BACKGROUND: Dexamethasone 6 mg in patients with severe COVID-19 has been shown to decrease mortality and morbidity. The effects of higher doses of corticosteroid, that would further increase anti-inflammatory effects, are uncertain. The objective of our study was to assess the effect of 20 mg dexamethasone vs. 6 mg dexamethasone intravenously in patients with moderate-to-severe acute respiratory distress syndrome (ARDS) and COVID-19. METHODS: In a multicenter, open-label, randomized trial conducted in nine hospitals in the Czech Republic, we randomized adult patients with ARDS and COVID-19 requiring high-flow oxygen, noninvasive or invasive mechanical ventilation to receive either intravenous high-dose dexamethasone (20 mg/day on days 1-5, 10 mg/day on days 6-10) or standard-dose dexamethasone (6 mg/d, days 1-10). The primary outcome was 28-day ventilator-free days. The five secondary outcomes were 60-day mortality, C-reactive protein dynamics, 14-day WHO (World Health Organization) Clinical Progression Scale score, adverse events and 90-day Barthel index. The long-term outcomes were 180- and 360-day mortality and the Barthel index. The planned sample size was 300, with interim analysis after enrollment of 150 patients. RESULTS: The trial was stopped due to a lack of recruitment, and the follow-up was completed in February 2023. Among 234 randomized patients of 300 planned patients, the primary outcome was available for 224 patients (110 high-dose and 114 standard-dose dexamethasone; median [interquartile range (IQR)] age, 59.0 [48.5-66.0] years; 130 [58.0%] were receiving noninvasive or invasive mechanical ventilation at baseline). The mean number of 28-day ventilator-free days was 8.9 (± 11.5) days for high-dose dexamethasone and 8.0 (± 10.7) days for standard-dose dexamethasone, with an absolute difference of + 0.81 days (95% CI - 2.12-3.73 days). None of the prespecified secondary outcomes, including adverse events, differed between the groups. CONCLUSIONS: Despite not reaching its prespecified enrollment, there was no signal to either benefit or harm high-dose dexamethasone over standard-dose dexamethasone in patients with COVID-19 and moderate-to-severe ARDS. Trial registration Trial registration: ClinicalTrials.gov Identifier: NCT04663555. Registered 10 December 2020, https://clinicaltrials.gov/study/NCT04663555?term=NCT04663555&rank=1 and EudraCT: 2020-005887-70.

• MeSH
• COVID-19 * mortalita   komplikace   MeSH
• dexamethason * aplikace a dávkování   terapeutické užití   MeSH
• farmakoterapie COVID-19 * MeSH
• lidé středního věku MeSH
• lidé MeSH
• SARS-CoV-2 MeSH
• senioři MeSH
• syndrom dechové tísně * farmakoterapie   mortalita   MeSH
• umělé dýchání * MeSH
• výsledek terapie MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• Geografické názvy
• Česká republika MeSH

The International Staging System for multiple myeloma recently underwent a second revision (R2-ISS) to include gain/amplification of 1q21 and account for the additive prognostic significance of multiple high-risk features. The phase 3 ICARIA-MM (isatuximab-pomalidomide-dexamethasone vs. pomalidomide-dexamethasone) and IKEMA (isatuximab-carfilzomib-dexamethasone vs. carfilzomib-dexamethasone) studies provide large datasets for retrospectively validating the prognostic value of the R2-ISS in relapsed/refractory multiple myeloma. Of 609 pooled patients, 68 (11.2%) were reclassified as R2-ISS stage I, 136 (22.3%) as R2-ISS stage II, 204 (33.5%) as R2-ISS stage III, 55 (9.0%) as stage IV, and 146 (24.0%) "Not classified". Median progression-free survival was shorter among those reclassified as R2-ISS stage II (HR 1.52, 95% CI 0.979-2.358), stage III (HR 2.59, 95% CI 1.709-3.923), and stage IV (HR 3.51, 95% CI 2.124-5.784) versus stage I. Adding isatuximab led to longer progression-free survival versus doublet therapy (adjusted HR 0.544 [95% CI 0.436-0.680]), with a consistent treatment effect observed across all R2-ISS stages. This is the first study to validate the R2-ISS with novel agents, including anti-CD38 monoclonal antibodies, and to show that R2-ISS, as a prognostic scoring system, can be applied to patients with relapsed/refractory multiple myeloma.

