دورية أكاديمية
Long-lasting response to lorlatinib in patients with ALK-driven relapsed or refractory neuroblastoma monitored with circulating tumor DNA analysis.
| العنوان: | Long-lasting response to lorlatinib in patients with ALK-driven relapsed or refractory neuroblastoma monitored with circulating tumor DNA analysis. |
|---|---|
| المؤلفون: | Ek T; Sahlgrenska University Hospital, Gothenburg, Sweden., Ibrahim RR; Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden., Vogt H; Crown Princess Victoria Children's Hospital, Linköping, Sweden., Georgantzi K; Karolinska University Hospital, Stockholm, Sweden., Träger C; Uppsala University Hospital, Uppsala, Sweden., Gaarder J; Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden., Djos A; Sahlgrenska Academy at University of Gothenburg, Göteborg, Sweden., Rahmqvist I; Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden., Mellström E; Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden., Pujol-Calderón F; Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden., Vannas C; Institute of Biomedicine, Gothenburg University, Gothenburg, Sweden., Hansson L; Sahlgrenska University Hospital, Gothenburg, Sweden., Fagman H; University of Gothenburg, Göteborg, Sweden., Treis D; Karolinska Institutet, Stockholm, Sweden., Fransson S; University of Gothenburg, Gothenburg, Sweden., Österlund T; University of Gothenburg, Gothenburg, Sweden., Chuang TP; University of Gothenburg, Gothenburg, Sweden., Verhoeven BM; Karolinska Institutet, Stockholm, Sweden., Ståhlberg A; Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden., Palmer RH; Institute of Biomedicine, Gothenburg, Sweden., Hallberg B; Institute of Biomedicine, Gothenburg, Sweden., Martinsson T; Sahlgrenska Academy at the University of Gothenburg, Göteborg, Sweden., Kogner P; Karolinska Institutet, Stockholm, Sweden., Dalin M; Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden. |
| المصدر: | Cancer research communications [Cancer Res Commun] 2024 Aug 23. Date of Electronic Publication: 2024 Aug 23. |
| Publication Model: | Ahead of Print |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association for Cancer Research Country of Publication: United States NLM ID: 9918281580506676 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2767-9764 (Electronic) Linking ISSN: 27679764 NLM ISO Abbreviation: Cancer Res Commun Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [Philadelphia, Pennsylvania] : American Association for Cancer Research, [2021]- |
| مستخلص: | Patients with ALK-driven neuroblastoma may respond to tyrosine kinase inhibitors, but resistance to treatment occurs and methods currently used for detection of residual disease have limited sensitivity. Here we present a national unselected cohort of five patients with relapsed or refractory ALK-driven neuroblastoma treated with lorlatinib as monotherapy, and test the potential of targeted circulating tumor DNA (ctDNA) analysis as a guide for treatment decisions in these patients. We developed a sequencing panel for ultrasensitive detection of ALK mutations associated with neuroblastoma or resistance to tyrosine kinase inhibitors and used it for ctDNA analysis in 83 plasma samples collected longitudinally from the four patients who harbored somatic ALK mutations. All four patients with ALK p.R1275Q experienced major responses and were alive 35-61 months after starting lorlatinib. A fifth patient with ALK p.F1174L initially had a partial response but relapsed after 10 months of treatment. In all cases, ctDNA was detected at the start of lorlatinib single agent treatment and declined gradually, correlating with clinical responses. In the two patients exhibiting relapse, ctDNA was increased nine and three months before clinical detection of disease progression, respectively. In one patient harboring HRAS p.Q61L in the relapsed tumor, retrospective ctDNA analysis showed that the mutation appeared de novo after eight months of lorlatinib treatment. We conclude that some patients with relapsed or refractory high-risk neuroblastoma show durable responses to lorlatinib as monotherapy, and targeted ctDNA analysis is effective for evaluation of treatment and early detection of relapse in ALK-driven neuroblastoma. |
| تواريخ الأحداث: | Date Created: 20240823 Latest Revision: 20240823 |
| رمز التحديث: | 20240823 |
| DOI: | 10.1158/2767-9764.CRC-24-0338 |
| PMID: | 39177282 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2767-9764 |
|---|---|
| DOI: | 10.1158/2767-9764.CRC-24-0338 |