Brentuximab Vedotin Consolidation Research Articles

Brentuximab vedotin plus cyclophosphamide, doxorubicin, etoposide, and prednisone followed by brentuximab vedotin consolidation in CD30-positive peripheral T-cell lymphomas: a multicentre, single-arm, phase 2 study

CD30 expression is universal in anaplastic large-cell lymphoma and is expressed in some other peripheral T-cell lymphoma subtypes. Incorporation of brentuximab vedotin into initial therapy for people with CD30-positive peripheral T-cell lymphomas prolonged progression-free survival, but there is room for improvement, especially for people with non-anaplastic large-cell lymphoma subtypes. We conducted a multicentre, international, single-arm, phase 2 trial to evaluate the safety and activity of CHEP-BV (cyclophosphamide, doxorubicin, prednisone, brentuximab vedotin, and etoposide) followed by brentuximab vedotin consolidation in patients with CD30-expressing peripheral T-cell lymphomas across five academic centres in the USA and Canada. Adults aged 18 years or older with newly diagnosed, untreated CD30-positive peripheral T-cell lymphomas, Eastern Cooperative Oncology Group score of 0-2, and adequate organ function were eligible to receive six planned cycles of CHEP-BV (ie, 1·8 mg/kg brentuximab vedotin intravenously on day 1, cyclophosphamide 750 mg/m2 intravenously on day 1, doxorubicin 50 mg/m2 intravenously on day 1, etoposide 100 mg/m2 daily intravenously on days 1-3, and prednisone 100 mg daily orally on days 1-5) with prophylactic G-CSF. Patients who responded to the treatment could receive brentuximab vedotin consolidation for up to ten additional cycles either after autologous haematopoietic stem-cell transplantation (HSCT) or directly after CHEP-BV. The primary endpoints were unacceptable toxicity during a 3-plus-3 safety lead-in in participants who received study treatment and completed the safety evaluation period (to confirm the recommended phase 2 dose of brentuximab vedotin in CHEP-BV) and the complete response rate after CHEP-BV induction therapy in participants who received study treatment and had response evaluation. The study was registered at ClinicalTrials.gov (NCT03113500), and this cohort completed the trial. The trial is ongoing with the enrolment of a new cohort. 54 patients were screened for eligibility and 48 were eligible for the study. The participants (18 [38%] women and 30 [63%] men; 34 [71%] White, four [8%] Black, five [10%] Asian, ten [21%] Hispanic, and 37 [77%] non-Hispanic people) were recruited and enrolled between Dec 4, 2017, and June 14, 2021, and followed up until Aug 25, 2023, when the database was locked for analysis. 48 participants were evaluable for toxicity, and 47 were evaluable for response (one participant died from COVID-19 before response assessment). During the safety lead-in, one of six participants had an unacceptable toxicity (ie, platelet count <10 000 per mm3 in a participant with extensive bone marrow involvement), and the proposed phase 2 dose of 1·8 mg/kg brentuximab vedotin in CHEP-BV was confirmed. At completion of CHEP-BV, 37 of 47 participants had complete response, yielding a complete response rate of 79% (95% CI 64-89). The most common CHEP-BV-related toxicities of grade 3 or higher were neutropenia (14 [29%] of 48), leukopenia (11 [23%]), anaemia (ten [21%]), febrile neutropenia (ten [21%]), lymphopenia (nine [19%]), and thrombocytopenia (nine [19%]). There were no treatment-related deaths. In patients with mostly CD30-expressing peripheral T-cell lymphomas other than non-anaplastic large-cell lymphoma, CHEP-BV (with or without autologous HSCT) followed by brentuximab vedotin consolidation was safe and active. SeaGen, Leukemia and Lymphoma Society, Lymphoma Research Foundation, and the National Cancer Institute of the National Institutes of Health.

Etoposide addition and brentuximab vedotin consolidation in first-line treatment of CD30-positive peripheral T-cell lymphoma: can we improve BV–CHP?

Etoposide addition and brentuximab vedotin consolidation in first-line treatment of CD30-positive peripheral T-cell lymphoma: can we improve BV–CHP?

