Live MediSum Demo

A multicenter phase 1 trial tested [177Lu]lutetium-dotatate (200 mCi) combined with oral triapine (administered days 1–14 at dose levels 100–200 mg) in patients with well-differentiated gastroenteropancreatic neuroendocrine tumors. Among 31 treated patients, nine experienced dose-limiting toxicities (including Grade 3 anemia, Grade 4 neutropenia, and one Grade 5 cardiac arrest), leading to a recommended phase 2 triapine dose of 150 mg; Grade ≥3 treatment-related adverse events occurred in 77% (predominantly transient cytopenias), and among 28 evaluable patients the objective response rate was 21.4% with median PFS not reached (median follow-up 23.7 months).

In the phase 1/2 TRANSCEND CLL 004 cohort, 56 patients with relapsed/refractory CLL/SLL received lisocabtagene maraleucel (liso-cel; 50×10^6 or 100×10^6 CAR+ T cells) concurrent with ibrutinib, with median follow-up 24.8 months; at the 100×10^6 dose the CR/CRi rate was 45% and overall response rate 86%, median progression-free survival was 31.4 months, and median duration of response was not reached for CR/CRi. Treatment-emergent grade ≥3 adverse events included neutropenia (52%) and anemia (41%), cytokine release syndrome occurred in 80% (grade 3 in 4%) and neurologic events in 41% (grade 3/4 in 11%), while ibrutinib-related TEAEs were reported in 68%.

Using a syngeneic murine model of ALK+ anaplastic large cell lymphoma (ALCL) and immune-cell depletion experiments, the study found that spontaneous immune surveillance is mediated by CD4+ T cells and NK cells and that immune checkpoint inhibitor (PD-L1) monotherapy induced complete remissions in about 50% of treated mice. Mechanistically, PD-L1 blockade relieved Treg-mediated immunosuppression and increased circulating effector CD8+ T cells to prolong survival, while CD4+ T cells were indispensable for initiating and sustaining immunotherapy responses; non-responding animals showed exhausted CD4+ T cells with a Th22-like transcriptional signature.