The increase in melanoma incidence makes oncology patient pathway management for melanoma patients a priority. The aim of this publication is to present the oncological care of patients with melanoma in Hungary’s first oncology patient pathway management system. The OnkoNetwork system was developed and implemented in 2015 in Moritz Kaposi General Hospital in Somogy County, where the authors followed the care of 670 patients with melanoma among thousands of oncology patients. The system monitored the process and time management of melanoma patients’ care from the time of suspicion to the time of closure. The diagnosis, oncological treatment and follow-up of patients are governed by standardized protocols. The system ensures that patients are seen and diagnosed within 21 days. The Oncoteam, within 30 days of entering the system, decides on the patient’s further investigation and treatment, and treatment starts within 14 days of the Oncoteam’s decision. The importance of the OnkoNetwork system is, first and foremost, to provide uniform, protocol-driven care, redirect “lost” patients and reduce delays due to anomalies in the healthcare system. With the use of a patient pathway management system, the diagnosis, treatment and follow-up of melanoma patients are prioritized.
7017 Background: The phase 3 SYMPATICO study evaluated ibrutinib (Ibr) combined with venetoclax (Ven) in 3 cohorts of patients (pts) with MCL: an open-label safety run-in phase to evaluate concurrent initiation of Ibr+Ven in relapsed/refractory (R/R) MCL; a randomized phase to evaluate Ibr+Ven vs Ibr+placebo (Pbo) in R/R MCL; and an open-label cohort to evaluate first-line Ibr+Ven in treatment-naive (TN) MCL. Primary analysis of the randomized phase showed superior PFS with Ibr+Ven vs Ibr+Pbo in pts with R/R MCL (Wang M et al, Lancet Oncol , in press). Here, we report efficacy and safety of Ibr+Ven in pts with TN MCL in older pts (≥65 y) or younger pts with a TP53 mutation ( TP53 mut) (≥18 y) who are in need of novel and better tolerated treatment options. Methods: Older pts (≥65 y) or pts with a TP53 mut with TN MCL received oral Ibr 560 mg once daily and Ven (5-wk ramp-up to 400 mg once daily) for 2 y, then single-agent Ibr 560 mg until PD or unacceptable toxicity. Primary endpoint was complete response (CR) rate assessed by investigator per Lugano. Key secondary endpoints included overall response rate (ORR), duration of response (DOR), PFS, OS, and time to next treatment. Subgroup analyses were performed according to TP53 mut status and age. Results: In total, 78 TN MCL pts were enrolled. At baseline, 83% of pts were ≥65 y, 97% had ECOG PS of 0–1, 45% had high-risk simplified MIPI score, 31% had bulky disease (≥5 cm), 78% had bone marrow involvement, 46% had splenomegaly, and 37% had TP53 mut. Median time on study was 40.5 mo (range, 0.6+–46.9). CR rate was 69% (95% CI, 58–79), and ORR was 95% (95% CI, 87–99). Median DOR was 37.1 mo (95% CI, 30.3–NE). Median PFS was 40.2 mo, and 3-y OS was 79%. CR rate was 76% in pts ≥65 y without TP53 mut, 44% in pts ≥65 y with TP53 mut, and 73% in pts <65 y with TP53 mut; median PFS was 40.2, 22.0, and 15.4 mo, and 3-y OS was 85%, 66%, and 73%, respectively (Table). Median duration of treatment was 24.0 mo (range, 0.3–46.9). Most common AEs were diarrhea (49%), fatigue (37%), neutropenia (35%), and COVID-19 (32%). Most common grade ≥3 AE was neutropenia (29%). Conclusions: First-line Ibr+Ven showed promising efficacy with high CR rates and durable remissions in pts with TN MCL with and without TP53 mut. Safety was acceptable and trended better in younger pts. Ibr+Ven may be an option for older pts with TN MCL or pts of any age with TP53 mut. Clinical trial information: NCT03112174 . Outcomes (95% CI) Without TP53 mutn=44 With TP53 mut n=29 ≥65 y without TP53 mutn=42 ≥65 y with TP53 mutn=18 <65 y without TP53 mutn=2 <65 y with TP53 mutn=11 TotalN=78 CR rate, % 77(62–89) 55(36–74) 76(61–88) 44(22–69) 100(16–100) 73(39–94) 69(58–79) ORR, % 98(88–100) 90(73–98) 98(87–100) 89(65–99) 100(16–100) 91(59–100) 95(87–99) Median PFS, mo 40.2 (37.2–NE) 22.0(9.2–NE) 40.2(37.2–NE) 22.0(11.3–NE) NR(11.1–NE) 15.4(8.2–NE) 40.2(29.4–NE) 3-y OS, % 86(71–93) 68(47–82) 85(70–93) 66(39–83) 100(100–100) 73(37–90) 79(68–86)
