BACKGROUND CAR-T cell therapy is likely to be introduced starting from 2021 in patients with relapsed/refractory myeloma (r/r MM) in Europe. In order to qualify for commercial CAR-T treatment, it is assumed that r/r MM patients will have to be exposed to at least three lines of previous treatments including lenalidomide, bortezomib and anti-CD38 treatment. However, the outcome of this particular subgroup of r/r MM patients is largely unknown whereas this knowledge is crucial to estimate the possible benefit of eventual CAR-T treatment. METHODS In this non-interventional, retrospective single-center study, we analyzed all subsequent r/r MM patients treated between 01/2016 (when anti-CD38 treatment was commercially introduced in Switzerland) and 04/2020 at the University Hospital of Bern. Patients were eligible for the study if they had received at least three lines of treatment including one proteasome inhibitor (PI), one immunomodulatory drug (IMID) and one anti-CD38 antibody, and if they were in need of subsequent treatment and effectively received further lines of treatment. RESULTS Among 56 patients fulfilling the criteria of at least three lines of treatment including PI, IMID and anti-CD38 treatment, only 34 (60%) effectively received subsequent further therapy. This suggests that 40% of r/r MM patients never receive additional treatment after at least three lines of treatment including PI, IMID and anti-CD38 treatment. For patients receiving further treatment, the median number of previous lines of treatment was 4.5 (range 2-12), including autologous stem cell transplantation in 31 (91%) patients. 13 (37%) patients were penta-refractory. The most frequently used treatment options were IMID/dexamethasone treatment in 11 (32%) patients, followed by PI/dexamethasone in 10 (29%) patients. 21 (62%) patients received two or more additional lines of therapy. The median PFS was 6.6 months (range 0-36.6 months), the median TTNT was 7.5 months (range 1.4-24.5 months) and the median OS was 13.5 months, (range 0.1-38 months) for the first subsequent treatment. The overall response rate (ORR) to the first subsequent treatment was 41%, with a median duration of the response of 5 months (range 1-37 months). 12% of the patients achieved VGPR or better, with a median duration of response of 8 months (range 3-37 months). CONCLUSIONS Myeloma patients refractory after at least three lines of anti-CD38/PI/IMID treatment have a poor prognosis with a PFS of 6.6 months and OS of 13.5 months. These data may serve as reference to compare the potential benefit of CAR-T treatment in this group of myeloma patients when available in the near future.

中文翻译：

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符合 CAR-T 细胞治疗条件的骨髓瘤患者在 CAR-T 时代之前的真实世界结果。

背景 CAR-T 细胞疗法很可能从 2021 年开始在欧洲的复发/难治性骨髓瘤 (r/r MM) 患者中引入。为了获得商业 CAR-T 治疗的资格，假设 r/r MM 患者将必须接受至少三种先前的治疗，包括来那度胺、硼替佐米和抗 CD38 治疗。然而，这个特定的 r/r MM 患者亚组的结果在很大程度上是未知的，而这一知识对于估计最终 CAR-T 治疗的可能益处至关重要。方法 在这项非干预性、回顾性单中心研究中，我们分析了 01/2016（抗 CD38 治疗在瑞士商业引入时）至 04/2020 在伯尔尼大学医院接受治疗的所有后续 r/r MM 患者。如果患者接受了至少三线治疗，包括一种蛋白酶体抑制剂（PI）、一种免疫调节药物（IMID）和一种抗CD38抗体，并且需要后续治疗并有效地接受了进一步治疗，则符合研究条件治疗线。结果 56 例患者中，至少满足 PI、IMID 和抗 CD38 治疗三线治疗标准的患者中，只有 34 例（60%）有效地接受了后续的进一步治疗。这表明 40% 的 r/r MM 患者在至少接受过三线治疗（包括 PI、IMID 和抗 CD38 治疗）后从未接受过额外的治疗。对于接受进一步治疗的患者，先前治疗线的中位数为 4.5（范围 2-12），包括 31 名（91%）患者的自体干细胞移植。13 名 (37%) 患者为五类难治性患者。最常用的治疗方案是 IMID/地塞米松治疗 11 名（32%）患者，其次是 PI/地塞米松治疗 10 名（29%）患者。21 名 (62%) 患者接受了两种或两种以上的额外治疗。第一次后续治疗的中位 PFS 为 6.6 个月（范围 0-36.6 个月），中位 TTNT 为 7.5 个月（范围 1.4-24.5 个月），中位 OS 为 13.5 个月（范围 0.1-38 个月）。第一次后续治疗的总缓解率 (ORR) 为 41%，中位缓解持续时间为 5 个月（范围 1-37 个月）。12% 的患者达到 VGPR 或更好，中位缓解持续时间为 8 个月（范围 3-37 个月）。结论 至少三线抗 CD38/PI/IMID 治疗后难治的骨髓瘤患者预后不良，PFS 为 6。6 个月和 13.5 个月的 OS。这些数据可作为参考，以比较近期可用时 CAR-T 治疗在这组骨髓瘤患者中的潜在益处。