Response to Brentuximab Vedotin and Quality of Life in Patients with Relapsed/Refractory Hodgkin Lymphoma (RR HL) in the Real World Setting

Abstract

There is a continued unmet medical need in pts with relapsed/refractory Hodgkin's lymphoma (RR HL). Curing HL pts who have refractory disease after salvage chemotherapy, who relapse after ASCT, or those who are not candidates for ASCT, remains a clinical challenge due to limited effective treatments. There are data available indicating that brentuximab vedotin (BV) brings considerable promise for the treatment of pts with RR HL. Information about BV treatment effectiveness and tolerability both from physician's and patient's perspective is worthwhile in this difficult patient population. We aimed to evaluate clinical and patient-reported outcomes in RR HL patients receiving BV as >2nd treatment line. Here we report the outcomes with respect to clinical response, tolerability, quality of life (QoL) and symptoms after 3 mos of BV treatment. The total number of pts to be included in the multicenter observational real-world study is 70 pts with RR HL who received BV 1.8 mg/kg q3w till disease progression, intolerance toxicity of BV or refusal. Treatment response was assessed using RECIST criteria v. 1.0. Adverse events (AEs) were assessed in accordance with NCI CTCAE v. 4.03. For QoL assessment pts filled out RAND SF-36, for symptom assessment - ESAS questionnaire; also pts filled out PGIC scale for self-assessment of changes in their health. For QoL analysis paired t-test, Mann-Whitney test, Wilcoxon test and χ2 were used. The analysis was performed in the group of 55 pts RR HL (median age - 28 years, range 18-67, 54.5% males) who were involved in the study: 63.6% pts had advanced stage (III-IV) at diagnosis; ≥50% pts had B-symptoms (58.2%); 82% pts - ECOG 0-1. All the pts received a median of 3 previous treatment lines; among them 14 pts (25.5%) failed to ASCT in the past; half of pts were primary chemotherapy resistant (49%). Before BV treatment start QoL was dramatically worsened for all SF-36 scales (p<0.05). All the pts experienced symptoms, 83.3% pts had moderate-to-severe symptoms. The most frequent (>70% pts) symptoms were drowsiness, tiredness, anxiety, and worse wellbeing. More than half pts had moderate-to-severe drowsiness,tiredness, depression, lack of appetite and worsened wellbeing before BV treatment start. After 3 mos of BV treatment objective response was registered in 55% pts with 27.5% complete response. Adverse events of grade I-II were reported in 8 pts (20%) and were consistent with known toxicities. Most common adverse events (≥10%) were increasing ALT and AST (each 4/8), peripheral neuropathy, fatigue, skin itch (each 3/8). Severe adverse event (III grade) not related with BV occurred in one patient (2.5%) - sepsis, respiratory insufficiency due to agranulocytosis (BV was temporary stopped). During BV treatment meaningful QoL improvement was revealed for all SF-36 scales (p<0.05), excluding mental health. IQoLI significantly increased at 3 mos after treatment start as compared to baseline: 0.260 at baseline vs 0.390 at 3 mos (p<0.001). Proportion of pts with significant Integral QoL Index (IQoLI) impairment dramatically decreased during treatment as compared to baseline: 60% before treatment vs 35% at 3 mos (χ2, p=0.05). The most pronounced meaningful improvement was revealed for role functioning scales (∆>20.0). The severity of the vast majority of symptoms excluding depression significantly decreased during 3 mos of treatment (p<0.05). Total Symptom Score by ESAS significantly decreased at 3 mos after BV treatment start (35.8 vs 25.4, p=0.001). Also according to PGIC, 90% pts noted the improvement of their health. The first results obtained in this multicenter observational real world study demonstrate notable activity of BV as a treatment modality for RR HL. BV showed a safety profile consistent with known toxicities. BV treatment was accompanied with dramatic QoL improvement and significant decrease of symptom burden already after 3 mos of treatment. Evaluation of BV treatment outcomes both from physician's and patient's perspective may provide unique information which will be helpful in decision making for patients with RR HL. Disclosures Ionova: Takeda, BMS: Other: Principal Investigator of IISR, Research Funding. Baryakh:Takeda: Consultancy, Honoraria, Speakers Bureau.

Effectiveness of brentuximab vedotin monotherapy in relapsed or refractory Hodgkin lymphoma: a systematic review and meta-analysis

“…Similar results were observed for the CR rate (34% in the clinical trial versus 33.4% in the meta-analysis) [4]. In the pivotal phase II trial, the study population was restricted to patients with an ECOG performance status score of 0 or 1, while some observational studies included patients with ECOG PS 2 or higher [16,24]. Also, patients with previous allogeneic SCT were excluded from the trial, whereas several studies identified in the systematic review included patients with such history of transplantation [14,21,[25][26][27]29,37].…”

“…In these studies, the study populations were representative of patients who are eligible to BV, according to the approved indication. Specifically, the proportion of patients who received previous ASCT ranged from 25.5% [24] to 100% [8,17,36] and 37.5% [27] to 81% [42] patients had refractory HL, defined as stable or progressive disease during first-line or salvage chemotherapy. However, almost half studies (n ¼ 10; 41.7%) did not provide any details regarding the distribution of patients according to relapse or…”

“…Seven of these 12 studies were deemed of good methodological quality [8,14,15,20,22,28,36] and were included in the primary meta-analysis while the remaining five studies were of moderate methodological quality and hence, were only considered for the sensitivity analyses [16,21,26,27,41]. In addition, there were 14 studies which consisted of abstracts or conference proceedings that were included in a second set of sensitivity analyses [17][18][19][23][24][25][29][30][31][32]34,38,39,42].…”