pembrolizumab用于brentuximab治疗失败的淋巴瘤    
2017年04月21日
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2016年7月18日最近的I期临床试验证实,pembrolizumab (Keytruda)对brentuximab vedotin (Adcetris)治疗效果不佳的经典霍奇金淋巴瘤可达到65%的反应率。

Early Results Find Pembrolizumab Active in Classical Hodgkin Lymphoma After Brentuximab Vedotin Failure

Key Points

◆ Pembrolizumab had an acceptable safety profile in patients with classical Hodgkin lymphoma progressing on or after brentuximab vedotin treatment.

◆ Response was achieved in 65% of patients, and further study is warranted.

Findings in a classical Hodgkin lymphoma cohort in the phase Ib KEYNOTE-013 trial, reported by Armand et al in the Journal of Clinical Oncology, indicate that pembrolizumab (Keytruda) is active in patients with disease progressing on or after brentuximab vedotin (Adcetris) treatment.

Study Details

The study included 31 patients with relapsed or refractory Hodgkin lymphoma progressing on or after brentuximab vedotin treatment. Patients received pembrolizumab at 10 mg/kg every 2 weeks until disease progression or unacceptable toxicity. Overall, 55% of patients had at least four lines of prior therapy, and 71% had relapsed after autologous stem cell transplantation.

Toxicity

The most common treatment-related adverse events of any grade were hypothyroidism (16%), diarrhea (16%), nausea (13%), and pneumonitis (10%). Grade 3 treatment-related adverse events occurred in five patients (16%) and consisted of colitis, increased alanine transaminase and aspartate transaminase, nephrotic syndrome, joint swelling, back pain, and axillary pain.

No grade 4 adverse events or treatment-related deaths were observed. Two patients discontinued treatment, due to grade 2 pneumonitis and grade 3 nephrotic syndrome.

Responses

Response occurred in 20 patients (65%), including complete remission in 5 (16%). Responses persisted for at least 24 weeks in 70% of responders. At a median follow-up of 17 months, response durations ranged from 0.14+ to 74+ weeks. Progression-free survival was 69% at 24 weeks and 46% at 52 weeks.

A high prevalence of PD-L1 (programmed cell death ligand 1) and PD-L2 (programmed cell death ligand 2) expression; treatment-induced expansion of T cells and natural killer cells; and activation of interferon-γ, T-cell receptor, and expanded immune-related signaling pathways were observed on biomarker analysis.

The investigators concluded: “Pembrolizumab was associated with a favorable safety profile. Pembrolizumab treatment induced favorable responses in a heavily pretreated patient cohort, justifying further studies.”


参考资料:
http://www.ascopost.com/News/42755



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