ALK positive

P2, N=33, Active, not recruiting, Fundación GECP | Trial primary completion date: Nov 2025 --> Nov 2026

P3, N=71, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not recruiting

Limited CIR beyond 12 months existed for brigatinib and ensartinib. Results from the Asian group's CIR aligned with global trials. Due to lower BM CIR, lorlatinib showed higher BM management cost savings compared to crizotinib and alectinib in Chinese 1 L patients.

Conditioning was based on total body irradiation (TBI) in 30 patients and on chemotherapy in 27 patients, mainly with reduced-toxicity conditioning (RTC; Treosulfan, Fludarabine, and Thiotepa). Our data support the use of TBI-free conditioning and suggest improved outcomes with unrelated donors receiving ATLG prophylaxis. NCT00317408.

Several clinical factors associated with survival were identified. Larger studies are needed to investigate how treatment sequences may be optimized to further improve survival outcomes.

These discrepancies likely reflect biases in model training data and the probabilistic nature of generative language models. Despite this quantified generative bias, the utility of these cohorts for non-epidemiological tasks like educational simulation is discussed, provided methodological transparency is maintained.

The patient was treated with a modified MARIETTA protocol (without rituximab) and consolidated with a carmustine-based autologous stem cell transplant. shows complete metabolic response on PET-CT and MRI brain. This case presents the first successful treatment of a synchronous presentation of CNS and systemic ALK-positive ALCL, and the importance of a multidisciplinary approach for diagnosis.

P=N/A, N=200, Not yet recruiting, Shandong First Medical University and Shandong Academy of Medical Sciences (Shandong Cancer Hospital ＆Institute); Shandong First Medical University

P4, N=178, Not yet recruiting, Beijing chest hospital capital medical university; Beijing Chest Hospital Capital Medical University

P2, N=61, Not yet recruiting, Shenshan Medical Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University; Shenshan Medical Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen Un

From first-generation Crizotinib to third-generation Lorlatinib, successive agents have been refined for target selectivity, central nervous system penetration, and coverage of resistance-associated mutations, substantially improving patient survival and intracranial disease control. Nonetheless, the emergence of acquired resistance remains an overarching challenge, mediated by secondary kinase domain mutations, activation of bypass signaling pathways, and tumor phenotypic transformation. This review presents an integrative synthesis of ALK-targeted therapeutic developments, elucidates underlying resistance mechanisms, and surveys emerging strategies, providing a comprehensive perspective on current advances and future directions in precision management of ALK-driven malignancies.

Their diagnosis requires careful consideration to accurately distinguish rare indolent entities, recently defined large B‑cell lymphomas, and reactive mimics. Recent classifications, including the newly introduced WHO Classification of Pediatric Tumors, increasingly reflect these unique aspects.