Dagogo-Jack Ibiayi, Lasko Aubrey, Krueger Elizabeth A, Tsang Kitman, Rao Revati, Hambelton Grace, Digumarthy Subba R
Massachusetts General Hospital Cancer Center, Boston, Massachusetts.
Harvard Medical School, Boston, Massachusetts.
JTO Clin Res Rep. 2024 Nov 22;6(5):100775. doi: 10.1016/j.jtocrr.2024.100775. eCollection 2025 May.
Chemoimmunotherapy is associated with promising activity in mesothelioma in phase II to III trials. Studies exploring this approach in patients ineligible for clinical trials are lacking. We assembled a cohort of patients receiving pemetrexed-based chemotherapy with durvalumab outside of clinical trials.
Patients with pleural mesothelioma received pemetrexed plus durvalumab or carboplatin plus pemetrexed plus durvalumab via off-label authorization at Massachusetts General Hospital. Response to chemoimmunotherapy was assessed per modified Response Evaluation Criteria in Solid Tumors version 1.1. A retrospective chart review was conducted to assess safety per Common Terminology Criteria for Adverse Events version 5.0.
Twelve patients were included in the series. Nine patients were treated with triplet chemoimmunotherapy. Three patients received doublet chemoimmunotherapy because of platinum ineligibility. Concurrent active malignancies and symptomatic cardiac disease were present in three patients (25%) and two patients (17%), respectively. Ten patients had measurable disease at baseline. With the triplet regimen, partial responses were observed in four of the seven (57%) patients with measurable disease. All three patients receiving pemetrexed plus durvalumab had measurable disease and experienced a partial response. Primary progression was not observed with either regimen. Overall, eight patients (75%) remained on treatment for more than 6 months without progression. Five patients developed immune-related adverse events (n = 1 each pyrexia, arthritis, neutropenia, Raynaud's disease, stomatitis). Three patients discontinued treatment because of toxicity or symptomatic comorbid conditions (n = 1 grade 3 heart failure, n = 1 grade 2 fever + progressive kidney cancer, n = 1 grade 2 fatigue).
Antitumor activity of chemoimmunotherapy reported in phase II to III clinical trials is generalizable to the broader patient population with mesothelioma. However, the tolerability of chemoimmunotherapy is impacted by comorbid conditions in real-world patients.
在II期至III期试验中，化学免疫疗法在间皮瘤治疗中显示出有前景的活性。目前缺乏针对不符合临床试验条件的患者探索这种治疗方法的研究。我们收集了一组在临床试验之外接受培美曲塞联合度伐利尤单抗化疗的患者。
胸膜间皮瘤患者在麻省总医院通过非标签用药授权接受培美曲塞加度伐利尤单抗或卡铂加培美曲塞加度伐利尤单抗治疗。根据实体瘤疗效评价标准（mRECIST）1.1版评估化学免疫疗法的反应。通过回顾性病历审查，根据不良事件通用术语标准（CTCAE）5.0版评估安全性。
该系列纳入了12例患者。9例患者接受三联化学免疫疗法。3例患者因不适合使用铂类药物而接受双联化学免疫疗法。分别有3例患者（25%）和2例患者（17%）同时存在活动性恶性肿瘤和有症状的心脏病。10例患者基线时有可测量病灶。采用三联方案时，7例有可测量病灶的患者中有4例（57%）观察到部分缓解。所有3例接受培美曲塞加度伐利尤单抗治疗的患者均有可测量病灶并出现部分缓解。两种方案均未观察到原发性进展。总体而言，8例患者（75%）持续治疗超过6个月且无进展。5例患者出现免疫相关不良事件（发热、关节炎、中性粒细胞减少、雷诺病、口腔炎各1例）。3例患者因毒性或有症状的合并症而停止治疗（1例3级心力衰竭、1例2级发热+进展性肾癌、1例2级疲劳）。
II期至III期临床试验中报道的化学免疫疗法的抗肿瘤活性可推广至更广泛的间皮瘤患者群体。然而，在现实世界的患者中，合并症会影响化学免疫疗法的耐受性。
