Understanding and treating myelofibrosis
Nico Gagelmann shared a post on X:
“Understanding and treating myelofibrosis
A short thread on selected clinical abstracts.
Navtemadlin for JAK inhibitor refractory myelofibrosis (BOREAS):
- reduced CD34 + counts by -82 percent at Week 24
- 47 percent of Navtemadlin-treated patients improved fibrosis grade at Week 24
- more than 50 percent reductions in driver mutations in 18 percent
Authors: John O. Mascarenhas, Prithviraj Bose, Hsin-An Hou, Wojciech Homenda, David Ross, Sanjay R Mohan, Jean-Jacques Kiladjian, Haifa Kathrin Al-Ali, Andrew Charles Perkins, Yulia Khalina, Tracy Clevenger, Zhuying Huang, Jesse McGreivy, Wayne Rothbaum, Srdan Verstovsek, Alessandro M. Vannucchi.
- outperformed BAT in low and high baseline platelet groups for SVR35 (low: 47 percent vs 0 percent; high: 35 percent vs 10 percent)
- platelet increases notable early (low: +43 percent vs +11 percent; high: +19 percent vs -4.5 percent)
Authors: Haifa Kathrin Al-Ali, Claire Harrison, Ruben Mesa, Moshe Talpaz, Blanca Xicoy, Francesco Passamonti, Alessandro Vannucchi, Patrick Brown, Christopher Hernandez, Jia Wang, Jun He, Jean-Jacques Kiladjian.
Nuvisertib (TP-3654), a PIM1 kinase inhibitor:
- 31 percent SVR25, and 50 percent TSS50 response
- Significant reductions in bone pain, fatigue, night sweats
- 33 percent improved Hemoglobin ≥1 g/dL; 32 percent platlets recovery in low baseline group
- common Grade 1/2 AEs included nausea and diarrhea
Authors: Firas El Chaer, Lindsay A.M. Rein, Junichiro Yuda, Kazuya Shimoda, Akiyoshi Takami, Michiko Ichii, James McCloskey, Joseph M. Scandura, Alessandra Iurlo, Prithviraj Bose, Tamanna Haque, Alessandro Lucchesi, Shuichi Shirane, Giulia Benevolo, Idoroenyi Amanam, Jean-Jacques Kiladjian, Pankit Vachhani, Srinivas K Tantravahi, Yasushi Onishi, Ciro Rinaldi, Marcello Rotta, Nikki Granacher, Anand Ashwin Patel, Michael Loschi, Samah Alimam, Terrence Bradley, Stanley Cheung, Vincent Ribrag, Sujan Kabir, Karen Ansaldo, Masataka Seki, Vincent Loksa, Zhonggai Li, Jason M. Foulks, Jatin Shah, Raajit Rampal.
TP53 in MPN, context matters:
- Best survival: chronic phase without multihit TP53 or complex karyotype (55 months)
- Intermediate: chronic phase + multihit TP53 or complex karyotype
- Worst: MPN-BP/AP with or without multihit TP53 or complex karyotype (4 months)
TP53 Mutations in Myeloproliferative Neoplasms: Context-Dependent Evaluation of Prognostic Relevance
Authors: Ayalew Tefferi, Maymona Abdelmagid, Giuseppe Gaetano Loscocco, Kebede Begna, Aref Al-Kali, James M. Foran, Jeanne Palmer, Talha Badar, Mrinal M. Patnaik, Kaaren K. Reichard, Rong He, Cinthya Zepeda Mendoza, Mithun V Shah, Attilio Orazi, Daniel A. Arber, Animesh D. Pardanani, Alessandro M. Vannucchi, Devendra Hiwase, Naseema Gangat, Paola Guglielmelli.
Personalized Transplant Decision Making for Myelofibrosis:
- Early HCT (within 1-3 years): for high/intermediate DIPSS, MIPSS70, MYSEC-PM, and TP53
- Delayed HCT: Favored in lower-risk cases or with ASXL1 mutations only in SMF
- response to JAKi influenced timing
Authors: Nico Gagelmann, Barbara Mora, Filippo Branzanti, Alessandro Maria Vannucchi, Massimo Breccia, Giuseppe Alberto Maria Palumbo, Massimiliano Bonifacio, Erika Morsia, Elena Maria Elli, Mario Tiribelli, Giulia Benevolo, Mirko Farina, Fabrizio Pane, Roberto Massimo Lemoli, Giovanni Caocci, Alessia Tieghi, Gianni Binotto, Francesco Cavazzini, Bruno Martino, Alessandro Isidori, Margherita Maffioli, Elisa Rumi, Tiziano Barbui, Francisco Cervantes, Matteo Giovanni Della Porta, Andrew T. Kuykendall, Marianna Caramella, Alessandra Iurlo, Valerio De Stefano, Jean-Jacques Kiladjian, David Ross, Jason Gotlib, Timothy Devos, Marco Ruggeri, Richard T. Silver, Rachel B. Salit, Thomas Schroeder, Carmelo Gurnari, Simona Pagliuca, Christina Rautenberg, Marie Robin, Marie-Thérèse Rubio, Jaroslaw Maciejewski, Alessandro Rambaldi, Maria Chiara Finazzi, Andrea Bacigalupo, Patrizia Chiusolo, Hans Christian Reinhardt, Bart L. Scott, Nicolaus Kröger, Francesco Passamonti, Francesca Palandri.
Pulmonary hypertension in MPN:
- associated with older age, higher VAF, larger spleens, more MF
- more heart failure (15 percent)
- increased hematologic risk and major adverse cardiovascular events
- RV dysfunction (TAPSE) and high cardiac output raised risks
Authors: Orly Leiva, Steven Soo, Nathaniel Smilowitz, Harmony Reynolds, Binita Shah, Samuel Bernard, Michelle Hyunju Lee, Chi-Joan How, Gabriela S. Hobbs.”
Selinexor + Ruxolitinib:
- 40 percent achieved more than 50 percent spleen volume reduction, 87 percent had symptom alleviation, 41 percent had more than 50 percent TSS reduction, 56 percent transfusion-dependent patients became independent
- Common TEAEs included nausea (37 percent), anemia (37 percent), and thrombocytopenia (5 percent).
Authors: Minghui Duan, Lan Ma, Qiuling Wu, PhD, Hong Liang, Wei Wang, Lijun Mu, Hai Lin, Hebing Zhou, Hong-xia Shi, Jinghua Wang, Hongmei Jing.
A Phase Ib study of CXCR4-enriched T-reg cell therapy + Ruxolitinib:
- Symptoms: 38 percent median reduction in TSS, more than 50 percent reduction in 4/9 patients
- 4/6 patients had spleen volume reduction, 1 with more than 35 percent
- Reduced transfusion dependency in two
Authors: Lucia Masarova, Meixian Huang, Swati Goel, Sharon Bledsoe, Naveen Pemmaraju, Tapan M. Kadia, Prithviraj Bose, Jo Ishizawa, Guillermo Montalban-Bravo, Mi-Ae Lyu, Tara Sadeghi, Simrit Parmar, Christopher R. Flowers, Hagop M. Kantarjian.
Nico Gagelmann is a physician and scientist who co-founded and co-chairs the European Society for Blood and Marrow Transplantation (EBMT) Trainee Committee, and he also serves as the chair of the EBMT subcommittee focused on CAR-T cell therapies for plasma cell disorders. His work is particularly impactful in the realm of CAR-T treatments for multiple myeloma, where he has contributed to advancing research and clinical approaches.
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