CONTEXT: R/R FL is associated with a poor prognosis and remains incurable; thus, better treatment options are needed. Epcoritamab is a subcutaneously administered CD3xCD20 bispecific antibody that has shown substantial antitumor activity in R/R FL. OBJECTIVE: Evaluate safety and efficacy of epcoritamab with R2 in patients with R/R FL in arm 2 of a phase 1/2 open-label trial (EPCORE NHL-2; NCT04663347). PATIENTS: Adults with R/R CD20+ FL were included. As of December 1, 2021, 30 patients (median age, 68 y) had enrolled. INTERVENTIONS: Patients received subcutaneous epcoritamab (QW, cycle [C] 1-3; Q2W, C4-9; Q4W, C≥10 up to 2 y) + R2 for 12 cycles of 28 d. Step-up dosing and corticosteroid prophylaxis were required. RESULTS: Of the 30 patients (epcoritamab 24 mg, n=3; 48 mg, n=27), 21 (70%) had stage IV disease and 20 (67%) had FLIPI scores 3-5. Median (range) number of prior lines of therapy was 1 (1-5), 30% had primary refractory disease, and 40% had disease progression within 24 mo after starting first-line treatment. At a median (range) follow-up of 5.1 mo (0.8-12.3), 25 patients (83%) remained on treatment; 5 patients discontinued treatment due to progression (n=2), AEs (n=2), or consent withdrawal (n=1). Common treatment-emergent AEs (TEAEs) of any grade (G) included infections (57%), injection-site reactions (50%), constipation (37%), fatigue (37%), and neutropenia (37%). CRS events occurred in 15 patients (50%; G1-2 43%, G3 7%), primarily in C1. All CRS events resolved; 3 patients were treated with tocilizumab, and 1 patient discontinued treatment due to CRS. One patient experienced G2 ICANS. No fatal TEAEs occurred. Overall response rate for the 27 evaluable patients was 100%; 93% had a complete metabolic response (CMR) and 7% had a partial metabolic response by PET-CT. As of the data cut, the longest duration of response was 7.0+ mo and ongoing. CONCLUSIONS: Subcutaneous epcoritamab + R2 exhibits promising efficacy, including a high CMR rate, in patients with R/R FL. The safety profile was consistent with prior data. Updated data will be presented. FUNDING: This study was funded by Genmab A/S and AbbVie.

• MeSH
• dospělí MeSH
• folikulární lymfom * farmakoterapie   patologie   MeSH
• lenalidomid terapeutické užití   MeSH
• lidé MeSH
• PET/CT MeSH
• protilátky bispecifické terapeutické užití   MeSH
• protokoly antitumorózní kombinované chemoterapie * škodlivé účinky   MeSH
• rituximab terapeutické užití   MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze I MeSH
• klinické zkoušky, fáze II MeSH

Tafasitamab (MOR208), an Fc-modified, humanized, anti-CD19 monoclonal antibody, combined with the immunomodulatory drug lenalidomide was clinically active with a good tolerability profile in the open-label, single-arm, phase II L-MIND study of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) ineligible for autologous stem-cell transplantation. To assess long-term outcomes, we report an updated analysis with ≥35 months' follow-up. Patients were aged >18 years, had received one to three prior systemic therapies (including ≥1 CD20-targeting regimen) and Eastern Cooperative Oncology Group performance status 0-2. Patients received 28-day cycles of tafasitamab (12 mg/kg intravenously), once weekly during cycles 1-3, then every 2 weeks during cycles 4-12. Lenalidomide (25 mg orally) was administered on days 1-21 of cycles 1-12. After cycle 12, progression-free patients received tafasitamab every 2 weeks until disease progression. The primary endpoint was best objective response rate. After ≥35 months' follow-up (data cut-off: October 30, 2020), the objective response rate was 57.5% (n=46/80), including a complete response in 40.0% of patients (n=32/80) and a partial response in 17.5% of patients (n=14/80). The median duration of response was 43.9 months (95% confidence interval [95% CI]: 26.1-not reached), the median overall survival was 33.5 months (95% CI: 18.3-not reached) and the median progression-free survival was 11.6 months (95% CI: 6.3-45.7). There were no unexpected toxicities. Subgroup analyses revealed consistent long-term efficacy results across most subgroups of patients. This extended follow-up of L-MIND confirms the long duration of response, meaningful overall survival, and well-defined safety profile of tafasitamab plus lenalidomide followed by tafasitamab monotherapy in patients with relapsed/refractory diffuse large B-cell lymphoma ineligible for autologous stem cell transplantation. ClinicalTrials.gov identifier: NCT02399085.

