Lymphoma Unit, Department of Onco-Hematology, IRCCS (Istituto di Ricerca e Cura a Carattere Scientifico) San Raffaele Scientific Institute, Milano, Italy.
Division of Hematology, Ospedali Civili di Brescia, Brescia; Italy.
Blood Adv. 2022 Nov 22;6(22):5811-5820. doi: 10.1182/bloodadvances.2022007475.
Patients with aggressive B-cell lymphoma and MYC rearrangement at fluorescence in situ hybridization exhibit poor outcome after R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). In the last decade, 68 patients with Burkitt lymphoma ([BL] n = 46) or high-grade B-cell lymphoma ([HGBCL] single, double, or triple hit; n = 22) were treated with a dose-dense, short-term therapy termed "CARMEN regimen" at 5 Italian centers. Forty-six (68%) patients were HIV+. CARMEN included a 36-day induction with sequential, single weekly doses of cyclophosphamide, vincristine, rituximab, methotrexate, etoposide, and doxorubicin plus intrathecal chemotherapy, followed by high-dose-cytarabine-based consolidation. Patients who did not achieve complete remission (CR) after induction received BEAM (carmustina, etoposide, cytarabine, melfalan)-conditioned autologous stem cell transplantation (ASCT) after consolidation. Sixty-one (90%) patients completed induction, and 59 (87%) completed consolidation. Seventeen patients received ASCT. Grade 4 hematological toxicity was common but did not cause treatment discontinuation; grade 4 nonhematological toxicity was recorded in 11 (16%) patients, with grade 4 infections in 6 (9%). Six (9%) patients died of toxicity (sepsis in 4, COVID-19, acute respiratory distress syndrome). CR rate after the whole treatment was 73% (95% confidence interval [CI], 55% to 91%) for patients with HGBCL and 78% (95% CI, 66% to 90%) for patients with BL. At a median follow-up of 65 (interquartile range, 40-109) months, 48 patients remain event free, with a 5-year progression-free survival of 63% (95% CI, 58% to 68%) for HGBCL and 72% (95% CI, 71% to 73%) for BL, with a 5-year overall survival (OS) of 63% (95% CI, 58% to 68%) and 76% (95% CI, 75% to 77%), respectively. HIV seropositivity did not have a detrimental effect on outcome. This retrospective study shows that CARMEN is a safe and active regimen both in HIV-negative and -positive patients with MYC-rearranged lymphomas. Encouraging survival figures, attained with a single dose of doxorubicin and cyclophosphamide, deserve further investigation in HGBCL and other aggressive lymphomas.
患者患有侵袭性 B 细胞淋巴瘤和荧光原位杂交的 MYC 重排，在 R-CHOP（利妥昔单抗、环磷酰胺、多柔比星、长春新碱、泼尼松）治疗后预后不良。在过去的十年中，意大利的 5 个中心对 68 例伯基特淋巴瘤 ([BL] n=46) 或高级别 B 细胞淋巴瘤 ([HGBCL] 单、双或三打击；n=22) 患者采用一种称为“CARMEN 方案”的密集短期治疗方案。46 例（68%）患者 HIV 阳性。CARMEN 包括 36 天的诱导治疗，连续使用每周一次的环磷酰胺、长春新碱、利妥昔单抗、甲氨蝶呤、依托泊苷和多柔比星联合鞘内化疗，然后进行高剂量阿糖胞苷巩固治疗。诱导治疗后未达到完全缓解 (CR) 的患者在巩固治疗后接受 BEAM（卡莫司汀、依托泊苷、阿糖胞苷、马法兰）预处理的自体干细胞移植 (ASCT)。61 例（90%）患者完成诱导治疗，59 例（87%）完成巩固治疗。17 例患者接受了 ASCT。常见的是 4 级血液学毒性，但并未导致治疗中断；11 例（16%）患者出现 4 级非血液学毒性，6 例（9%）患者出现 4 级感染。6 例（9%）患者因毒性而死亡（4 例败血症、COVID-19、急性呼吸窘迫综合征）。对于 HGBCL 患者，整个治疗后 CR 率为 73%（95%置信区间 [CI]，55%至 91%），对于 BL 患者为 78%（95% CI，66%至 90%）。在中位随访 65（四分位间距，40-109）个月时，48 例患者无事件，HGBCL 患者的 5 年无进展生存率为 63%（95% CI，58%至 68%），BL 患者为 72%（95% CI，71%至 73%），5 年总生存率（OS）分别为 63%（95% CI，58%至 68%）和 76%（95% CI，75%至 77%）。HIV 血清阳性对结果没有不利影响。这项回顾性研究表明，CARMEN 是一种在 HIV 阴性和阳性的 MYC 重排淋巴瘤患者中均安全且有效的方案。在 HGBCL 和其他侵袭性淋巴瘤中，单次给予多柔比星和环磷酰胺即可获得令人鼓舞的生存数据，值得进一步研究。
