PEMBROLIZUMAB AND RADIATION THERAPY ALONE AS AN ALTERNATIVE TO TRANSPLANT FOR LOCALIZED FAILURE AFTER CHEMOTHERAPY IN HODGKIN LYMPHOMA: A MULTICENTER PHASE II STUDY

IF 3.3 4区医学 Q2 HEMATOLOGY

Hematological Oncology Pub Date : 2025-06-16 DOI:10.1002/hon.70093_129

A. D. Dreyfuss, N. Ganesan, B. S. Imber, M. LaRiviere, D. Isrow, J. Plastaras, J. Svoboda, J. Yahalom, C. H. Moskowitz, A. Moskowitz

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引用次数: 0

Abstract

Background: Chemotherapy (chemo) followed by stem cell transplant (SCT) is standard of care for relapsed/refractory (RR) Hodgkin Lymphoma (HL). In a phase II study, we evaluated pembrolizumab (pembro) with involved site radiation therapy (ISRT) as an alternative salvage approach for localized favorable relapse.

Methods: Patients with RR stage IA/IIA, non-bulky (< 10cm) HL after one line of therapy had a PETCT simulation followed by pembro 200 mg IV q 21d for 4 cycles and PETCT simulation 3 wks later. Patients then received ISRT per response as follows: (1) 20 Gy for complete metabolic response (CMR) defined by Deauville Score (DS) 1–3; (2) 30 Gy for partial metabolic response (PMR) or stable disease (SD) (DS 4–5) and negative biopsy; or (3) 36–40 Gy for PMR/SD and positive biopsy. Patients who progressed (PD) were taken off study. PETCT response was documented 4–6 weeks after ISRT. The primary endpoint was CMR rate after pembro-RT. Secondary endpoints were response to single agent pembro, 2-year progression free survival (PFS), and toxicity.

Results: 22 of planned 22 patients enrolled with median age of 36 (range 22–66) and 10 (45%) males. 3 (14%) had stage I, 18 (82%) stage II, and 1 had an unspecified limited stage at initial diagnosis. Frontline therapy was chemotherapy alone in 19 (86%) and combined modality in 3 (14%). 21 (95%) received adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD), 17 (81%) with < 6 cycles. 14 (64%) had relapsed and 8 (36%) had refractory disease.

7 (32%) had CMR after pembro, 3 (14%) had PMR/SD with negative biopsy, 6 (27%) had PMR with positive biopsy, 1 (5%) had PMR without biopsy, and 5 (23%) had PD. 17 patients proceeded to ISRT, of whom 7 (41%) with CMR received 20 Gy, 3 (18%) with PMR/SD and negative biopsy received 30 Gy, and 7 (41%) with PMR/SD and positive/no biopsy received 36–40 Gy. Of the 14 with post-RT PET, 12 (86% of these patients, 67% overall) achieved CMR. After median follow up of 34 months (6–79), 2-year PFS was 65% (95% CI: 47–91).

Five patients progressed on pembro and three relapsed after a median of 12 months (range 7–70) from completion of pembro-RT. Among the patients with PD during or after pembro-RT, three are currently in remission, one is currently undergoing therapy, and the status for the others are unknown. Subsequent treatments included pembro plus gemcitabine/vinorelbine/liposomal doxorubicin followed by ASCT (n = 2), brentuximab vedotin (BV) plus nivolumab followed by ASCT (n = 1) and 2 doses of BV followed by additional RT (n = 1).

Immune-related toxicities were 3 (14%) grade 1 rash, and 3 (14%) grade 2 hypo/hyperthyroidism. Grade > 2 toxicities were 1 (5%) grade 3 headache, 1 (5%) grade 3 urinary tract infection, 1 (5%) grade 3 encephalopathy, and 1 (5%) grade 4 lipase elevation.

Conclusion: Pembro-RT yielded excellent CMR rates and minimal toxicity. These data suggest pembro-RT as a potential alternative to high dose chemo and SCT in localized, favorable relapsed/refractory HL.

Research funding declaration: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA provided drug and financial support for the study. NCT03179917.

Keywords: radiation therapy; Hodgkin lymphoma; immunotherapy

No potential sources of conflict of interest.