• MeSH
• autologní transplantace MeSH
• difúzní velkobuněčný B-lymfom * diagnóza   farmakoterapie   MeSH
• humanizované monoklonální protilátky MeSH
• lenalidomid terapeutické užití   MeSH
• lidé MeSH
• protokoly antitumorózní kombinované chemoterapie škodlivé účinky   MeSH
• transplantace hematopoetických kmenových buněk * MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• práce podpořená grantem MeSH

The phase 2 CAVALLI (NCT02055820) study assessed efficacy and safety of venetoclax, a selective B-cell lymphoma-2 (Bcl-2) inhibitor, with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in first-line (1L) diffuse large B-cell lymphoma (DLBCL), including patients demonstrating Bcl-2 protein overexpression by immunohistochemistry (Bcl-2 IHC+). Eligible patients were ≥18 years of age and had previously untreated DLBCL, Eastern Cooperative Oncology Group performance status ≤2, and International Prognostic Index 2 to 5. Venetoclax 800 mg (days 4-10, cycle 1; days 1-10, cycles 2-8) was administered with rituximab (8 cycles) and cyclophosphamide, doxorubicin, vincristine, and prednisone (6-8 cycles) in 21-day cycles. Primary end points were safety, tolerability, and research_plete response (CR) at end of treatment (EOT). Secondary end points were progression-free survival (PFS) and overall survival. Comparative analyses used covariate-adjusted R-CHOP controls from the GOYA/BO21005 study, an appropriate contemporary benchmark for safety and efficacy. Safety and efficacy analyses included 206 patients. CR rate at EOT was 69% in the overall population and was maintained across Bcl-2 IHC+ subgroups. With a median follow-up of 32.2 months, trends were observed for improved investigator-assessed PFS for venetoclax plus R-CHOP in the overall population (hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.43-0.87) and Bcl-2 IHC+ subgroups (HR, 0.55; 95% CI, 0.34-0.89) vs R-CHOP. Despite a higher incidence of grade 3/4 hematologic adverse events (86%), related mortality was not increased (2%). Chemotherapy dose intensity was similar in CAVALLI vs GOYA. The addition of venetoclax to R-CHOP in 1L DLBCL demonstrates increased, but manageable, myelosuppression and the potential of improved efficacy, particularly in high-risk Bcl-2 IHC+ patient subgroups.

• MeSH
• bicyklické sloučeniny heterocyklické aplikace a dávkování   škodlivé účinky   MeSH
• cyklofosfamid aplikace a dávkování   škodlivé účinky   MeSH
• difúzní velkobuněčný B-lymfom farmakoterapie   genetika   MeSH
• dospělí MeSH
• doxorubicin aplikace a dávkování   škodlivé účinky   MeSH
• faktor stimulující kolonie granulocytů terapeutické užití   MeSH
• gastrointestinální nemoci chemicky indukované   MeSH
• geny bcl-2 MeSH
• infekce etiologie   MeSH
• Kaplanův-Meierův odhad MeSH
• krevní nemoci chemicky indukované   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nádorové proteiny antagonisté a inhibitory   MeSH
• prednison aplikace a dávkování   škodlivé účinky   MeSH
• protokoly antitumorózní kombinované chemoterapie aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• protoonkogenní proteiny c-bcl-2 antagonisté a inhibitory   MeSH
• rituximab aplikace a dávkování   škodlivé účinky   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• sulfonamidy aplikace a dávkování   škodlivé účinky   MeSH
• únava chemicky indukované   MeSH
• vinkristin aplikace a dávkování   škodlivé účinky   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze I MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

