No data are available regarding obesity and outcome in Chronic Lymphocytic Leukemia (CLL). We analyzed 263 patients from the AGMT CLL-8a Mabtenance trial for the impact of obesity. The trial included patients after rituximab-containing induction treatment in first or second line that had achieved at least a PR. A randomization to rituximab maintenance treatment (375 mg/m2 q3 months for 2 years) vs observation was performed. In this cohort 22% of the patients (58/263) were classified as obese. The baseline response to induction treatment was inferior in obese patients with a lower CR rate (43.1% vs 60.5% in obese vs non-obese, P = 0.018) and with a lower rate of patients achieving MRD negativity after chemoimmunotherapy induction treatment (19.6% vs 35.8%, P = 0.02). The PFS outcome of obese patients was significantly worse in the observation group of the trial (24 vs 39 months median PFS, P = 0.03). However, in the rituximab maintenance group the outcome for obese vs non-obese was not different (P = 0.4). In summary, obesity was overall associated with a worse outcome of chemoimmunotherapy induction. However, rituximab maintenance treatment seems to be able to overcome this negative effect.
- MeSH
- analýza přežití MeSH
- chronická lymfatická leukemie farmakoterapie mortalita MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- obezita komplikace mortalita MeSH
- prognóza MeSH
- rituximab aplikace a dávkování terapeutické užití MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- udržovací chemoterapie 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
- randomizované kontrolované studie MeSH
Lenalidomide (LEN) is an immunomodulator with clinical activity against myeloma cells. Based on the pivotal phase 3 trials MM-009 and MM010, the combination of lenalidomide and dexamethasone(DEX) was approved for patients with multiple myeloma who received at least one prior therapy. Here, we evaluated LEN/DEX therapy in unselected population and subsequently in selected sub-groups of patients with relapsed/refractory multiple myeloma followed in the Registry of Monoclonal Gammopathies of the Czech Myeloma Group. Altogether 858 patients were treated with LEN/DEX in the Czech Republic and Slovakia until end of 2017. The analyzed sub-groups were defined as patients with high risk cytogenetic aberrations and patients with relapsed and refractory MM. The overall response rate (ORR; partial remission or better response, PR) in the whole group of patients was 46.3% for all lines of therapy, 26.4% for high-risk group and 32.1% for relapsed and refractory group. Medians of overall survival (OS) in the same cohorts were as follows: 25.6, 15.7 and 18.5 months, progression free survival (PFS) was: 11.2, 6.4 and 9.0 months respectively. The most common adverse events were hematologic and infectious. In conclusion we found that our results correlated with those found in other studies in terms of response rates, survival measures, and also of treatment toxicity.
- MeSH
- analýza přežití MeSH
- antitumorózní látky škodlivé účinky terapeutické užití MeSH
- dexamethason * škodlivé účinky terapeutické užití MeSH
- lenalidomid * škodlivé účinky terapeutické užití MeSH
- lidé MeSH
- mnohočetný myelom * farmakoterapie mortalita MeSH
- protokoly antitumorózní kombinované chemoterapie MeSH
- registrace * statistika a číselné údaje MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
- Slovenská republika MeSH
Prvé skúsenosti s liečbou pacientov s mnohopočetným myelómom pomalidomidom na Slovensku. Farmakoterapie 2017;13(2):198–204. Pacienti s mnohopočetným myelómom refraktérni voči bortezomibu a lenalidomidu mali donedávna veľmi obmedzené možnosti ďalšej liečby a zlú prognózu. V auguste 2013 schválila Európska agentúra pre lieky (EMA) imunomodulačný liek druhej generácie pomalidomid, indikovaný v kombinácii s dexametazónom na liečbu dospelých pacientov s relabujúcim-refraktérnym mnohopočetným myelómom (RRMM), ktorí sa predtým podrobili najmenej dvom terapeutickým režimom, zahŕňajúcim ako lenalidomid, tak aj bortezomib a pri poslednej liečbe preukázali progresiu ochorenia. Na Slovensku zatiaľ nie je pomalidomid zaradený do zoznamu uhrádzaných liekov, a preto skúsenosti s jeho použitím sú obmedzené. Predstavujeme výsledky liečby pacientov z centier v Bratislave, Nitre, Martine a Košiciach v období jún 2014 až marec 2017. Celkový počet pacientov bol 23, dostatočné údaje pre vyhodnotenie sme získali od 21 pacientov. Z nich bolo 7 liečených na základe mimoriadneho schválenia úhrady lieku (podľa § 88 zákona č. 363/2011) a 14 pacientom poskytla liek spoločnosť Celgene. Medián veku bol 64 (rozsah 44–76). Pacienti boli intenzívne predliečení, medián počtu predchádzajúcich línií lieč- by bol 4 (3–10), 100 % pacientov bolo refraktérnych voči lenalidomidu. Liečbu pomalidomidom v kombinácii s dexametazónom sme začali u každého pacienta v dávke 4 mg 1.