Brechbühl Simon, Bacher Ulrike, Jeker Barbara, Pabst Thomas
Department of Medical Oncology, Inselspital, University Hospital Bern; University of Bern; Bern, Switzerland.
Department of Hematology and Central Hematology Laboratory, Inselspital, University Hospital Bern; University of Bern; Bern, Switzerland.
Mediterr J Hematol Infect Dis. 2021 Jan 1;13(1):e2021012. doi: 10.4084/MJHID.2021.012. eCollection 2021.
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.
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.
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).
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.
在欧洲，嵌合抗原受体T细胞（CAR-T）疗法可能从2021年起用于复发/难治性骨髓瘤（r/r MM）患者。为符合CAR-T商业化治疗条件，假定r/r MM患者必须接受至少三线包括来那度胺、硼替佐米和抗CD38治疗的前期治疗。然而，这一特定亚组r/r MM患者的预后情况很大程度上未知，而这一信息对于评估最终CAR-T治疗的潜在益处至关重要。
在这项非干预性、回顾性单中心研究中，我们分析了2016年1月（抗CD38治疗在瑞士商业化推出之时）至2020年4月期间在伯尔尼大学医院接受治疗的所有后续r/r MM患者。若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，且需要后续治疗并实际接受了更多线治疗，则符合研究条件。
在56例符合至少三线包括PI、IMID和抗CD38治疗标准的患者中，仅34例（60%）实际接受了后续进一步治疗。这表明40%的r/r MM患者在接受至少三线包括PI、IMID和抗CD38治疗后从未接受额外治疗。对于接受进一步治疗的患者，前期治疗的中位数为4.5线（范围2 - 12线），其中31例（91%）患者接受了自体干细胞移植。13例（37%）患者为五重难治性。最常用的治疗方案是11例（32%）患者接受IMID/地塞米松治疗，其次是10例（29%）患者接受PI/地塞米松治疗。21例（62%）患者接受了两线或更多线的额外治疗。首次后续治疗的中位无进展生存期（PFS）为6.6个月（范围0 - 36.6个月），中位至下次治疗时间（TTNT）为7.5个月（范围1.4 - 24.5个月），中位总生存期（OS）为13.5个月（范围0.1 - 38个月）。首次后续治疗的总缓解率（ORR）为41%，缓解持续时间中位数为5个月（范围1 - 37个月）。12%的患者达到非常好的部分缓解（VGPR）或更好，缓解持续时间中位数为8个月（范围3 - 37个月）。
至少接受三线抗CD38/PI/IMID治疗后难治的骨髓瘤患者预后较差，PFS为6.6个月，OS为13.5个月。这些数据可作为参考，以便在不久的将来CAR-T治疗应用于这组骨髓瘤患者时比较其潜在益处。