PURPOSE: Indolent non-Hodgkin lymphoma (iNHL) remains largely incurable and often requires multiple lines of treatment after becoming refractory to standard therapies. Duvelisib was approved by the Food and Drug Administration for relapsed or refractory (RR) chronic lymphocytic leukemia or small lymphocytic lymphoma (SLL) and RR follicular lymphoma (FL) after two or more prior systemic therapies. On the basis of the activity of duvelisib, a first-in-class oral dual inhibitor of phosphoinositide 3-kinase-δ,-γ, in RR iNHL in a phase I study, the safety and efficacy of duvelisib monotherapy was evaluated in iNHL refractory to rituximab and either chemotherapy or radioimmunotherapy. PATIENTS AND METHODS: Eligible patients had measurable iNHL (FL, SLL, or marginal zone B-cell lymphoma) double refractory to rituximab (monotherapy or in combination) and to either chemotherapy or radioimmunotherapy. All were treated with duvelisib 25 mg orally twice daily in 28-day cycles until progression, unacceptable toxicity, or death. The primary end point was overall response rate (ORR) using the revised International Working Group criteria for malignant lymphoma. RESULTS: This open-label, global phase II trial enrolled 129 patients (median age, 65 years; median of three prior lines of therapy) with an ORR of 47.3% (SLL, 67.9%; FL, 42.2%; MZL, 38.9%). The estimated median duration of response was 10 months, and the estimated median progression-free survival was 9.5 months. The most frequent any-grade treatment-emergent adverse events (TEAEs) were diarrhea (48.8%), nausea (29.5%), neutropenia (28.7%), fatigue (27.9%), and cough (27.1%). Among the 88.4% of patients with at least one grade 3 or greater TEAE, the most common TEAEs were neutropenia (24.8%), diarrhea (14.7%), anemia (14.7%), and thrombocytopenia (11.6%). CONCLUSION: In the DYNAMO study, oral duvelisib monotherapy demonstrated clinically meaningful activity and a manageable safety profile in heavily pretreated, double-refractory iNHL, consistent with previous observations. Duvelisib may provide a new oral treatment option for this patient population of which many are elderly and in need of additional therapies.

• MeSH
• antiflogistika nesteroidní škodlivé účinky   terapeutické užití   MeSH
• aplikace orální MeSH
• chemorezistence účinky léků   MeSH
• dospělí MeSH
• fosfatidylinositol-3-kinasy metabolismus   MeSH
• inhibitory enzymů aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• isochinoliny aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• Kaplanův-Meierův odhad MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru MeSH
• nehodgkinský lymfom farmakoterapie   patologie   MeSH
• protokoly antitumorózní kombinované chemoterapie terapeutické užití   MeSH
• průjem chemicky indukované   MeSH
• puriny aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• rituximab aplikace a dávkování   MeSH
• rozvrh dávkování léků 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 II MeSH
• práce podpořená grantem MeSH

BACKGROUND: Chronic rhinosinusitis (CRS) is a chronic inflammatory disease associated with a substantial personal and socioeconomic burden. Monitoring of patient-reported outcomes by mobile technology offers the possibility to better understand real-life burden of CRS. METHODS: This study reports on the cross-sectional evaluation of data of 626 users of mySinusitisCoach (mSC), a mobile application for CRS patients. Patient characteristics of mSC users were analysed as well as the level of disease control based on VAS global rhinosinusitis symptom score and adapted EPOS criteria. RESULTS: The mSC cohort represents a heterogeneous group of CRS patients with a diverse pattern of major symptoms. Approximately half of patients reported nasal polyps. 47.3% of all CRS patients were uncontrolled based on evaluation of VAS global rhinosinusitis symptom score compared to 40.9% based on adapted EPOS criteria. The impact of CRS on sleep quality and daily life activities was significantly higher in uncontrolled versus well-controlled patients. Half of patients had a history of FESS (functional endoscopic sinus surgery) and reported lower symptom severity compared to patients without a history of FESS, except for patients with a history of more than 3 procedures. Patients with a history of FESS reported higher VAS levels for impaired smell. CONCLUSION: Real-life data confirm the high disease burden in uncontrolled CRS patients, clearly impacting quality of life. Sinus surgery improves patient-reported outcomes, but not in patients with a history of more than 3 procedures. Mobile technology opens a new era of real-life monitoring, supporting the evolution of care towards precision medicine.

• MeSH
• chronická nemoc MeSH
• kvalita života MeSH
• lidé MeSH
• nosní polypy * epidemiologie   MeSH
• průřezové studie MeSH
• rinitida * diagnóza   epidemiologie   MeSH
• sinusitida * diagnóza   epidemiologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• biodiverzita * MeSH
• zachování přírodních zdrojů * MeSH
• Publikační typ
• časopisecké články MeSH
• komentáře MeSH