Gerds Aaron, Su Derrick, Martynova Anastasia, Pannell Benjamin, Mukherjee Sudipto, O'Neill Caitlin, Sekeres Mikkael, O'Connell Casey
Hematologic Oncology and Blood Disorders, Cleveland Clinic, Cleveland, OH.
Jane Anne Nohl Division of Hematology, Department of Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA.
Clin Lymphoma Myeloma Leuk. 2018 Nov;18(11):e463-e468. doi: 10.1016/j.clml.2018.06.025. Epub 2018 Jun 28.
Myelofibrosis (MF) is one of the classic myeloproliferative neoplasms and can occur de novo or following transformation from polycythemia vera (PPV MF) or essential thrombocythemia (PET MF). It can be associated with constitutional symptoms and splenomegaly, both of which can negatively impact quality of life. The only curative option for MF is allogeneic stem cell transplantation. Studies have shown that JAK2 inhibitors such as ruxolitinib are effective in reducing both splenomegaly and symptom burden. Although there is no approved treatment for patients who progress on ruxolitinib, anecdotal evidence suggests patients may respond to a re-challenge of ruxolitinib after drug cessation.
We conducted a multi-institutional, retrospective case series to study patients who were re-challenged with ruxolitinib after inadequate response to or loss of response with an initial treatment course. Thirteen patients were identified. Six patients had primary MF, 3 patients had PPV MF, and 4 patients had PET MF. Ten patients were JAK2-positive, 2 were CALR-positive, and 1 patient had neither mutation. Nine patients received 1 ruxolitinib re-challenge, and 4 received 2 re-challenges. Response was defined as improvement in constitutional symptoms and/or reduction in spleen size.
During the primary treatment course with ruxolitinib, there was improvement in constitutional symptoms and reduction in spleen size in 92% and 85% of patients, respectively. Following cessation of ruxolitinib, all patients received a first re-challenge course with improvement in symptoms and splenomegaly in 92% and 69%, respectively. Of the 4 patients who received a second re-challenge course of ruxolitinib, all had improvements in spleen size and constitutional symptoms. Six patients have continued on a first or second ruxolitinib re-challenge course with good response.
Our study demonstrates that re-exposure to ruxolitinib following a period of treatment cessation in patients with MF can lead to durable responses with regards to both splenomegaly and symptom burden.
骨髓纤维化（MF）是经典的骨髓增殖性肿瘤之一，可原发发生，也可由真性红细胞增多症（PPV MF）或原发性血小板增多症（PET MF）转化而来。它可伴有全身症状和脾肿大，这两者都会对生活质量产生负面影响。MF的唯一治愈选择是异基因干细胞移植。研究表明，鲁索替尼等JAK2抑制剂可有效减轻脾肿大和症状负担。虽然对于在鲁索替尼治疗中病情进展的患者尚无获批的治疗方法，但轶事证据表明，患者在停药后再次使用鲁索替尼可能有反应。
我们进行了一项多机构回顾性病例系列研究，以研究那些在初始治疗疗程反应不佳或失去反应后再次接受鲁索替尼治疗的患者。共确定了13例患者。6例为原发性MF，3例为PPV MF，4例为PET MF。10例患者JAK2阳性，2例CALR阳性，1例患者无突变。9例患者接受了1次鲁索替尼再治疗，4例接受了2次再治疗。反应定义为全身症状改善和/或脾脏大小缩小。
在鲁索替尼初始治疗疗程中，分别有92%和85%的患者全身症状改善和脾脏大小缩小。鲁索替尼停药后，所有患者均接受了首次再治疗疗程，症状改善和脾肿大缩小的患者分别为92%和69%。在接受鲁索替尼第二次再治疗疗程的4例患者中，所有患者的脾脏大小和全身症状均有改善。6例患者继续接受首次或第二次鲁索替尼再治疗疗程，反应良好。
我们的研究表明，MF患者在停药一段时间后再次使用鲁索替尼，可在脾肿大和症状负担方面产生持久反应。
