Response-guided first-line therapy and treatment of relapse in aggressive lymphoma: 10-year follow-up of the PETAL trial

Ulrich Dührsen , Andreas Bockisch , Bernd Hertenstein , Imke E. Karsten , Frank Kroschinsky , Michael Heuser , Andreas Hochhaus , Heinz-Gert Höffkes , Dirk Behringer , Gabriele Prange-Krex , Mareike Tometten , Martin Grieshammer , Götz U. Grigoleit , Oliver Schmalz , Karin Jordan , Helga Bernhard , Tobias Gaska , Aristoteles Giagounidis , Roland Schroers , Uwe M. Martens , M. Neuhäuser
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Abstract

The PETAL (Positron Emission Tomography–Guided Therapy of Aggressive Non-Hodgkin Lymphomas) trial investigated whether treatment intensification after 2 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP; plus rituximab [R] for CD20+ lymphomas) improved survival in aggressive non-Hodgkin lymphoma. A total of 754 patients (87.5%) had a negative and 108 (12.5%) had a positive interim positron emission tomography (iPET) scan. iPET-positive patients were randomly assigned to receive another 6 (R-)CHOP cycles or 6 blocks of a more intensive protocol. Interim PET-negative patients received another 4 cycles of R-CHOP with or without 2 additional doses of R. After a median follow-up of 4 years, treatment intensification had not improved outcome. These results were confirmed after 10.3 years of follow-up. The present analysis also describes the management of relapse that was part of the study. Among 240 relapsing patients, 94 of 133 autologous transplantation–eligible patients (70.7%) and 16 of 107 ineligible patients (15.0%) received the salvage treatments recommended in the study protocol. Adherence to recommendations had no impact on outcome. Best results were seen after allogeneic transplantation, followed by autologous transplantation and treatment without transplantation (5-year overall survival rate, 64.3% vs 45.5% vs 22.6%), but patients undergoing allogeneic transplantation were significantly younger and their disease was well controlled at the time of transplantation. Early outcome prediction by iPET, alone or in combination with other methods, is a powerful tool to investigate the value of immunological treatment options for patients with a poor response to chemotherapy. This trial was registered at ClinicalTrials.gov as #NCT00554164.

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反应引导的一线疗法和侵袭性淋巴瘤的复发治疗:PETAL 试验的 10 年随访
摘要PETAL(正电子发射断层扫描引导的侵袭性非霍奇金淋巴瘤治疗)试验研究了在环磷酰胺、多柔比星、长春新碱和泼尼松(CHOP;CD20+淋巴瘤加利妥昔单抗[R])治疗2个周期后加强治疗是否能提高侵袭性非霍奇金淋巴瘤患者的生存率。共有 754 名患者(87.5%)的中期正电子发射断层扫描(iPET)结果为阴性,108 名患者(12.5%)的中期正电子发射断层扫描(iPET)结果为阳性。中位随访 4 年后,强化治疗并未改善疗效。这些结果在随访 10.3 年后得到了证实。本分析报告还介绍了作为研究一部分的复发治疗情况。在240名复发患者中,133名符合自体移植条件的患者中有94名(70.7%)和107名不符合条件的患者中有16名(15.0%)接受了研究方案中建议的挽救治疗。遵守建议对结果没有影响。接受同种异体移植的疗效最好,其次是自体移植和不进行移植的治疗(5年总生存率分别为64.3% vs 45.5% vs 22.6%),但接受同种异体移植的患者明显更年轻,而且移植时病情控制良好。通过iPET单独或结合其他方法进行早期结果预测,是研究化疗反应不佳患者免疫治疗方案价值的有力工具。该试验已在 ClinicalTrials.gov 注册,编号为 #NCT00554164。
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