PD-1 Blockade before Autologous Stem Cell Transplantation Improves Outcomes in Relapsed/Refractory Classic Hodgkin Lymphoma: Results from a Multicenter Cohort

Introduction: Single arm studies incorporating PD-1 blockade and/or brentuximab vedotin (BV) to salvage regimen have produced encouraging results in transplant-eligible relapsed/refractory classic Hodgkin lymphoma (R/R cHL) and are increasingly used in practice. As prospective randomized studies comparing PD1 based salvage to other salvage regimens are lacking, we conducted a retrospective study comparing post-transplant outcomes of R/R cHL patients who received PD1-based regimen and other novel and conventional regimen. Methods: Consecutive adult patients with R/R cHL who received salvage therapy and underwent autologous stem cell transplant (ASCT) between 2010 and 2021 at 5 United States academic institutions were included. Demographics and clinical variables were recorded at relapse by electronic health records review. Study Objectives were post-ASCT progression free survival (PFS) and overall survival (OS). Results: 981 pts of R/R cHL were identified. At relapse, median age was 31 (IQR: 21-43) years, 504 (52%) were male, 323 (49%) had advanced stage, 353 (41%) had extranodal disease (END), 185 (22%) had B symptoms, 345 (45%) were refractory to frontline therapy and 317 (32%) relapsed within a year of frontline therapy.308 (31%) received &amp;gt;1 line of salvage before ASCT. Patients were divided into 3 groups based on salvage therapy received: 1) 195 (20%) patients received a PD-1 agent with or without BV at any point before ASCT (PD-1 group), 2) 312 (32%) patients received BV at any point before ASCT without PD-1 (BV group), and 3) 474 (48%) patients received no novel agent before ASCT (chemo group). PFS was significantly higher in PD1 group (2-yr PFS 93.1 (CI 95: 89.4-96.9)%); compared to BV (2 yr PFS 73.9 (CI 95: 69.1-79.1)% , p &amp;lt;0.0001) or chemo groups (2 yr PFS 71.6 (CI 95: 67.6-75.9)% , p&amp;lt;0.0001). PFS was not different between the BV and chemo groups (p=0.88) (Figure 1). OS was not significantly different between PD-1 group (2 yr OS 96.2 % (CI 95: 93.2-99.2), p=0.06), BV group (2 yr OS 94.3% (CI 95: 91.7-97.0), p=0.2) and chemo group (2 yr OS 91.8% (CI 95: 89.3-94.4)). Amongst pts who were transplanted in complete metabolic response (CMR), we assessed post-ASCT PFS and OS based on salvage therapy received immediately before ASCT. Pts who received PD-1 as last salvage therapy had improved PFS compared to chemo (HR: 0.15 (CI 95: 0.07-0.3), p= &amp;lt;0.0001) and BV (HR: 0.2 (CI 95: 0.08-0.5), p= &amp;lt;0.001). Pts receiving PD-1 immediately before ASCT also had higher OS compared to those receiving chemo (HR: 0.2 (CI 95: 0.05-0.8), p= 0.02) but not BV (HR: 0.8 (CI 95: 0.4-1.3), p=0.1). There was no difference between BV and chemo group in regards to PFS and OS. In multivariable analysis that included time to relapse, B symptoms, END, pre-ASCT response, number of salvage therapy lines before ASCT, year of transplant and BV consolidation, PD-1 salvage therapy had significantly higher PFS compared to chemotherapy (HR: 0.3 (CI 95: 0.2-0.5), p= &amp;lt;0.001). BV group had significantly lower PFS (HR: 3.34 (CI 95: 1.8-6.0), group=0.002) compared to PD1 group. PFS was not different between BV and chemo group (p= 0.7). OS was similar between all 3 groups. Similar PFS and OS were seen among patients receiving PD-1 + BV (n=83) and PD-1 with or without chemo (n =112) (p=0.96 for PFS; p= 0.72 for OS); as well as for patients receiving PD-1 as part of their first salvage therapy (n=151) or later salvage treatments (n=44) (p=0.45 for PFS, p= 0.3 for OS). Patients who received PD1 based regimen as last salvage therapy pre-ASCT had significantly better PFS (HR: 6.8 (CI 95: 2.4-19.2), p= &amp;lt;0.0001) and OS (HR: 10.6 (CI 95: 2.5-44.8), p= 0.0001) compared to patients who received PD1 prior to their last line of salvage therapy per-ASCT. Conclusion: Receipt of PD-1 based salvage therapy at any point before ASCT is associated with significantly improved PFS compared to either BV or chemotherapy-based salvage treatments. In the subgroup of patients transplanted in CMR, PD1 based last salvage regimen were associated with higher PFS compared to chemotherapy and BV and higher OS compared to chemotherapy. PD1 based last salvage therapy pre-ASCT was associated with better survival compared to PD1 prior to last salvage therapy. Results of this study strongly support the use of PD-1 based salvage therapy for patients with R/R cHL. S.D., R.M., H.S contributed equally. R.S., M.M. contributed equally.

