Riva Carola, Minetto Paola, Chies Maria, Vernarecci Chiara, Colombo Nicoletta, Rosellini Sara, Parodi Alessia, Tedone Elisabetta, Carminati Enrico, Nurra Clara, Puglisi Francesco, Frello Michela, Maio Elena, Ferro Beatrice, Zecchetti Giada, Fugazza Giuseppina, Nozza Paolo, Cea Michele, Lemoli Roberto Massimo, Guolo Fabio
Department of Internal Medicine (DiMI), Clinic of Hematology, University of Genoa, Genoa, Italy.
Dipartimento di Oncologia ed Ematologia (DipOE), IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
Hematol Oncol. 2025 Jan;43(1):e70005. doi: 10.1002/hon.70005.
Secondary acute myeloid leukemia (s-AML) is associated with inferior outcomes with conventional chemotherapy, and fludarabine combinations (FLAG-Ida) have been tested to improve results. More recently, CPX-351 resulted superior to conventional 3 + 7 in s-AML patients. In the UK NCRI AML19 trial, AML patients were randomized to receive either FLAG-Ida or CPX-351. Subgroup analysis revealed better overall survival (OS) with CPX-351 in patients with MDS-related gene mutations. Unfortunately, minimal residual disease (MRD) was evaluated only in a minority of patients. The aim of this study was to further disclose the mechanisms of higher efficacy of CPX-351 in s-AML, with a focus on MRD. We analyzed 183 consecutive s-AML elderly patients (median age 69, range 60-77) treated with CPX-351 (n = 82) or receiving FLAG-Ida (n = 101). Complete remission (CR) rate and MRD negativity probability were higher among patients receiving CPX-351 (MRD negative CR rate of 40/64, 62.5%, compared to 25/55, 45% in patients who received FLAG-Ida, p < 0.05). Extra-hematological toxicity was lower in CPX-351 arm, and 30 days mortality was 3.6% and 8% in patients receiving CPX-351 or FLAG-Ida, respectively. Notably, 21/64 (32.8%) CR patients treated with CPX 351 underwent allogeneic stem cell transplantation (HSCT), compared to 5/55 with FLAG-Ida (9%, p < 0.05). Overall, CPX-351 treatment resulted in higher OS (median OS 17.7 vs. 11.2 months with FLAG-Ida, p < 0.05). The better outcome of CPX-351 compared to FLAG-Ida in our cohort may be explained by a greater probability of MRD negativity, alongside with an improved tolerance, enabling more s-AML patients to undergo HSCT.
继发性急性髓系白血病（s-AML）采用传统化疗时预后较差，已对氟达拉滨联合方案（FLAG-Ida）进行了试验以改善疗效。最近，CPX-351在s-AML患者中显示出优于传统3+7方案的疗效。在英国国家癌症研究所AML19试验中，AML患者被随机分配接受FLAG-Ida或CPX-351治疗。亚组分析显示，CPX-351治疗MDS相关基因突变患者的总生存期（OS）更佳。遗憾的是，仅对少数患者进行了微小残留病（MRD）评估。本研究的目的是进一步揭示CPX-351在s-AML中疗效更高的机制，重点关注MRD。我们分析了183例连续接受CPX-351治疗（n=82）或接受FLAG-Ida治疗（n=101）的s-AML老年患者（中位年龄69岁，范围60-77岁）。接受CPX-351治疗的患者完全缓解（CR）率和MRD阴性概率更高（MRD阴性CR率为40/64，62.5%，而接受FLAG-Ida治疗的患者为25/55，45%，p<0.05）。CPX-351组的血液外毒性较低，接受CPX-351或FLAG-Ida治疗的患者30天死亡率分别为3.6%和8%。值得注意的是，接受CPX-351治疗的64例CR患者中有21例（32.8%）接受了异基因造血干细胞移植（HSCT），而接受FLAG-Ida治疗的55例患者中有5例（9%）接受了HSCT（p<0.05）。总体而言，CPX-351治疗的OS更高（中位OS为17.7个月，而FLAG-Ida为11.2个月，p<0.05）。在我们的队列中，CPX-351比FLAG-Ida预后更好，这可能是因为MRD阴性的概率更高，同时耐受性更好，使得更多s-AML患者能够接受HSCT。