• MeSH
• dexamethason terapeutické užití   aplikace a dávkování   MeSH
• dospělí MeSH
• humanizované monoklonální protilátky * terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mnohočetný myelom * patologie   farmakoterapie   mortalita   diagnóza   MeSH
• oligopeptidy terapeutické užití   MeSH
• prognóza MeSH
• protokoly antitumorózní kombinované chemoterapie * terapeutické užití   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• staging nádorů * MeSH
• thalidomid analogy a deriváty   terapeutické užití   aplikace a dávkování   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
• validační studie MeSH

Východiska: Idiopatická retroperitoneální fibróza je charakterizovaná rozvojem periaortických a periiliakálních zánětlivých infiltrátů s výraznou fibrózou. Léčba rituximabem v kombinaci s glukokortikoidy je účinná, ale léčebné odpovědi nejsou dlouhodobé. U jiných nemocí byly srovnávány léčebné odpovědi dosahované dvojkombinací rituximab a glukokortikoidy s trojkombinací rituximab, cyklofosfamid a dexametazon, která dosáhla vždy delší a hlubší léčebné odpovědi. A proto jsme ji aplikovali i zde. Případ: Muž, 56 let, přišel s CT obrazem retroperitonální fibrózy s unilaterální okluzí ureteru. Biopsie ložiska prokázala retroperitoneální fibrózu s histologickým nálezem onemocnění asociovaného s IgG4. Léčba prednizonem v dávce 1 mg/kg byla špatně tolerována. Proto byla změněna na trojkombinaci rituximabu 375 mg/m2 v den 1., cyklofosfamidu 300 mg/m2 v infuzi v den 1. a 15. a dexametazonu 20 mg v infuzi v den 1. a 15. v 28denním cyklu. Výsledky: Vyšetření pozitronovou emisní tomografií (PET/CT) s fluorodeoxyglukózou (FDG) po 4. měsíci léčby prokazovalo výrazný pokles akumulace FDG a vymizení fibrotické masy. Léčba trvala 8 měsíců a na ni navázala udržovací léčba, rituximab 1 000 mg a dexametazon 20 mg v 6měsíčních intervalech. Při PET/MR kontrole po 3 letech od zahájení léčby trvá vymizení dříve patrné fibrotické masy (kompletní remise). S aktivitou nemoci koreloval počet cirkulujících plazmablastů v periferní krvi. Závěr: Léčba retroperitonální fibrózy kombinací rituximabu, cyklofosfamidu a dexametazonu dosahuje velmi rychle vymizení patologické akumulace FDG a fibrotické retroperitonální masy již po 4 měsících léčby. Kontrolní PET/MR zobrazení po 3 letech od zahájení léčby potvrdilo kompletní remisi nemoci s vymizením patologické akumulace FDG a s kompletním vymizením dříve zřetelných fibrotických mas. Stále je ale nutná udržovací léčba rituximabem, jak lze odvodit z vzestupu počtu cirkulujích plazmablastů při prodloužení intervalu mezi aplikací rituximabu.