–21. deň 28-dňového cyklu. Dosiahnuté liečebné odpovede boli nasledovné: celková miera odpovedí (ORR) n = 14 (67 %), veľmi dobrá parciálna odpoveď (VGPR) n = 6 (29 %), parciálna odpoveď (PR) n = 8 (38 %), minimálna odpoveď (MR) n = 1 (5 %). Kompletnú remisiu (CR) nedosiahol ani jeden pacient. Stabilné ochorenie (SD) sa zaznamenalo u 6 pacientov (29 %). Medián počtu podaných cyklov bol 8 (3–28), medián trvania liečby bol 10 mesiacov (3–34). Pri mediáne sledovania 16 mesiacov bol medián prežívania bez progresie (PFS) 13,0 mesiacov (95% CI: 5,9–20,1). Medián celkového prežívania (OS) nebol dosiahnutý. Nežiaduce účinky boli očakávané, aj v prípade vyššieho stupňa úspešne zvládnuté úpravou liečebného režimu a podpornou medikáciou. Ani v jednom prípade neviedli k predčasnému ukončeniu liečby pomalidomidom. Pacienti v našom súbore mali porovnateľné charakteristiky s pacientmi v registračnej štúdii pre pomalidomid MM-003, zaznamenali sme vyšší počet podaných cyklov, vyššiu mieru odpovedí a dlhší PFS, k čomu mohol prispieť starostlivý vý- ber pacientov. Vzhľadom na obmedzenú dostupnosť pomalidomidu sme indikovali pacientov v dobrom výkonnostnom stave s predpokladom úspešnej liečby. Navyše 6 pacientov malo pre nedostatočný účinok v priebehu liečby pridaný tretí liek do kombinácie. Treba podotknúť, že u týchto ťažko predliečených pacientov aj dosiahnutie SD prinieslo benefit vo forme kontroly ochorenia pri dobrej kvalite života.
Multiple myeloma patients refractory to both bortezomib and lenalidomide had until recently limited therapeutic options and poor prognosis. Pomalidomide, a second generation immunomodulatory agent, was approved by the European Medicines Agency (EMA) in August 2013 for patients with relapsed and refractory multiple myeloma who have received at least two prior therapies including lenalidomide and bortezomib and have progressed on their last therapy. Pomalidomide has not yet been included in the list of reimbursed drugs in Slovakia, therefore experience with its use is very limited. We present the results of pomalidomide treatment in patients from Slovak centres in Bratislava, Nitra, Martin and Košice in the period June 2014– March 2017th. The total number of patients was 23, sufficient data for evaluation we obtained from 21 patients. Seven patients were treated based on exceptional reimbursement approval (in accordance with § 88 of Act no. 363/2011). 14 patients were treated with Celgene provided pomalidomide. Median age was 64 years (range 44–76). Patients were heavily pretreated, the median of prior lines therapy was 4 (range 3–10), 100% of patients were refractory to lenalidomide. Initial dose of pomalidomide was 4 mg daily, D1–D21 in 28-days cycles, administered in combination with dexamethasone. Overall response rate was n=14 (67 %), no patients achieved complete remission, 6 pts (29%) achieved very good partial response, 8 pts (38%) partial response, 1 patient (5%) minimal response. Stable disease was reported in 6 patients (29%). Median of treatment cycles administered was 8 (3–28), median treatment duration was 10 months (3–34). At the median follow up of 16 months, median progression free survival (PFS) was 13,0 months (95% CI 5,9–21). Median overall survival was not reached. Adverse events (AEs) were predictable, manageable with dose adjustment and supportive treatment. AEs did not lead to premature discontinuation of treatment. Patients characteristics in our group were comparable with those from the registration trial MM-003. Higher response rate, higher median of cycles administered, longer PFS were observed in our group compared to registration trial MM-003. This may be due to strict patient´s selection in condition of limited drug access. Moreover, 6 patients had third drug added in the combination during treatment due to lack of efficacy. In these heavily pretreated patients achieving SD also bring benefits in the form of disease control with good quality of life.
