Hematological Oncology | 2019
Brentuximab vedotin and anti‐PD1 treatment optimize survival in chemo‐refractory Hodgkin lymphoma patients: Real‐world data
Abstract
Dear Editor, Brentuximab vedotin (BV) and anti-PD1 treatment have been assigned to chemo-refractory Hodgkin lymphoma treatment. Impact of these agents on overall survival (OS) after autologous hematopoietic cell transplantation (AHCT) remains under investigation. In this real-world data study, we aimed to compare long-term outcomes of AHCT in patients treated with BVand/or anti-PD1 to a historical control group. We retrospectively recorded clinical characteristics and outcomes of chemo-refractory Hodgkin lymphoma patients who underwent AHCT in our JACIE (Joint Accreditation Committee-ISCT & EBMT) accredited Unit during 2011-2017. Data from historical controls were retrieved from a previous dataset. Our institutional review board and ethics committee of G. Papanicolaou Hospital approved this study. All patients gave written informed consent, and the study was conducted in accordance with the Helsinki Declaration. We studied a total of 56 patients (33 men:23 women, median age 37 years old, 19-65) treated with BV: 26 pre-transplant, 30 posttransplant. Among them, seven patients received BV both preand post-transplant. The majority of pre-transplant BV patients had primary refractory disease or early relapse (92%). Post-transplant treatment occurred in the context of relapsed/ refractory disease in 27 patients; BV allowed 12 (40%) patients to successfully go through an allogeneic stem cell transplant post reducedintensity conditioning without additional toxicities. Among them, six had additional chemotherapy and two anti-PD1 treatment, gaining a complete metabolic response (CMR). In the rest of patients, treatment was changed due to eventual BV failure. BV was administered as a consolidation treatment in 10 patients, as previously reported in the AETHERA study. In six of them, BV had already been administered before transplant as well. Out of consolidation treatment patients, two relapsed and subsequently received anti-PD1 treatment. In total, two patients died due to prior chemotherapy complications, whereas 13 are currently on anti-PD1 treatment. PET-based response was available in six patients, four having a CMR and two a partial metabolic response. Stable disease was achieved by CT-based response in the rest patients. No major toxicities were observed. One patient presented with grade 2 asymptomatic hypothyroidism and one with grade 3 anemia attributed to noninflammatory upper gastrointestinal blood loss. Figure 1 summarizes a treatment disposition flow for patients treated with BV. In total, 20 patients received anti-PD1 checkpoint inhibitors treatment. With a median follow-up of 34.3 (1.5-202.2) months, 5year OS was 65.9% in patients treated only with BV compared to 78.2% in patients treated with additional anti-PD1 treatment. Median OS for patients treated only with BV was 113.5 months, whereas median OS has not been reached for patients that received anti-PD1 treatment. Last, we compared patients treated with or without novel treatments. Historical controls comprised a group of 29 patients with chemo-refractory HL that underwent ASCT at relapse (n = 6) or partial remission (n = 23). Table S1 shows clinical characteristics of the three groups. There was no significant difference in basic clinical characteristics. Only 10% of the historical controls were eligible for allogeneic transplantation, compared to 26.5% of patients receiving BV and 20% of patients receiving BV and anti-PD1 treatment (p = 0.200). The latter presented significantly higher 10-year OS compared to patients treated with BV only or historical controls (67.3% versus 33% versus 29.7%, p = 0.044), as shown in Figure 2. No significant difference in disease-free survival was observed. Our comparative study clearly illustrates that the principles of management of relapsed or refractory HL have been improved in the era of novel interventions combined with or without allogeneic transplant in selected population. Our analysis provides the benefit of post-ASCT comparison of OS. Indeed, long-term OS has not been previously evaluated with checkpoint inhibitors which have shown excellent 6-month or 1-year OS up to 98.7%. The defined goal of BV plus anti-PD1 treatment on disease status improvement also reflects their impact on post allo-HCT outcomes. In this context, our data confirm that more patients underwent allo-HCT with the curative capacity in the anti-PD1 treatment group than in the BV alone group. Nevertheless, the use of anti-PD1 treatment as a bridge to allo-HCT has shed light to several issues of potential additional toxicity (sinusoidal obstruction syndrome or veno-occlusive disease, post-transplant hyperacute febrile syndrome, pneumonitis), and the most burning unanswered question remains the optimal wash out period from cessation of checkpoint inhibitors to transplant. The above considerations have not been mentioned for BV. Our study has some limitations. First, our study population is relatively small. Second, its retrospective non-randomized nature hinders safe comparisons among treatment arms. Third, we studied patients transplanted over a relatively long transplant period. Received: 3 June 2019 Accepted: 4 June 2019