Background: Idiopathic retroperitoneal fibrosis is characterized by the development of inflammatory infiltrates with marked fibrosis along the large retroperitoneal vessels. Rituximab in combination with glucocorticoids constitute an effective therapy, but the responses are not long-lasting. In other similar situations, addition of cyclophosphamide to the combination achieved longer and deeper responses. This was the reason to use the triple combination in this case. Case: A 56-year-old man came with four weeks lasting abdominal pain with CT finding of retroperitoneal fibrosis with unilateral ureteral occlusion. Biopsy confirmed retroperitoneal fibrosis with histological findings of IgG4-associated disease. Treatment with prednizone was poorly tolerated. Therefore, the patient was switched to the combination of rituximab 375 mg/m2 on day 1, cyclophosphamide 300 mg/m2 in infusion in days 1 and 15, plus dexamethasone 20 mg in infusion on days 1 and 15, repeated in a 28-day cycle. Results: Fluorodeoxyglucose (FDG) positron emission tomography (PET/CT) examination after 4 months of treatment showed a marked decrease in FDG accumulation and complete disappearance of the fibrotic mass. After 8 months, the induction therapy was followed by maintenance therapy with rituximab 1,000 mg plus dexamethasone 20 mg in 6-month intervals. Control PET/MR examination after 3 years is consistent with complete remission. The number of circulating plasmablasts correlated with the disease activity. Conclusion: Treatment of retroperitoneal fibrosis with the tripple combination of rituximab, cyclophosphamide and dexamethasone achieved a very rapid disappearance of pathological FDG accumulation and fibrotic retroperitoneal mass, with complete disappearance achieved after 4 months of treatment. After 3 years of maitenance therapy, the diesease is still in complete remission on PET/MR examination. We suggest to continue the maintenance therapy with rituximab because of some increase in the number of circulating plasmablasts after prolongation of the intervals between rituximab administration.

• MeSH
• cyklofosfamid aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• dexamethason aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• fluorodeoxyglukosa F18 farmakologie   terapeutické užití   MeSH
• kombinovaná farmakoterapie * metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• PET/CT metody   MeSH
• retroperitoneální fibróza * diagnostické zobrazování   diagnóza   farmakoterapie   MeSH
• rituximab farmakologie   terapeutické užití   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH
• práce podpořená grantem MeSH

PURPOSE: The use of inotuzumab ozogamicin (InO), a conjugated anti-CD22 monoclonal antibody, is becoming a promising frontline treatment for older patients with ALL. PATIENTS AND METHODS: EWALL-INO is an open-label prospective multicenter phase II trial (ClinicalTrials.gov identifier: NCT03249870). Patients age 55 years and older with newly diagnosed CD22+ Philadelphia chromosome-negative (Ph-) B-cell precursor (BCP) ALL were eligible. After a prephase, a first induction consisting of vincristine, dexamethasone, and three injections of InO (0.8 mg/m2 day 1, 0.5 mg/m2 day 8/day 15) was followed by a second induction combining cyclophosphamide, dexamethasone, and two injections of InO (0.5 mg/m2 day 1/day 8). Responders received up to six cycles of chemotherapy consolidation and 18-month chemotherapy maintenance. Allotransplant was allowed after three consolidations. The primary end point was 1-year overall survival (OS). RESULTS: Between December 2017 and March 2022, 131 patients (median age 68 years) were included. Three patients died during induction 1 (n = 130), two from multiple organ failure and one from hemorrhage, and none during induction 2 (n = 120). After induction 2, 90% of the patients achieved complete remission (CR) or CR with incomplete platelet recovery (CRp) and 80% had measurable residual disease (MRD2) <10-4. Among responders (n = 119), 47 relapsed and 14 died in CR/CRp. One-year OS, relapse-free survival (RFS), and cumulative incidence of relapse (CIR) rates were 73.2%, 66%, and 25%, respectively. High-risk cytogenetics and lower CD22 expression (<70%) were associated with worse OS, while both high-risk cytogenetics and MRD2 ≥10-4 were associated with lower RFS and higher CIR. The 10 allotransplanted patients had very favorable outcomes (90% 2-year OS/RFS and no relapse). Only one nonfatal sinusoidal obstructive syndrome was documented during the study. CONCLUSION: Our results support InO's use in first-line regimens for older patients with CD22+ Ph- BCP-ALL.

