PECAM is an effective and safe anthracycline-containing regimen for patients with relapsed or refractory non-Hodgkin lymphoma.
PECAM is an effective and safe anthracycline-containing regimen for patients with relapsed or refractory non-Hodgkin lymphoma.
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PECAM 是一种有效且安全的含蒽环类药物治疗方案，适用于复发或难治性非霍奇金淋巴瘤患者。
DOI：
10.1080/10428194.2020.1817442
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Mitani K.
中科院分区：
文献类型：
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作者：
Nakamura F;Arai H;Tokita K;Furuichi S;Sugita-Nagasawa F;Takahashi W;Handa T;Iso H;Tadokoro J;Tsurumi S;Nakamura Y;Nakamura Y;Sasaki K;Seo S;Ichikawa M;Mitani K.
尽管以前未经治疗的弥漫性大B细胞淋巴瘤(DLBCL)的治疗取得了进展[1，2]，但24%的患者在完全缓解(CR)后10年内复发[2]，约10%的患者患有原发难治性疾病[3]。针对复发或难治性侵袭性淋巴瘤的患者已开发出挽救方案[4-7]。一般来说，挽救化疗的总有效率(ORR)为49-74%，但很难获得持久的CR。接受抢救治疗和自体干细胞移植的患者的三年无事件或无进展生存率(PFS)为17-21%[7，8]。接受二线治疗的移植不合格患者的预后很差；他们很少有较长的PFS，他们的中位总生存期(OS)为4.4个月[9]。仍然需要一种能够导致持久缓解的挽救方案。出于对心脏毒性的担忧，二线方案中使用蒽环类药物的做法并未被广泛接受。然而，EPOCH是一种含有阿霉素的抢救方案，非常有效，没有明显的心脏毒性[5]。在这项研究中，我们提出了另一种由强的松龙、依托泊苷、卡铂、阿糖胞苷和米托蒽醌(PECAM)组成的含蒽环类药物的挽救方案，用于对含非蒽环类药物的二线方案无效的复发或难治性淋巴瘤患者。我们回顾分析了PECAM是否有效且不会增加心脏毒性的风险。我们回顾了2010年9月至2020年3月期间，不符合移植条件的复发或难治性DLBCL患者接受至少一个周期的PECAM作为三线方案治疗的情况。中位随访期为5.7个月(1.1~74.2个月)。所有患者均接受CHOP类方案(CHOP[1]或THPCOP[10])，其中利妥昔单抗为一线治疗方案，含非蒽环类药物的抢救方案(DEVIC[11])为二线治疗方案。国际预后指数(IPI)[12]在PECAM开始时确定。这项回溯性研究得到了独居医科大学机构审查委员会的批准。卡铂75 mg/m2/d，静脉滴注2 h；依托泊苷75 mg/m2/d，静脉滴注3 h。第1~4天口服强的松龙20 mg/m2，每日1次，第1~4天口服米托蒽醌8 mg/m2，最多14 mg，第1天静脉滴注1小时，根据年龄和并发症将剂量降至50~80%。对于70岁以上的患者，剂量减少到70%。患者在第0天接受利妥昔单抗(375 mg/m2)治疗。患者每4周治疗一次，最多3个周期。主要终点是总有效率(ORR)，包括最后一个周期PECAM后的完全缓解(CR)和部分缓解(PR)。反应通过计算机断层扫描(CT)进行评估，并根据修订的国际工作组标准进行分类[13]。次要终点为OS、PFS和SAFE。PFS是从第一个PECAM周期开始到复发、进展或因任何原因死亡的日期计算的。OS被定义为从第一个PECAM周期开始到最后一次随访或死于任何原因的时间。OS和PFS按Kaplan-Meier分析进行分析，曲线比较采用Logrank分析。用FISHERLS精确检验比较ORR。所有统计分析均使用EZR版本1.37[14]进行。所有不良反应均为…
Despite the progress in the treatment of previously untreated patients with diffuse large B-cell lymphoma (DLBCL)[1, 2], 24% of patients relapse within 10years of achieving complete response (CR)[2] and approximately 10% of the patients have primary refractory disease [3]. Salvage regimens have been developed for patients with relapsed or refractory aggressive lymphomas [4-7]. In general, the overall response rate (ORR) to salvage chemotherapy is 49-74%, but durable CR is difficult to achieve. The three-year event-free or progression-free survival (PFS) rate is 17-21% for patients who received salvage treatment followed by autologous stem cell transplant [7, 8]. The prognosis of transplant-ineligible patients who received second-line treatment is dismal; they rarely have a long PFS and their median overall survival (OS) was 4.4 months [9]. There remains a need for a salvage regimen that can induce durable remission. The use of anthracycline drugs in second-line regimens is not widely accepted because of concerns about cardiotoxicity. However, EPOCH, a doxorubicin-containing salvage regimen, is highly effective with no significant cardiac toxicity [5]. In this study, we propose another anthracycline-containing salvage regimen consisting of prednisolone, etoposide, carboplatin, cytarabine and mitoxantrone (PECAM) for patients with relapsed or refractory lymphomas who failed to respond to nonanthracycline-containing second-line regimens. We retrospectively analyzed whether PECAM would be effective and not increase the risk of cardiotoxicity. We retrospectively reviewed transplant-ineligible patients with relapsed or refractory DLBCL treated with at least one cycle of PECAM as a third-line regimen between September 2010 and March 2020. The median follow-up was 5.7 months (range, 1.1-74.2 months). All patients received a CHOP-like regimen (CHOP [1] or THPCOP [10]) with rituximab as first-line therapy and a nonanthracycline containing salvage regimen (DeVIC [11]) as second-line therapy. International Prognostic Index (IPI)[12] was determined at the initiation of PECAM. This retrospective study was approved by the Dokkyo Medical University Institutional Review Board. From day 1 to day 4, patients were given 75mg/m2/day of carboplatin (given at 2h intravenously) and 75 mg/m2/day of etoposide (given at 3h intravenously). Cytarabine (total 800mg/m2) was administered by a 96-hour continuous infusion from day 1 to day 4. Prednisolone (20mg/m2/day) was orally administered once daily from day 1 to day 4. Mitoxantrone (8mg/m2, up to 14mg) was given as a one-hour infusion on day 1. The dose was reduced to 50-80% based on age and complications. For patients aged over 70, the dose was reduced to 70%. Patients received rituximab (375mg/m2) on day 0. Patients were treated every four weeks for a maximum of three cycles.The primary end point was overall response rate (ORR), including CR and partial response (PR) after the last cycle of PECAM. Response was assessed by a computed tomography (CT) scan and classified according to the revised International Working Group criteria [13]. The secondary end points were OS, PFS and safety. PFS was calculated from the beginning of the first PECAM cycle until the date of relapse, progression, or death from any cause. OS was defined as the time from the beginning of the first PECAM cycle to the last follow-up or death from any cause. OS and PFS were analyzed according to the Kaplan-Meier analysis, with curve comparisons using logrank analysis. The ORR was compared using FisherLs exact test. All statistical analyses were performed using EZR version 1.37 [14]. All adverse …