- MeSH
- analýza přežití MeSH
- imunologické faktory aplikace a dávkování farmakologie MeSH
- inhibitory angiogeneze terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- mnohočetný myelom * diagnóza farmakoterapie MeSH
- nežádoucí účinky léčiv epidemiologie MeSH
- přežití po terapii bez příznaků nemoci MeSH
- senioři MeSH
- thalidomid analogy a deriváty aplikace a dávkování farmakologie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
BACKGROUND: In many patients with chronic lymphocytic leukaemia requiring treatment, induction therapy with rituximab plus chemotherapy improves outcomes compared with chemotherapy alone. In this study we aimed to investigate the potential of rituximab maintenance therapy to prolong disease control in patients who respond to rituximab-containing induction regimens. METHODS: In this randomised, international, multicentre, open-label, phase 3 clinical trial, we enrolled patients who had achieved a complete response (CR), CR with incomplete bone marrow recovery (CRi), or partial response (PR) to first-line or second-line rituximab-containing chemoimmunotherapy and randomly assigned them in a 1:1 ratio (central block randomisation in the electronic case report form system) to either intravenous rituximab 375 mg/m(2) every 3 months, or observation alone, for 2 years. Stratification was by country, line of treatment, type of chemotherapy added to the rituximab backbone, and degree of remission following induction. The primary endpoint was progression-free survival. Efficacy analysis was done in the intention-to-treat population. This is the final, event-triggered analysis. Final analysis was triggered by the occurrence of 92 events. This trial is registered with ClinicalTrials.gov, number NCT01118234. FINDINGS: Between April 1, 2010, and Dec 23, 2013, 134 patients were randomised to rituximab and 129 to observation alone. Median observation times were 33·4 months (IQR 25·7-42·8) for the rituximab group and 34·0 months (25·4-41·9) for the observation group. Progression-free survival was significantly longer in the rituximab maintenance group (47·0 months, IQR 28·5-incalculable) than with observation alone (35·5 months, 95% CI 25·7-46·3; hazard ratio [HR] 0·50, 95% CI 0·33-0·75, p=0·00077). The incidence of grade 3-4 haematological toxicities other than neutropenia was similar in the two treatment groups. Grade 3-4 neutropenia occurred in 28 (21%) patients in the rituximab group and 14 (11%) patients in the observation group. Apart from neutropenia, the most common grade 3-4 adverse events were upper (five vs one [1%] patient in the observation group) and lower (three [2%] vs one [1%]) respiratory tract infection, pneumonia (nine [7%] vs two [2%]), thrombopenia (four [3%] vs four [3%]), neoplasms (five [4%] vs four [3%]), and eye disorders (four [3%] vs two [2%]). The overall incidence of infections of all grades was higher among rituximab recipients (88 [66%] vs 65 [50%]). INTERPRETATION: Rituximab maintenance therapy prolongs progression-free survival in patients achieving at least a PR to induction with rituximab plus chemotherapy, and the treatment is well tolerated overall. Although it is associated with an increase in infections, there is no excess in infection mortality, suggesting that remission maintenance with rituximab is an effective and safe option in the management of chronic lymphocytic leukaemia in early treatment phases. FUNDING: Arbeitsgemeinschaft Medikamentöse Tumortherapie gemeinnützige GmbH (AGMT), Roche.
- MeSH
- bendamustin hydrochlorid aplikace a dávkování MeSH
- chronická lymfatická leukemie farmakoterapie patologie patofyziologie MeSH
- cyklofosfamid aplikace a dávkování MeSH
- dospělí MeSH
- imunoterapie * MeSH
- indukce remise MeSH
- lidé středního věku MeSH
- lidé MeSH
- míra přežití MeSH
- protokoly antitumorózní kombinované chemoterapie aplikace a dávkování terapeutické užití MeSH
- rituximab aplikace a dávkování MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- staging nádorů MeSH
- vidarabin aplikace a dávkování analogy a deriváty 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
- srovnávací studie MeSH
Mnohopočetný myelóm (MM) je nádorové ochorenie, ktoré vzniká nekontrolovanou proliferáciou a akumuláciou neoplasticky transformovaných elementov ß-bunkovej línie charakteru plazmocytov, sprevádzané produkciou M-proteínu („paraproteínu“ dokázateľného v sére a/alebo v moči s prejavmi orgánovej dysfunkcie – CRAB). Aj keď súčasné liečebné stratégie so zavedením nových liekov predĺžili prežívanie a významne zlepšili kvalitu života chorých, zostáva aj naďalej nevyliečiteľným ochorením. Štandardom liečby u pacientov do 65 rokov bez závažnej sprievodnej komorbidity zostáva chemoterapia s následnou autológnou transplantáciou periférnych kmeňových buniek, ktorou dosahujeme vyšší počet kompletných remisií (25-50 %) ako konvenčnou chemoterapiou. U starších pacientov nad 65 rokov a mladších nevhodných na transplantáciu sa v úvode podáva kombinovaná chemoterapia so zaradením nových liekov (bortezomib, talidomid, lenalidomid).
Multiple myeloma (MM) is a neoplasia that arises from an uncontrolled proliferation and accumulation of the neoplastic transformed ß-cell line with the characteristics of plasmocytes accompanied by the production of M-protein („paraprotein“ detectable in the blood and/or urine) and sings of the organ dysfunction (CRAB). Although current treatment strategies with novel agents significantly prolonged survival and improved quality of life of patients, remains MM an incurable disease. The standard of care for patients under 65 years without major attendant comorbidity remains chemotherapy followed by autologous peripheral stem cells transplantation; so we achieved a higher number of complete responses (25-50 %) vs. conventional chemotherapy alone. Elderly patients over 65 years and younger patients unsuitable for transplantation have induction chemotherapy with inclusion of novel agents (bortezomib, thalidomide, lenalidomide).
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