• MeSH
• antigeny CD22 * MeSH
• cyklofosfamid aplikace a dávkování   terapeutické užití   MeSH
• dexamethason aplikace a dávkování   terapeutické užití   MeSH
• filadelfský chromozom MeSH
• inotuzumab ozogamicin * terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• pre-B-buněčná leukemie * farmakoterapie   mortalita   genetika   MeSH
• prospektivní studie MeSH
• protokoly antitumorózní kombinované chemoterapie * terapeutické užití   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• vinkristin aplikace a dávkování   terapeutické užití   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 II MeSH
• multicentrická studie MeSH

BACKGROUND: In multiple myeloma (MM), improving our understanding of routine clinical practice and the effectiveness of agents outside of clinical trials is important. TOURMALINE-MM1 data resulted in approval of ixazomib for MM patients who have received ≥ 1 prior therapy. PATIENTS AND METHODS: UVEA-IXA comprised a retrospective chart review in the early access program, and a prospective 1-year follow-up period. Eligible patients had had a biochemical and/or symptomatic relapse after 1-3 prior lines of therapy; no anti-MM therapy for > 3 cycles at the start of ixazomib therapy; and an Eastern Cooperative Oncology Group performance score of 0-2. Lenalidomide- or proteasome inhibitor (PI)-refractory patients were ineligible. Primary endpoints were response and progression-free survival (PFS). RESULTS: Of 357 enrolled patients, 309 were evaluable; most patients received ixazomib alongside lenalidomide (98%) and dexamethasone (97%); 61% had received 2-3 prior lines of therapy. Median PFS was 15.6 months (95% confidence interval [CI]: 12.0-20.6) in all evaluable patients, and 19.6 (95% CI: 12.1-27.0) and 13.9 (95% CI: 10.1-18.1) months in patients who received 1 and ≥ 2 prior lines of therapy, respectively. The overall response rate was 67% in all evaluable patients, and 72% and 63%, respectively, in patients who received 1 and ≥ 2 prior lines of therapy. Median overall survival was 35.5 months. The ixazomib safety profile was consistent with previous reports. CONCLUSION: This study supports ixazomib-based therapy as an effective and tolerable treatment in the real-world. Outcomes were favorable in patients with 1 or ≥ 2 prior lines of therapy who were not lenalidomide- or PI-refractory.

• MeSH
• dexamethason terapeutické užití   MeSH
• glycin analogy a deriváty   MeSH
• lenalidomid terapeutické užití   MeSH
• lidé MeSH
• lokální recidiva nádoru farmakoterapie   MeSH
• mnohočetný myelom * MeSH
• prospektivní studie MeSH
• protokoly antitumorózní kombinované chemoterapie škodlivé účinky   MeSH
• retrospektivní studie MeSH
• sloučeniny boru * MeSH
• uvea MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem 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 antitumorózní 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

WHAT IS THIS SUMMARY ABOUT?: This summary describes the first analysis of the PERSEUS study, which looked at adults with multiple myeloma that had never been treated before, also called newly diagnosed multiple myeloma. Multiple myeloma is a type of cancer in the blood, specifically in plasma cells within the soft, spongy tissue in the center of most bones, called the bone marrow. Researchers wanted to see if adding daratumumab (D) to a standard treatment of three other medicines called VRd, which stands for bortezomib (V), lenalidomide (R), and dexamethasone (d), could stop the multiple myeloma from getting worse and help participants live longer without multiple myeloma.Half of the participants were assigned to the treatment plan with daratumumab; they received D-VRd during initial treatment phases (induction and consolidation), followed by daratumumab as well as lenalidomide (D-R) in the maintenance phase. The other half of participants received treatment without daratumumab; they received VRd induction and consolidation followed by lenalidomide alone (R) maintenance. In addition, all participants were able to receive an autologous stem cell transplant, a procedure used to further help reduce multiple myeloma. WHAT WERE THE RESULTS?: At the time of this analysis of PERSEUS, about 4 years after participants started the study, participants who received D-VRd treatment followed by D-R maintenance had a better response to treatment (as measured by specific markers of multiple myeloma) and were more likely to be alive and free from their multiple myeloma getting worse in comparison to participants who received VRd followed by R maintenance. Side effects (unwanted or undesirable effects of treatment) in both treatment groups were in line with the known side effects of daratumumab and VRd. WHAT DO THE RESULTS MEAN?: The results of the PERSEUS study showed that including daratumumab in D-VRd induction/consolidation and D-R maintenance was better for treating multiple myeloma than the current standard VRd treatment followed by R maintenance alone in adults with a new diagnosis of multiple myeloma who were also able to receive an autologous stem cell transplant. Of importance, there were no unexpected side effects in either group.Clinical Trial Registration: NCT02874742 (GRIFFIN) (ClinicalTrials.gov).

