Moskowitz Alison J, Schöder Heiko, Gavane Somali, Thoren Katie L, Fleisher Martin, Yahalom Joachim, McCall Susan J, Cadzin Briana R, Fox Stephanie Y, Gerecitano John, Grewal Ravinder, Hamlin Paul A, Horwitz Steven M, Kumar Anita, Matasar Matthew, Ni Andy, Noy Ariela, Palomba M Lia, Perales Miguel-Angel, Portlock Carol S, Sauter Craig, Straus David, Younes Anas, Zelenetz Andrew D, Moskowitz Craig H
Lymphoma Service and.
Nuclear Medicine Department, Memorial Sloan Kettering Cancer Center, New York, NY.
Blood. 2017 Nov 16;130(20):2196-2203. doi: 10.1182/blood-2017-06-788877. Epub 2017 Sep 5.
Identification of prognostic factors for patients with relapsed/refractory Hodgkin lymphoma (HL) is essential for optimizing therapy with risk-adapted approaches. In our phase 2 study of positron emission tomography (PET)-adapted salvage therapy with brentuximab vedotin (BV) and augmented ifosfamide, carboplatin, and etoposide (augICE), we assessed clinical factors, quantitative PET assessments, and cytokine and chemokine values. Transplant-eligible patients with relapsed/refractory HL received 2 (cohort 1) or 3 (cohort 2) cycles of weekly BV; PET-negative patients (Deauville score ≤2) proceeded to autologous stem cell transplantation (ASCT) whereas PET-positive patients received augICE before ASCT. Serum cytokine and chemokine levels were measured at baseline and after BV. Metabolic tumor volume (MTV) and total lesion glycolysis were measured at baseline, after BV, and after augICE. Sixty-five patients enrolled (45, cohort 1; 20, cohort 2); 49 (75%) achieved complete response and 64 proceeded to ASCT. Three-year overall survival and event-free survival (EFS) were 95% and 82%, respectively. Factors predictive for EFS by multivariable analysis were baseline MTV (bMTV) ( < .001) and refractory disease ( = .003). Low bMTV (<109.5 cm) and relapsed disease identified a favorable group (3-year EFS, 100%). For patients who received a transplant, bMTV and pre-ASCT PET were independently prognostic; 3-year EFS for pre-ASCT PET-positive patients with low bMTV was 86%. In this phase 2 study of PET-adapted therapy with BV and augICE for relapsed/refractory HL, bMTV and refractory disease were independent prognostic factors for EFS. Furthermore, bMTV improved the predictive power of pre-ASCT PET. Future studies should optimize efficacy and tolerability of salvage therapy by stratifying patients according to risk factors such as bMTV.
确定复发/难治性霍奇金淋巴瘤(HL)患者的预后因素对于采用风险适应性方法优化治疗至关重要。在我们的2期研究中,采用了以正电子发射断层扫描(PET)为导向的挽救性治疗方案,使用了本妥昔单抗(BV)以及强化异环磷酰胺、卡铂和依托泊苷(augICE),我们评估了临床因素、PET定量评估以及细胞因子和趋化因子值。符合移植条件的复发/难治性HL患者接受了2个周期(队列1)或3个周期(队列2)的每周一次BV治疗;PET阴性患者(Deauville评分≤2)进行自体干细胞移植(ASCT),而PET阳性患者在ASCT前接受augICE治疗。在基线和BV治疗后测量血清细胞因子和趋化因子水平。在基线、BV治疗后和augICE治疗后测量代谢肿瘤体积(MTV)和总病变糖酵解。65名患者入组(队列1为45名;队列2为20名);49名(75%)实现完全缓解,64名患者进行了ASCT。三年总生存率和无事件生存率(EFS)分别为95%和82%。多变量分析预测EFS的因素为基线MTV(bMTV)(P<0.001)和难治性疾病(P = 0.003)。低bMTV(<109.5 cm³)和复发性疾病确定为一个良好组(三年EFS,100%)。对于接受移植的患者,bMTV和ASCT前PET具有独立的预后意义;ASCT前PET阳性且bMTV低的患者三年EFS为86%。在这项关于BV和augICE用于复发/难治性HL的PET适应性治疗的2期研究中,bMTV和难治性疾病是EFS的独立预后因素。此外,bMTV提高了ASCT前PET的预测能力。未来的研究应通过根据bMTV等风险因素对患者进行分层来优化挽救性治疗的疗效和耐受性。