CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Functionally high-risk disease is associated with poor outcomes after late-line CAR T-cell therapy for multiple myeloma.
Functionally high-risk disease is associated with poor outcomes after late-line CAR T-cell therapy for multiple myeloma.
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尽管CAR-T 在功能高危多发性骨髓瘤(FHRMM)的早期治疗线中已显示出优越疗效[1, 2],但其在后期治疗线(3+)中用于FHR疾病的结局仍不清楚。
我们描述了单中心FHRMM患者(pts)接受CAR-T 细胞治疗的经验,FHRMM定义为一线治疗后24个月内出现疾病进展(POD)的患者。在208例接受CAR-T 治疗的患者中,117例(56%)患有FHR疾病,既往接受过中位5线治疗(LOT)。FHR患者的髓外疾病(EMD)发生率和移植后12个月内进展率更高。FHR组和非FHR组的中位PFS分别为11个月和13个月(p = 0.15),中位OS分别为34个月和55个月(p = 0.025)。在多变量分析中,EMD和高疾病负荷与较差的OS相关。接受CAR-T 作为晚期LOT的FHRMM患者相比非FHR疾病患者生存结局更差,突显了一线治疗后24个月内POD的不良预后影响。这种关联主要由CAR-T 时活动性EMD和高疾病负荷驱动,强调了将CAR-T 用作FHRMM早期LOT的潜在获益。
While CAR T has shown superior efficacy in earlier line of therapy [1, 2] for functionally high-risk multiple myeloma (FHRMM), outcomes with its use in later lines (3+) for FHR disease remain unknown.
We describe a single-center experience of FHRMM patients (pts), defined as those with progression of disease (POD) < 24 months of frontline therapy, receiving CAR T-cell therapy. Of the 208 pts treated with CAR T, 117 (56%) had FHR disease and had received median of 5 prior lines of therapy (LOT). FHR pts had higher rates of extramedullary disease (EMD) and progression within 12 months of transplant. Median PFS were 11 and 13 months (p = 0. 15), and median OS were 34 and 55 months (p = 0.
025) in the FHR and non-FHR groups, respectively. On multivariable analyses, EMD and high disease burden were associated with inferior OS. FHRMM pts receiving CAR T as late LOT had inferior survival outcomes compared to those with non-FHR disease, underscoring the poor prognostic impact of POD < 24 months from frontline therapy. This association was largely driven by active EMD and high disease burden at the time of CAR T, highlighting the potential benefit of utilizing CAR T as an early LOT for FHRMM.
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