• MeSH
• bortezomib * aplikace a dávkování   terapeutické užití   MeSH
• dexamethason * aplikace a dávkování   terapeutické užití   MeSH
• dospělí MeSH
• klinické zkoušky, fáze II jako téma MeSH
• lenalidomid * aplikace a dávkování   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mnohočetný myelom * farmakoterapie   diagnóza   MeSH
• monoklonální protilátky * aplikace a dávkování   terapeutické užití   MeSH
• protokoly antitumorózní kombinované chemoterapie * terapeutické užití   škodlivé účinky   MeSH
• randomizované kontrolované studie jako téma MeSH
• senioři 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
• informační letáky pro pacienty MeSH

We performed retrospective analysis of relapsed/refractory multiple myeloma (RRMM) patients previously exposed to daratumumab treated with ixazomib, lenalidomide, dexamethasone (IRd) regimen in real clinical practice. Our aim was to evaluate efficacy of IRd in these patients and select a subset of patients that would benefit from this treatment the most. In total, we analyzed 43 daratumumab-exposed RRMM patients treated in our center. Minimal response or better was achieved by 53.5% of patients from the cohort. Median progression free survival (PFS) was 4.56 months (95% CI: 2.56, 8.03) and median overall survival (OS) was 28.92 months (95% CI: 5.4, NR). Duration of response (DOR) was evaluable in 28 patients and reached a median of 21.3 months (95% CI: 6.85, NR). Next, we evaluated hazard ratios (HR) for OS and PFS. There was improved OS in patients that were not-triple refractory or worse (HR = 0.39, 95%Cl (0.14; 1.10), p = .07) and in patients, that had less than three previous lines of treatment (LOT) (HR = 0.13, 95%Cl (0.03; 0.6) p = .003). Similar to OS, there was improved PFS in patients, that were not triple-refractory or worse (HR = 0.52, 95%Cl (0.25; 1.10), p = .08). We concluded, that the best survival benefit for RRMM patients pretreated with daratumumab to IRd regimen was observed in patients that were not triple-refractory and had less than three previous lines of treatment (LOT). The DOR in these patients was 21.3 months (95% CI: 6.85, NR).

• MeSH
• chemorezistence * MeSH
• dexamethason * aplikace a dávkování   terapeutické užití   MeSH
• dospělí MeSH
• glycin * analogy a deriváty   aplikace a dávkování   terapeutické užití   MeSH
• lenalidomid * aplikace a dávkování   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mnohočetný myelom * farmakoterapie   mortalita   MeSH
• monoklonální protilátky * terapeutické užití   aplikace a dávkování   MeSH
• opakovaná terapie MeSH
• protokoly antitumorózní kombinované chemoterapie * terapeutické užití   škodlivé účinky   MeSH
• recidiva MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• sloučeniny boru * aplikace a dávkování   terapeutické užití   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

• MeSH
• COVID-19 * mortalita   komplikace   MeSH
• dexamethason * terapeutické užití   MeSH
• dospělí MeSH
• farmakoterapie COVID-19 * MeSH
• hematologické nádory * mortalita   farmakoterapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• registrace * MeSH
• SARS-CoV-2 * izolace a purifikace   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
• dopisy MeSH
• práce podpořená grantem MeSH

