Saba Ludovic, Nasr Lewis, Manrique-Succar Jorge, Diacovo Julia, Chaulagain Chakra
Department of Hematology and Medical Oncology, Cleveland Clinic Florida, Weston, FL, USA.
The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Ann Transl Med. 2024 Oct 20;12(5):96. doi: 10.21037/atm-23-1945. Epub 2024 Aug 16.
Clonal hematopoiesis of indeterminate potential (CHIP) is characterized by genetic alterations associated with hematologic neoplasms, posing clinical challenges in managing concurrent hematological malignancies. CHIP may complicate the treatment landscape due to its potential to influence disease progression and treatment response. We report a 73-year-old male with multiple myeloma (MM) harboring a CHIP PPM1D mutation, elucidating the complexities and therapeutic considerations in such cases.
After four cycles of cyclophosphamide, bortezomib, and dexamethasone therapy, he achieved a partial response, followed by complete hematologic response (CR) post eight cycles of lenalidomide, dexamethasone, and bortezomib therapy. Despite this, upfront autologous hematopoietic stem cell transplantation (HSCT) was initially deemed unsuitable due to positive PPM1D CHIP status. HSCT proceeded after aggressive relapse with clonal evolution but yielded short-lived response. Following failure of >4 lines of therapy, he received chimeric antigen receptor T (CAR-T) cell therapy (ciltacabtagene autoleucel) for salvage. This approach successfully induced remission, which was maintained for 6 months.
This case report highlights MM management complexities in CHIP presence, suggesting potential utility of HSCT and CAR-T cell therapy. Prospective studies are necessary to evaluate the safety and efficacy of these therapies in myeloma patients with concurrent CHIP, aiming to optimize treatment strategies and improve outcomes in this challenging clinical context.
不确定潜能的克隆性造血（CHIP）的特征是存在与血液系统肿瘤相关的基因改变，这给同时发生的血液系统恶性肿瘤的管理带来了临床挑战。CHIP可能会使治疗情况变得复杂，因为它有可能影响疾病进展和治疗反应。我们报告了一名73岁患有多发性骨髓瘤（MM）且携带CHIP PPM1D突变的男性患者，阐明了此类病例的复杂性和治疗考量。
在接受了四个周期的环磷酰胺、硼替佐米和地塞米松治疗后，他达到了部分缓解，随后在接受了八个周期的来那度胺、地塞米松和硼替佐米治疗后达到了完全血液学缓解（CR）。尽管如此，由于PPM1D CHIP状态为阳性，最初认为前期自体造血干细胞移植（HSCT）不合适。在出现伴有克隆进化的侵袭性复发后进行了HSCT，但缓解期短暂。在超过4线治疗失败后，他接受了嵌合抗原受体T（CAR-T）细胞治疗（西达基奥仑赛）进行挽救。这种方法成功诱导了缓解，并维持了6个月。
本病例报告突出了存在CHIP时MM管理的复杂性，提示了HSCT和CAR-T细胞治疗的潜在效用。有必要进行前瞻性研究，以评估这些疗法在同时患有CHIP的骨髓瘤患者中的安全性和有效性，旨在优化治疗策略并改善这一具有挑战性的临床情况下的治疗结果。
