Selinexor in patients with relapsed or refractory diffuse large B-cell lymphoma (SADAL): a single-arm, multinational, multicentre, open-label, phase 2 trial

Background: Relapsed or refractory diffuse large B-cell lymphoma (DLBCL) is an aggressive cancer with a median overall survival of less than 6 months. We aimed to assess the response to single-agent selinexor, an oral selective inhibitor of nuclear export, in patients with relapsed or refractory DLBCL who had no therapeutic options of potential clinical benefit. Methods: SADAL was a multicentre, multinational, open-label, phase 2b study done in 59 sites in 19 countries. Patients aged 18 years or older with pathologically confirmed diffuse large B-cell lymphoma, an Eastern Cooperative Oncology Group performance status of 2 or less, who had received two to five lines of previous therapies, and progressed after or were not candidates for autologous stem-cell transplantation were enrolled. Germinal centre B-cell or non-germinal centre B-cell tumour subtype and double or triple expressor status were determined by immunohistochemistry and double or triple hit status was determined by cytogenetics. Patients received 60 mg selinexor orally on days 1 and 3 weekly until disease progression or unacceptable toxicity. The study was initially designed to evaluate both 60 mg and 100 mg twice-weekly doses of selinexor; however, the 100 mg dose was discontinued in the protocol (version 7.0) on March 29, 2017, when an improved therapeutic window was observed at 60 mg. Primary outcome was overall response rate. The primary outcome and safety were assessed in all patients who received 60 mg selinexor under protocol version 6.0, or enrolled under protocol versions 7.0 or higher and received at least one dose of selinexor. This trial is registered at ClinicalTrials.gov, NCT02227251 (active but not enrolling). Findings: Between Oct 21, 2015, and Nov 2, 2019, 267 patients were randomly assigned, with 175 allocated to the 60 mg group and 92 to the discontinued 100 mg group. 48 patients assigned to the 60 mg group were excluded due to enrolment before version 6.0 of the protocol; the remaining 127 patients received selinexor 60 mg and were included in analyses of primary outcome and safety. The overall response rate was 28% (36/127; 95% CI 20·7–37·0); 15 (12%) achieved a complete response and 21 (17%) a partial response. The most common grade 3–4 adverse events were thrombocytopenia (n=58), neutropenia (n=31), anaemia (n=28), fatigue (n=14), hyponatraemia (n=10), and nausea (n=8). The most common serious adverse events were pyrexia (n=9), pneumonia (n=6), and sepsis (n=6). There were no deaths judged as related to treatment with selinexor. Interpretation: Single-drug oral selinexor induced durable responses and had a manageable adverse events profile in patients with relapsed or refractory DLBCL who received at least two lines of previous chemoimmunotherapy. Selinexor could be considered a new oral, non-cytotoxic treatment option in this setting

Settler-Colonialism, Memoricide and Indigenous Toponymic Memory: The Appropriation of Palestinian Place Names by the Israeli State

Cartography, place-naming and state-sponsored explorations were central to the modern European conquest of the earth, empire building and settler-colonisation projects. Scholars often assume that place names provide clues to the historical and cultural heritage of places and regions. This article uses social memory theory to analyse the cultural politics of place-naming in Israel. Drawing on Maurice Halbwachs’ study of the construction of social memory by the Latin Crusaders and Christian medieval pilgrims, the article shows Zionists’ toponymic strategies in Palestine, their superimposition of Biblical and Talmudic toponyms was designed to erase the indigenous Palestinian and Arabo-Islamic heritage of the land. In the pre-Nakba period Zionist toponymic schemes utilised nineteenth century Western explorations of Biblical ‘names’ and ‘places’ and appropriated Palestinian toponyms. Following the ethnic cleansing of Palestine in 1948, the Israeli state, now in control of 78 percent of the land, accelerated its toponymic project and pursued methods whose main features were memoricide and erasure. Continuing into the post-1967 occupation, these colonial methods threaten the destruction of the diverse historical cultural heritage of the land

Prognostic value of end-of-induction PET response after first-line immunochemotherapy for follicular lymphoma (GALLIUM): secondary analysis of a randomised, phase 3 trial

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