BACKGROUND: Isatuximab is an anti-CD38 monoclonal antibody approved for the treatment of relapsed or refractory multiple myeloma. Previous analyses of the IKEMA trial showed prolonged progression-free survival in patients with this disease who received isatuximab in combination with carfilzomib-dexamethasone as compared with those who received carfilzomib-dexamethasone alone. Herein, we report the analysis of overall survival from the IKEMA trial. METHODS: This prospective, randomised, open-label, active-controlled, phase 3 study included patients with relapsed or refractory multiple myeloma aged 18 years or older, who had received one to three previous lines of treatment from 69 study centres in 16 countries across North America, South America, Europe, and the Asia-Pacific region. Patients were randomly allocated (3:2) to treatment with either isatuximab plus carfilzomib-dexamethasone (isatuximab group) or carfilzomib-dexamethasone (control group). In the isatuximab group, patients received intravenous isatuximab (10 mg/kg on days 1, 8, 15, and 22 of the first 28-day cycle, and days 1 and 15 of subsequent 28-day cycles). In both treatment groups, intravenous carfilzomib (20 mg/m2 on days 1 and 2 of the first cycle; and 56 mg/m2 on days 8, 9, 15, and 16 of the first cycle, and days 1, 2, 8, 9, 15, and 16 of subsequent cycles) and intravenous or oral dexamethasone (20 mg on days 1, 2, 8, 9, 15, 16, 22, and 23) were administered. The primary endpoint of the trial was progression-free survival, which was reported previously. Treatment continued until progression, unacceptable toxicity, or patient request to discontine. The overall survival analysis reported here was planned to be conducted 3 years after the primary progression-free survival analysis in the intention-to-treat population. Additional analyses were conducted on the secondary endpoints of time to next treatment and second-progression-free survival. Reported p values are non-inferential due to hierarchical testing. This trial is registered with ClinicalTrials.gov (NCT03275285). FINDINGS: Between Nov 15, 2017, and March 21, 2019, 302 patients were enrolled and randomly allocated: 179 (59%) to the isatuximab group and 123 (41%) to the control group. 169 (56%) patients were male, 133 (44%) were female, 214 (71%) were White, 50 (17%) were Asian, nine (3%) were Black or African American, and three (1%) were multiracial. At data cutoff for this overall survival analysis (Feb 7, 2023), 79 (44%) overall survival events in the isatuximab group and 59 (48%) in the control group had occurred (median follow-up 56·61 months [IQR 54·90-58·02]). Median overall survival (in months) was not reached (NR; 95% CI 52·17-NR) in the isatuximab group and was 50·60 months (38·93-NR) in the control group (hazard ratio [HR] 0·855 [95% CI 0·608-1·202], nominal one-sided p=0·18). Survival probability at 48 months was 59·7% (95% CI 52·0-66·7) in the isatuximab group and 52·2% (95% CI 42·7-60·8) in the control group (based on Kaplan-Meier analysis). Improvements in time to next treatment (HR 0·583 [95% CI 0·429-0·792], nominal one-sided p=0·0002) and second-progression-free survival (0·663 [0·491-0·895], nominal one-sided p=0·0035) were observed in the isatuximab group. The most common treatment-emergent adverse events were infusion reactions (82 [46%] patients in the isatuximab group and four [3%] in the control group) and upper respiratory tract infections (71 [40%] and 34 [28%], respectively). Discontinuations due to treatment-emergent adverse events were similar between treatment groups (24 [14%] in the isatuximab group and 22 [18%] in the control group), despite an additional 30 weeks of exposure in the isatuximab group. 12 (7%) patients in the isatuximab group and six (5%) patients in the control group had a treatment-related adverse event with a fatal outcome during study treatment. INTERPRETATION: At the time of the current analysis, a difference in overall survival could not be detected between the treatment groups, and no new safety signals were observed. Collectively, the evidence suggests that isatuximab plus carfilzomib-dexamethasone is a key treatment for patients with relapsed or refractory multiple myeloma. FUNDING: Sanofi.

• MeSH
• analýza přežití MeSH
• dexamethason * aplikace a dávkování   terapeutické užití   MeSH
• doba přežití bez progrese choroby MeSH
• dospělí MeSH
• humanizované monoklonální protilátky * terapeutické užití   aplikace a dávkování   škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru farmakoterapie   mortalita   MeSH
• mnohočetný myelom * farmakoterapie   mortalita   MeSH
• oligopeptidy * terapeutické užití   aplikace a dávkování   MeSH
• prospektivní studie MeSH
• protokoly antitumorózní kombinované chemoterapie * terapeutické užití   MeSH
• senioři 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
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH