Allogeneic hematopoietic stem cell transplantation (HCT), defined by its underlying graft-versus-multiple myeloma (MM) effect, is a potentially curative approach for high-risk pts. However, relapse remains the main cause of treatment failure. Predictors for post-relapse survival after HCT are not well characterized, and we hypothesized that the time to relapse and the patterns of relapse are prognostic for post-relapse survival.

Methods: All pts with MM who underwent a CD34+-selected alloHCT at Memorial Sloan Kettering Cancer Center on protocol (NCT 01131169/01119066) or off study from 01/2010 to 12/2017 and progressed after alloHCT were included. Pts were conditioned with busulfan (0.8 mg/kg x 10), melphalan (70 mg/m2 × 2), and fludarabine (25mg/m2 × 5). The K-M method was used to estimate OS post-HCT relapse. Significant predictors were considered in a Cox model.

Results: Of the 115 transplanted pts, 60 (52%) relapsed and were analyzed. The median age was 56 yrs (35- 66), 62% male and 82% with high-risk cytogenetics (CG). KPS was ≥ 80 in 100% and ≥ 90 in 52%. Pts received a median of 4 lines of therapy pre-HCT (1-10), with 88% achieving at least a partial response (PR) prior to alloHCT. All pts had received at least one autoHCT. Of the 38% who received a planned or preemptive post-HCT therapy, 13 received DLI and 10 other strategies. Relapse was characterized as very early (<6 mo, 28%), early (6-24 mo, 50%), or late (>24 mo, 22%). At relapse, 27% presented with extramedullary disease (EMD). Median post-relapse OS was significantly different for pts who relapsed very early, early, or late; 4 mo, 17 mo, and 72 mo, respectively (p = 0.002). Age ≥55, relapse with EMD, lower KPS, <PR prior to HCT, <PR by day 100, and no maintenance were also prognostic for worse post-relapse OS in univariate analysis. There was no significant difference for post-relapse OS for number of lines, high-risk CG, or era of alloHCT. In multivariate analysis adjusting for sex and age, risk factors for worse post-relapse OS included very early (HR 4.4, 95%CI 1.4-13.5) or early relapse (HR 2.5, 95%CI 1.4-13.5), relapse with EMD (HR 5.2, 95%CI 2.1-12.9), and lack of DLI as planned post-HCT therapy (HR for DLI compared with no DLI = 0.11, 95%CI 0.01-0.9).

Conclusion: For this very high-risk group of MM pts, differences in time to relapse after alloHCT define very distinct post-relapse survival patterns. Very early relapses were associated with greater chemoresistance and dismal prognosis. In contrast, the median post-relapse OS for late relapses was 6 yrs, suggesting different underlying disease biology and/or host/donor characteristics. Similar to the post-auto setting, relapse with EMD conferred poor prognosis. Of note, post-relapse OS was superior for pts who received a DLI as planned post-HCT therapy prior to relapse. Efforts to characterize optimal post-relapse therapeutic strategies and mechanism(s) driving relapses are ongoing.

异基因造血干细胞移植（HCT）是由其潜在的移植物抗多发性骨髓瘤（MM）效应定义的，是治疗高危患者的潜在方法。但是，复发仍然是治疗失败的主要原因。HCT后复发后存活的预测因素尚不明确，我们假设复发时间和复发方式可预测复发后存活。

方法：纳入所有在协议纪念日（NCT 01131169/01119066）或从01/2010至12/2017接受研究且在alloHCT之后进展的，在Memorial Sloan Kettering癌症中心接受CD34 +选择的alloHCT的MM患者。用白消安（0.8 mg / kg x 10），美法仑（70 mg / m2×2）和氟达拉滨（25mg / m2×5）调节Pts。KM方法用于估计HCT后OS的复发。在Cox模型中考虑了重要的预测因素。

结果：在115例移植的患者中，有60例（52％）复发并进行了分析。中位年龄为56岁（35-66岁），男性为62％，患有高危细胞遗传学（CG）的为82％。KPS在100％中≥80，在52％中≥90。Pts在HCT之前接受了4线治疗的中位数（1-10），其中88％的人在alloHCT之前达到了至少部分反应（PR）。所有患者均接受了至少一项autoHCT。在接受计划或先发性HCT治疗后的38％的人中，有13人接受了DLI和其他10种策略。复发的特征是非常早（<6 mo，28％），早期（6-24 mo，50％）或晚期（> 24 mo，22％​​）。在复发时，27％的患者患有髓外疾病（EMD）。对于非常早，早或晚复发的患者，复发后中位操作系统的中位数差异显着。4 mo，17 mo和72 mo（p = 0.002）。年龄≥55岁，EMD复发，KPS降低，<HCT之前的PR，< 在单变量分析中，到第100天时PR且没有维护也预示了复发后OS恶化的预后。对于行数，高危CG或alloHCT时代，复发后OS没有显着差异。在根据性别和年龄进行调整的多因素分析中，复发后OS恶化的危险因素包括很早（HR 4.4，95％CI 1.4-13.5）或早期复发（HR 2.5，95％CI 1.4-13.5），EMD复发（ HR 5.2，95％CI 2.1-12.9），以及按计划进行的HCT治疗后缺乏DLI（DLI的HR与无DLI的患者相比为0.11，95％CI 0.01-0.9）。

结论：对于这一极高风险的MM pts组，alloHCT后复发时间的差异定义了非常不同的复发后生存模式。早期复发与较高的化学耐药性和不良预后相关。相反，晚期复发的中位复发后OS为6年，表明潜在的疾病生物学和/或宿主/供体特征不同。与自动后设置类似，EMD复发会导致不良预后。值得注意的是，对于计划在复发前接受HLI治疗后接受DLI的患者，复发后OS更为优越。表征最佳复发后治疗策略和驱动复发的机制的研究正在进行中。