Purpose: To report results of the multicenter, open-label IRAKLIA trial ( NCT05405166 ) of isatuximab subcutaneous (SC) versus intravenous (IV), plus pomalidomide and dexamethasone, in relapsed/refractory multiple myeloma (MM), the first Phase 3 MM trial using an on-body delivery system (OBDS). Methods: Patients with ≥1 prior line of therapy were randomized 1:1 to isatuximab OBDS (1400 mg) or IV (10 mg/kg) weekly in Cycle (C)1, then every 2 weeks, plus pomalidomide (4 mg/day, Day [D]1-21) and dexamethasone (40 mg weekly [age ≥75: 20 mg]) and treated until progression, unacceptable toxicity, or patient request. Co-primary endpoints were overall response rate (ORR; non-inferiority margin, 0.839) and isatuximab C trough (C6D1 predose; non-inferiority margin, 0.8). Non-inferiority of OBDS versus IV was demonstrated if both co-primary endpoints achieved non-inferiority. Results: IRAKLIA randomized 531 patients (OBDS, n=263; IV, n=268). After 12 months median follow-up, ORR was 71.1% (OBDS) and 70.5% (IV; relative risk [95% CI]=1.008 [0.903–1.126]; lower CI exceeded non-inferiority margin). Mean (SD) C6D1 C trough was 499 (259) μg/mL (OBDS) and 340 (169) μg/mL (IV). C trough geometric mean ratio (90% CI) was 1.532 (1.316–1.784); lower CI exceeded non-inferiority margin. Grade ≥3 treatment-emergent adverse event incidences were 81.7% (OBDS) and 76.1% (IV); infusion reaction incidences were 1.5% and 25.0%. Injection site reactions occurred in 0.4% of OBDS injections (all grade 1-2); 99.9% of injections completed without interruption. Conclusion: IRAKLIA demonstrated efficacy and pharmacokinetic non-inferiority between isatuximab OBDS and IV. No unexpected safety signal was observed, with excellent local tolerability of isatuximab OBDS. Efficacy and safety were comparable to isatuximab IV in ICARIA-MM, except the lower OBDS infusion reaction rate. These results support potential use of the OBDS, designed to improve practice efficiency.
Az elhízás napjainkban világszerte súlyos probléma, melynek megoldása multidiszciplináris feladat, amelyben alapvető szerepet játszik a metabolikus sebészet. Hazánkban is néhány munkacsoport egyre magasabb számban végez testsúlycsökkentő műtéteket. Az elvek egységesítése, az országos regiszter kialakítása és az együttműködés kialakítása miatt egy évvel ezelőtt megalakult a Magyar Sebész Társaság Sebészeti Endoszkópos és Robotsebészeti Szekciójának részeként a Metabolikus Sebészeti Munkacsoport. Az ebben részt vevők konszenzusa és az aktuális nemzetközi szakmai ajánlások alapján elkészített és a hazai helyzethez adaptált állásfoglalásban az indikációs elvek, a műtéti típusok, ezek javallatai, eredményei és lehetséges szövődményei, az utógondozás kérdései, valamint a beavatkozások biztonságos végzéséhez szükséges intézményi háttér került megfogalmazásra, illetve közleményünkben ismertetésre.
TP53 aberrations predict chemoresistance and represent a contraindication for the use of standard chemoimmunotherapy in chronic lymphocytic leukaemia (CLL). Recent next-generation sequencing (NGS)-based studies have identified frequent low-burden TP53 mutations with variant allele frequencies below 10%, but the clinical impact of these low-burden TP53 mutations is still a matter of debate. In this study, we aimed to scrutinise the subclonal architecture and clinical impact of TP53 mutations using a sensitive, NGS-based mutation analysis in a 'real-world' cohort of 901 patients with CLL. In total, 225 TP53 mutations were identified in 17.5% (158/901) of the patients; 48% of these alterations represented high-burden mutations, while 52% were low-burden TP53 mutations. Low-burden mutations as sole alterations were identified in 39% (62/158) of all mutated cases with 82% (51/62) of these being represented by a single low-burden TP53 mutation. Patients harbouring low-burden TP53 mutations had significantly lower time to first treatment compared to patients with wild-type TP53. Our study has expanded the knowledge on the frequency, clonal architecture, and clinical impact of low-burden TP53 mutations. By demonstrating that patients with sole low-burden TP53 variants represent more than one-third of patients with TP53 mutations and have an increased risk for treatment initiation, our findings strengthen the need to redefine the threshold of TP53 variant reporting to below 10% in the routine diagnostic setting.
