Background: 

Immunotherapy may lead to durable remissions in patients with relapsed and refractory acute lymphoblastic leukemia (R/R ALL). Patients receiving immunotherapy with a lower disease burden tend to have improved long-term outcomes and less toxicity. Thus, an induction protocol to achieve lower disease burden is required. Bortezomib added to a 4-drug induction was shown to lead to high rates of remission in R/R ALL patients. Inclusion of anthracyclines in this protocol may preclude most patients, having maximized the cumulative dose of anthracyclines. Thus, our goal was to evaluate anthracycline-free bortezomib-based induction for patients with R/R ALL.

Procedure: 

We conducted a retrospective analysis of patients treated with bortezomib-based protocols for R/R ALL between 2011 and 2019 at our center. Data regarding toxicity and response rate was collected and analyzed.

Results: 

Eighteen children with R/R ALL were treated with bortezomib-based induction, 13 of them without anthracyclines. Eleven patients did not complete the induction course: 6 due to toxicity, and 5 due to physician decision to proceed to immunotherapy early. Two events of treatment-related mortality occurred. There was no significant difference in toxicity between patients who treated with anthracycline and those who were not. Ten patients achieved complete remission, with 4 patients having polymerase-chain-reaction minimal residual disease below 10⁻⁴. Fifteen patients proceeded directly to immunotherapy: 11 patients received CD19 chimeric-antigen receptor-T-cells, 2 blinatumomab and 2 hematopoietic stem cell transplant.

Conclusion: 

Anthracyclines can be safely omitted from bortezomib-based therapies in patients with R/R ALL, when planning to proceed to immunotherapy.

中文翻译：

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基于硼替佐米的无蒽环类药物诱导小儿复发性 ALL 作为免疫治疗的桥梁

背景： 

免疫疗法可能会导致复发和难治性急性淋巴细胞白血病 (R/R ALL) 患者的持久缓解。接受具有较低疾病负担的免疫治疗的患者往往具有改善的长期结果和较少的毒性。因此，需要一种诱导方案来降低疾病负担。硼替佐米添加到 4 种药物诱导中被证明可导致 R/R ALL 患者的高缓解率。在本方案中纳入蒽环类药物可能会排除大多数患者，因为已最大限度地增加了蒽环类药物的累积剂量。因此，我们的目标是评估R/R ALL 患者基于无蒽环类药物的硼替佐米诱导。

程序： 

我们对 2011 年至 2019 年间在我们中心接受基于硼替佐米的 R/R ALL 方案治疗的患者进行了回顾性分析。收集和分析有关毒性和反应率的数据。

结果： 

18 名 R/R ALL 儿童接受了基于硼替佐米的诱导治疗，其中 13 名未使用蒽环类药物。11 名患者未完成诱导过程：6 名是由于毒性，5 名是由于医生决定提前进行免疫治疗。发生了两起与治疗相关的死亡事件。接受蒽环类药物治疗的患者与未接受治疗的患者在毒性方面没有显着差异。10 名患者达到完全缓解，其中 4 名患者的聚合酶链反应最小残留病灶低于 10 ^-4。15 名患者直接进行免疫治疗：11 名患者接受 CD19 嵌合抗原受体 T 细胞、2 名博纳吐单抗和 2 名造血干细胞移植。

结论： 

R/R ALL 患者在计划进行免疫治疗时，可以安全地从基于硼替佐米的治疗中省略蒽环类药物。