WHO CLASSIFICATION OF TUMOURS OF HAEMATOPOIETIC AND LYMPHOID TISSUES , WHO CLASSIFICATION OF TUMOURS OF HAEMATOPOIETIC AND LYMPHOID TISSUES , کتابخانه مرکزی دانشگاه علوم پزشکی تهران

WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues

Background No effective systemic therapy exists for patients with advanced hepatocellular carcinoma. A preliminary study suggested that sorafenib, an oral multikinase inhibitor of the vascular endothelial growth factor receptor, the platelet-derived growth factor receptor, and Raf may be effective in hepatocellular carcinoma. Methods In this multicenter, phase 3, double-blind, placebo-controlled trial, we randomly assigned 602 patients with advanced hepatocellular carcinoma who had not received previous systemic treatment to receive either sorafenib (at a dose of 400 mg twice daily) or placebo. Primary outcomes were overall survival and the time to symptomatic progression. Secondary outcomes included the time to radiologic progression and safety. Results At the second planned interim analysis, 321 deaths had occurred, and the study was stopped. Median overall survival was 10.7 months in the sorafenib group and 7.9 months in the placebo group (hazard ratio in the sorafenib group, 0.69; 95% confidence interval, 0.55 to 0.87; P<0.001). There was no significant difference between the two groups in the median time to symptomatic progression (4.1 months vs. 4.9 months, respectively, P=0.77). The median time to radiologic progression was 5.5 months in the sorafenib group and 2.8 months in the placebo group (P<0.001). Seven patients in the sorafenib group (2%) and two patients in the placebo group (1%) had a partial response; no patients had a complete response. Diarrhea, weight loss, hand-foot skin reaction, and hypophosphatemia were more frequent in the sorafenib group. Conclusions In patients with advanced hepatocellular carcinoma, median survival and the time to radiologic progression were nearly 3 months longer for patients treated with sorafenib than for those given placebo.

/pdf/sorafenib-in-advanced-hepatocellular-carcinoma-3xdq9sbovw.pdf

Sorafenib in Advanced Hepatocellular Carcinoma

http://aiocm.org/member/Immunity,%20Inflammation,%20and%20Cancer.pdf

Immunity, Inflammation, and Cancer

EASL-EORTC clinical practice guidelines : management of hepatocellular carcinoma

Background The aggressive and heterogeneous nature of lung cancer has thwarted efforts to reduce mortality from this cancer through the use of screening. The advent of low-dose helical computed tomography (CT) altered the landscape of lung-cancer screening, with studies indicating that low-dose CT detects many tumors at early stages. The National Lung Screening Trial (NLST) was conducted to determine whether screening with low-dose CT could reduce mortality from lung cancer. Methods From August 2002 through April 2004, we enrolled 53,454 persons at high risk for lung cancer at 33 U.S. medical centers. Participants were randomly assigned to undergo three annual screenings with either low-dose CT (26,722 participants) or single-view posteroanterior chest radiography (26,732). Data were collected on cases of lung cancer and deaths from lung cancer that occurred through December 31, 2009. Results The rate of adherence to screening was more than 90%. The rate of positive screening tests was 24.2% with low-dose CT and 6.9% with radiography over all three rounds. A total of 96.4% of the positive screening results in the low-dose CT group and 94.5% in the radiography group were false positive results. The incidence of lung cancer was 645 cases per 100,000 person-years (1060 cancers) in the low-dose CT group, as compared with 572 cases per 100,000 person-years (941 cancers) in the radiography group (rate ratio, 1.13; 95% confidence interval [CI], 1.03 to 1.23). There were 247 deaths from lung cancer per 100,000 person-years in the low-dose CT group and 309 deaths per 100,000 person-years in the radiography group, representing a relative reduction in mortality from lung cancer with low-dose CT screening of 20.0% (95% CI, 6.8 to 26.7; P=0.004). The rate of death from any cause was reduced in the low-dose CT group, as compared with the radiography group, by 6.7% (95% CI, 1.2 to 13.6; P=0.02). Conclusions Screening with the use of low-dose CT reduces mortality from lung cancer. (Funded by the National Cancer Institute; National Lung Screening Trial ClinicalTrials.gov number, NCT00047385.).

/pdf/reduced-lung-cancer-mortality-with-low-dose-computed-315bk0rtxu.pdf

Reduced lung-cancer mortality with low-dose computed tomographic screening.