Real Life Analysis of Brentuximab Vedotin (BV) Use As Consolidation Therapy in Patients with Hodgkin's Lymphoma (HL) with High Risk of Relapse after Autologous Stem Cell Transplantation (ASCT). a Retrospective Analysis of the EBMT Lymphoma Working Party

Introduction: The gold standard treatment for patients (pts) with classical HL who fail first-line treatment is ASCT. However, a significant number of pts with high-risk relapsed/refractory (RR) HL will relapse after transplant. Most patients who relapse do so within the first 1-3-years following ASCT, providing a rationale for post-transplant consolidation strategies to mitigate relapse risk. The AETHERA trial demonstrated that post-ASCT consolidation with brentuximab vedotin (BV) in high-risk HL pts improved progression-free survival (PFS) compared to placebo. Three previous studies have reported real-life results of BV consolidation with similar results. Here, we present the largest series so far. Methods: Information of pts older than 18y with HL who received BV as consolidation after first ASCT between May 2016 and January 2021 was downloaded from the EBMT database. The decision to use BV consolidation was made by the attending physician on an individual basis. Patients who received BV for disease relapse after ASCT were excluded from the study. The primary endpoint was 2 year PFS from ASCT. Results: 309 pts (female 48%/male 52%) with HL were identified meeting the inclusion criteria. Median age at ASCT was 31y (18-70). The median number of therapy lines before ASCT was 2 (1-6), and 43% pts required >1 salvage treatment to achieve disease response. At the time of ASCT, 200 (66%) pts were in complete remission (CR), 81 (27%) in partial remission (PR), and 21 (7%) had refractory disease. Most pts (73%) received BEAM as conditioning regimen. Median time from ASCT to BV initiation was 2.2 months (0.1-16.7). A total of 55 (19%) pts relapsed after a median time of 8 months after BV initiation, and 24 of them were treated with an allogeneic transplantation. After a median follow-up of 20 months, 2 and 5-year PFS were 73.2% (95% CI 67.3-79.6) and 70.3% (95% CI 63.9-77.4) (Figure 1), and overall survival 95.1% (95% CI 92.1-98.2) and 91.3% (95% CI 86.7-96.1), respectively. The prognostic was excellent and significantly better for pts in CR at transplant than for those in PR or with progression disease (2-y PFS 83.5% [95%CI 77.3-90.2] vs. 57.2% [95% CI 45.6-71.8] and 63.6% [95% CI 45.3-89.5], respectively, p=0.001). No differences in OS were observed according to the disease status at ASCT. In comparison to AETHERA trial, the proportion of pts requiring >1 salvage therapy lines before transplant was similar (43% in both studies); however, in contrast to that trial, pts treated with >1 salvage therapy line had similar PFS than those treated with only one line (69.6% [95%CI 60.4-80.2] vs. 75.8% [95%CI 68.5-84.0], respectively, p=0.2). In our study, the number of pts with chemosensitive disease at ASCT was higher than in the AETHERA (93% vs. 72% CR + PR, and 66% vs. 37% CR). This fact could justify that the PFS observed in this real-life series was higher than this of the AETHERA trial (70.3% vs. 59%) and more similar to that reported in other real-life series. Conclusions: This EBMT-registry study confirms the improved PFS of RR HL pts who underwent ASCT followed by BV consolidation compared to historical cohorts. The proportion of patients receiving ASCT in CR is higher than published in the AETHERA trial, which would suggest that more effective pre-transplant salvage schemes, possibly including BV, have been used. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Impact of pre- and/or post-autologous stem cell transplantation exposure to brentuximab vedotin on survival outcomes in patients with high-risk Hodgkin lymphoma.

