Crisà Elena, Mora Elvira, Germing Ulrich, Bally Cecile, Diez Campelo Maria, Myllymäki Mikko, Jädersten Martin, Komrokji Rami, Platzbecker Uwe, Haase Detlef, Hofmann Wolf-Karsten, Al Ali Najla H, Barraco Daniela, Bargay Juan José, Bernal Teresa, López Cadenas Felix, Calvisi Anna, Capodanno Isabella, Cerrano Marco, Ciancia Rosanna, Crugnola Monica, Kündgen Andrea, Finelli Carlo, Fozza Claudio, Frairia Chiara, Freja Ebeling, Ganster Christina, Kubasch Anne Sophie, Jimenez Maria Jose, Latagliata Roberto, Hernandez Mohedo Francisca, Molero Antonieta, Vara Pampliega Miriam, Perez Clara Aparicio, Pietrantuono Giuseppe, Poloni Antonella, Pomares Helena, Recasens Valle, Rüfer Axel, Signori Alessio, Hellstrom-Lindberg Eva, Fenaux Pierre, Sanz Guillermo, Santini Valeria
Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy.
Fondazione Sindromi Mielodisplastiche FISiM-ETS, Bologna, Italy.
Leukemia. 2024 Oct;38(10):2259-2265. doi: 10.1038/s41375-024-02360-1. Epub 2024 Aug 5.
Lenalidomide (LEN) can induce red blood cell-transfusion independence (RBC-TI) in 60-70% of del(5q) myelodysplastic neoplasm (MDS) patients. Current recommendation is to continue LEN in responding patients until failure or progression, with likelihood of toxicity and a high cost for healthcare systems. This HARMONY Alliance study investigated the outcome of MDS del(5q) patients who discontinued LEN while RBC-transfusion independent. We enrolled 118 patients with IPSS-R low-intermediate risk. Seventy patients (59%) discontinued LEN for intolerance, 38 (32%) per their physician decision, nine (8%) per their own decision and one (1%) for unknown reasons. After a median follow-up of 49 months from discontinuation, 50/118 patients lost RBC-TI and 22/30 who underwent cytogenetic re-evaluation lost complete cytogenetic response. The median RBC-TI duration was 56 months. In multivariate analysis, RBC-TI duration after LEN discontinuation correlated with low transfusion burden before LEN therapy, treatment ≥ 12 LEN cycles, younger age and higher Hb level at LEN withdrawal. Forty-eight patients were re-treated with LEN for loss of response and 28 achieved again RBC-TI. These data show that stopping LEN therapy in MDS del(5q) patients who reached RBC-TI allows prolonged maintenance of TI in a large subset of patients.
来那度胺（LEN）可使60%-70%的5号染色体长臂缺失（del(5q)）的骨髓增生异常综合征（MDS）患者实现红细胞输注独立（RBC-TI）。目前的建议是，持续对有反应的患者使用LEN，直至出现失败或进展，这存在毒性风险且对医疗系统成本高昂。这项HARMONY联盟研究调查了已实现RBC-TI但停用LEN的MDS del(5q)患者的预后情况。我们纳入了118例国际预后评分系统修订版（IPSS-R）低-中危患者。70例患者（59%）因不耐受停用LEN，38例（32%）由医生决定停药，9例（8%）自行决定停药，1例（1%）原因不明。在停药后中位随访49个月时，118例患者中有50例失去RBC-TI，30例接受细胞遗传学重新评估的患者中有22例失去完全细胞遗传学缓解。RBC-TI的中位持续时间为56个月。多因素分析显示，LEN停药后RBC-TI持续时间与LEN治疗前输血负担低、治疗≥12个LEN周期、年龄较轻以及LEN停药时血红蛋白水平较高相关。48例患者因反应丧失接受LEN再次治疗，其中28例再次实现RBC-TI。这些数据表明，对于已实现RBC-TI的MDS del(5q)患者停用LEN治疗，可使很大一部分患者长期维持输血独立状态。