7531 Background: Treatment options are limited for patients (pts) with R/R DLBCL who are not candidates for autologous stem cell transplant (ASCT). ROR1 is an oncofetal protein pathologically expressed in hematologic malignancies including DLBCL. In the phase 1 first-in-human study in hematologic malignancies (waveLINE-001), the ROR1-targeting antibody-drug conjugate zilovertamab vedotin (ZV) showed promising activity and manageable safety in R/R DLBCL. The single-arm, open-label, phase 2 waveLINE-004 study (NCT05144841) is designed to evaluate activity of ZV monotherapy in pts with R/R DLBCL. Early data are reported. Methods: Eligible pts were ≥18 y old, had histologically confirmed DLBCL by WHO classification, measurable disease per Lugano 2014 criteria, PET-positive disease, and ECOG PS of 0-2. Pts must have received ≥2 prior lines of therapy (including an alkylating agent, anthracycline, and an anti-CD20 antibody) with progression after or ineligibility for ASCT and CAR T-cell therapy. All pts received ZV 2.5 mg/kg IV Q3W until disease progression, unacceptable toxicity, or withdrawal. Primary end point was ORR per Lugano 2014 criteria. Safety and tolerability was a secondary end point. Safety was evaluated in all pts who received ≥1 dose of treatment; efficacy was reported for pts with ≥3 mo follow-up. Results: At data cutoff (Nov 16, 2022), 40 pts enrolled and received ≥1 dose of treatment; 23 (58%) had discontinued and 17 (43%) were ongoing. Median age was 68.0 y, 29 (73%) pts were male, 37 (93%) had an ECOG PS of 0 or 1, 24 (60%) had ≥3 prior lines of therapy, and 10 (25%) received prior ASCT. 11 (28%) pts received prior CAR-T. Median follow-up (range) was 2.6 mo (0.3-7.9) for all pts and 6.0 mo (3.0-7.9) for pts in the efficacy analysis (n = 20). ORR by investigator review was 30% (95% CI, 11.9-54.3), with 2 pts having a CR and 4 a PR; 5 pts had SD (DCR, 55% [95% CI, 31.5-76.9]). Treatment related AEs (TRAEs) occurred in 28 (70%) pts, most commonly (≥15%) diarrhea (9 [23%]), anemia (8 [20%]), neutropenia (7 [18%]), neutrophil count decreased (7 [18%]), and alopecia (6 [15%]). Grade 3/4 TRAEs occurred in 16 (40%) pts, most commonly (≥10%) neutropenia (7 [18%]), anemia (6 [15%]), and neutrophil count decreased (4 [10%]). Discontinuation due to a TRAE of diabetic ketoacidosis occurred in 1 (3%) pt. Grade 1/2 treatment-related peripheral neuropathy occurred in 6 (15%) pts; no grade 3/4 AEs occurred. Dose reduction due to treatment-related peripheral neuropathy occurred in 3 (8%) pts. No infusion reaction or tumor lysis syndrome due to treatment occurred and no pts died because of TRAEs. Conclusions: Early results show that ZV had clinically meaningful antitumor activity in pts with R/R DLBCL who progressed after or have been ineligible for ASCT and/or CAR-T. Additionally, the safety profile was manageable and consistent with other monomethyl auristatin E–containing agents. Clinical trial information: NCT05144841 .

Zilovertamab vedotin (MK 2140) in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL): Early results from the phase 2 waveLINE-004 study.

In Response to Dr. Russi and Colleagues

Reply to Y. Pointreau et al

A phase 2 study of zilovertamab vedotin as monotherapy or in combination in patients (pts) with aggressive and indolent B‐cell malignancies: waveLINE‐006

Introduction CAR T-cell therapy has emerged as a promising new immuno-oncology treatment that engages the patient’s immune system to fight certain hematological malignancies, including diffuse large B-cell lymphoma (DLBCL). In the European Union (EU), CAR T-cell therapies have been approved for relapsed/refractory (R/R) DLBCL patients since 2018, but patient access is often still limited or delayed. This paper is aimed at discussing challenges to access and possible solutions in the largest four EU countries. Methods The analysis relied on literature review, market data collection, since homogeneous data coming from registries were not available, and discussion with experts coming from all four countries. Results We calculated that in 2020, between 58% and 83% of R/R DLBCL patients (EMA approved label population) or between 29% and 71% of the estimated medically eligible R/R DLBCL patients, were not treated with a licensed CAR T-cell therapy. Common challenges along the patient journey that may result in limited access or delays to CAR T-cell therapy were identified. These include timely identification and referral of eligible patients, pre-treatment funding approval by authorities and payers, and resource needs at CAR T-cell centers. Discussion These challenges, existing best practices and recommended focus areas for health systems are discussed here, with the aim to inform necessary actions for overcoming patient access challenges for current CAR T-cell therapies as well as for future cell and gene therapies.

https://www.frontiersin.org/articles/10.3389/fmed.2023.1128295/pdf

Armando Santoro

Papers

Zilovertamab vedotin (MK 2140) in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL): Early results from the phase 2 waveLINE-004 study.

In Response to Dr. Russi and Colleagues

Reply to Y. Pointreau et al

A phase 2 study of zilovertamab vedotin as monotherapy or in combination in patients (pts) with aggressive and indolent B‐cell malignancies: waveLINE‐006

Comparative analysis of CAR T-cell therapy access for DLBCL patients: associated challenges and solutions in the four largest EU countries