotazníky MeSH
• průzkumy zdravotní péče MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• staging nádorů MeSH
• výsledek terapie MeSH
• Check Tag
• 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
• randomizované kontrolované studie 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

OBJECTIVES: Health-related quality of life (HRQoL) is particularly important during maintenance therapy (MT) in newly diagnosed multiple myeloma post-transplant, when disease symptoms are limited. METHODS: We assessed HRQoL in patients randomised to 26 cycles of MT (ixazomib vs placebo) in TOURMALINE-MM3 (NCT02181413). RESULTS: The characteristics at study entry were well-balanced between ixazomib (n = 386) and placebo (n = 251) arms. At study entry, EORTC QLQ-C30 and MY20 scores were high for functional scales and low for symptom scales and were comparable with those of the general population. Changes in subscale scores across intervals, analysed over 30 four-week intervals using a linear mixed-effects model, were generally small and similar between arms for the EORTC QLQ-C30 Global Health Status/QoL, Physical Functioning, and Pain subscales and EORTC QLQ-MY20 Disease Symptoms subscale and Peripheral Neuropathy item. EORTC QLQ-C30 Nausea/Vomiting and Diarrhoea subscales were consistently worse for ixazomib than for placebo, in line with the ixazomib toxicity profile. Even when least-squares mean differences between arms were statistically significant, none reached the established minimal important clinical difference of 10 in multiple myeloma. CONCLUSIONS: In addition to improvement in progression-free survival with ixazomib, HRQoL was maintained in both arms. Active treatment with ixazomib did not have an adverse impact on HRQoL.

• MeSH
• adherence k farmakoterapii MeSH
• dospělí MeSH
• glycin aplikace a dávkování   škodlivé účinky   analogy a deriváty   terapeutické užití   MeSH
• hodnocení výsledků péče pacientem MeSH
• kombinovaná terapie MeSH
• kvalita života * MeSH
• lidé středního věku MeSH
• lidé MeSH
• mnohočetný myelom diagnóza   epidemiologie   mortalita   terapie   MeSH
• protinádorové látky aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• protokoly protinádorové kombinované chemoterapie škodlivé účinky   terapeutické užití   MeSH
• senioři MeSH
• sloučeniny boru aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• transplantace hematopoetických kmenových buněk MeSH
• udržovací chemoterapie MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• randomizované kontrolované studie MeSH