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一项多中心ii期研究：Pembrolizumab和放疗单独作为霍奇金淋巴瘤化疗后局部失败的替代移植

背景：化疗（chemo）后干细胞移植（SCT）是复发/难治性（RR）霍奇金淋巴瘤（HL）的标准治疗方法。在一项II期研究中，我们评估了派姆单抗（pembrolizumab, pembrolizumab）与相关部位放射治疗（ISRT）作为局部有利复发的替代挽救方法。方法：RR期IA/IIA患者，非笨重(<；1线治疗后进行PETCT模拟，随后进行pembroo 200mg IV q 21d，持续4个周期，3周后进行PETCT模拟。然后，患者接受ISRT治疗，每个反应如下：(1)20 Gy的完全代谢反应（CMR），由多维尔评分（DS） 1 - 3定义；(2)部分代谢反应（PMR）或稳定疾病（SD）（DS 4-5）和活检阴性患者30 Gy；(3) PMR/SD和活检阳性36-40 Gy。进展患者（PD）退出研究。在ISRT后4-6周记录PETCT反应。主要终点为pembrom - rt后的CMR率。次要终点是对单药pembro的反应、2年无进展生存期（PFS）和毒性。结果：22例患者中有22例入组，中位年龄36岁（22 - 66岁），10例（45%）为男性。3例（14%）为I期，18例（82%）为II期，1例在初始诊断时未明确限定期。一线治疗为单独化疗19例（86%），联合化疗3例（14%）。21例（95%）接受阿霉素、博来霉素、长春碱和达卡巴嗪（ABVD）治疗，17例（81%）接受<；6个周期。14例（64%）复发，8例（36%）难治性疾病pembroo后出现CMR(32%)，活检阴性的PMR/SD 3例（14%），活检阳性的PMR 6例（27%），无活检的PMR 1例（5%），PD 5例（23%）。17例患者进行ISRT，其中CMR组7例（41%）接受20 Gy， PMR/SD组3例（18%）活检阴性接受30 Gy， PMR/SD组7例（41%）活检阳性/无活检接受36-40 Gy。在14例接受rt后PET治疗的患者中，12例（86%的患者，67%的患者）达到了CMR。中位随访34个月（6-79）后，2年PFS为65% （95% CI: 47-91）。5名患者接受pembroo治疗进展，3名患者在完成pembroo - rt治疗后的中位12个月（范围7-70）复发。在pembrom - rt期间或之后的PD患者中，目前有3人处于缓解期，1人正在接受治疗，其他患者的状态未知。随后的治疗包括pembroo +吉西他滨/长春瑞滨/阿霉素脂质体，随后进行ASCT (n = 2), brentuximab vedotin (BV) + nivolumab，随后进行ASCT （n = 1）和2剂BV，随后进行额外的RT （n = 1）。免疫相关毒性为3例（14%）1级皮疹，3例（14%）2级甲状腺功能减退/亢进。年级比;2例毒副反应分别为1例（5%）3级头痛、1例（5%）3级尿路感染、1例（5%）3级脑病和1例（5%）4级脂肪酶升高。结论：pembrom - rt具有良好的CMR率和最小的毒性。这些数据表明，对于局部、有利的复发/难治性HL， pembrom - rt是高剂量化疗和SCT的潜在替代方案。研究经费声明：Merck Sharp &；Dohme LLC是默克公司的子公司；公司，Inc., Rahway， NJ， USA为研究提供了药物和资金支持。NCT03179917。关键词：放射治疗；霍奇金淋巴瘤;没有潜在的利益冲突来源。

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来源期刊

Hematological Oncology 医学-血液学

CiteScore

4.20

自引率

6.10%

发文量

147

审稿时长

>12 weeks

期刊介绍： Hematological Oncology considers for publication articles dealing with experimental and clinical aspects of neoplastic diseases of the hemopoietic and lymphoid systems and relevant related matters. Translational studies applying basic science to clinical issues are particularly welcomed. Manuscripts dealing with the following areas are encouraged: -Clinical practice and management of hematological neoplasia, including: acute and chronic leukemias, malignant lymphomas, myeloproliferative disorders -Diagnostic investigations, including imaging and laboratory assays -Epidemiology, pathology and pathobiology of hematological neoplasia of hematological diseases -Therapeutic issues including Phase 1, 2 or 3 trials as well as allogeneic and autologous stem cell transplantation studies -Aspects of the cell biology, molecular biology, molecular genetics and cytogenetics of normal or diseased hematopoeisis and lymphopoiesis, including stem cells and cytokines and other regulatory systems. Concise, topical review material is welcomed, especially if it makes new concepts and ideas accessible to a wider community. Proposals for review material may be discussed with the Editor-in-Chief. Collections of case material and case reports will be considered only if they have broader scientific or clinical relevance.