The AETHERA trial demonstrated that brentuximab vedotin (BV) consolidation after autologous stem cell transplantation (ASCT) in patients with Hodgkin lymphoma (HL) at high risk of relapse/progression increases progression-free survival (PFS). Patients previously exposed to BV were excluded from that trial. However, BV alone or in combination with chemotherapy is frequently used as front-line treatment and/or pre-ASCT salvage therapy. We analyzed data from 156 patients with high-risk HL who underwent ASCT with (BV-CON, n = 62) or without (non-BV, n = 94) BV consolidation. Fifty-seven patients received BV-based salvage regimens before ASCT. The 3-year overall survival and PFS for all patients were 91.6% and 70.0%, respectively. Multivariate analysis showed that BV-CON was associated with better PFS (HR 0.39, p = 0.01), whereas positive PET at transplant leaded to worse PFS (HR 2.71, p = 0.001). BV-CON improved PFS in PET-positive patients (72.2% vs. 43.0%, p = 0.05), with a beneficial trend observed in PET negative (88.8% vs. 75.2%, p = 0.09). BV-CON patients with or without BV exposure pre-ASCT had a significantly better PFS than non-BV with or without BV pretransplant treatment (HR 0.36, p = 0.004). The efficacy of real-life BV consolidation therapy was similar to that in the AETHERA trial. This therapeutic strategy improves survival independently of BV exposure prior to ASCT.

P104: Consolidation Therapy with Brentuximab Vedotin after Autologous Stem Cell Transplantation for Relapsed/Refractory Hodgkin Lymphoma in the Czech Republic.

Figure 1: Progression-free survival figure, N=39 pts Introduction: Consolidation therapy with brentuximab vedotin (BV) following autologous stem cell transplantation (ASCT) has demonstrated improved progression-free survival (PFS) in high-risk patients (pts) with relapsed/refractory classic Hodgkin lymphoma (cHL) in the AETHERA trial. We have analysed data from seven centres of intensive haematological care in the Czech Republic between January 2015 and December 2021 based on real-life experience with the treatment. The primary goals included basic statistical decription, assessment of the PFS and toxicity of the treatment. Patients and Methods: All of the pts were treated with high-dose chemotherapy and ASCT in the first relapse, all had at least one of the risk factors as per AETHERA and no previous treatment with BV. We have analysed 39 pts treated with BV 1.8 mg/kg i.v. every 3 weeks for a maximum of 16 cycles. Results: Median age was 37 years (range 19–65) at the time of the first dose of BV. Nearly 80% of pts were initially treated as advanced stage cHL and eBEACOPP was administered in 59% of pts in the frontline setting. Primary refractory or early relapsed (within 12 months after the frontline therapy) cHL pts represented 69% of the analysed cohort. Two different salvage regimens were administered in 30.8% and failure to achieve a complete response (CR) after salvage chemotherapies prior ASCT was seen in 64% of pts. The median number of BV administered was 8 (1–16), with 16 completed cycles in 20.5% pts. Main reasons for early discontinuation were neuropathy and relapsed or progressive disease, both in 15.4%. Overall, 82% of pts achieved CR during the treatment. With a median follow-up 28 months the 2-year PFS was 66.2% (95% CI 0.52–0.85) and the 2-year overall survival was 95% (95% CI 0.82–1.00). Two pts died, one of progressive lymphoma and one of severe bacterial infection. Peripheral sensory neuropathy occurred in 38.5% (grade 3–4 in 10.3%), neutropenia in 28.2% (grade 3–4 in 17.9%) and respiratory infections in 28.5% (grade 3–4 in 2.6%). Discussion: Despite some differences in the analysed groups, our results are comparable with a few real-world data published lately and support the notion that BV consolidation improves PFS in patients with at least one risk factor for subsequent relapse of cHL and has a feasible and manageable toxicity. Supported by following grants MH CZ – DRO (FNOl, 00098892) AZV NU22-03-00182

Cost-effectiveness of brentuximab vedotin in treating increased risk of relapse/progression of classical hodgkin lymphoma patients post autologous stem cell transplant

Objective: Hodgkin lymphoma patients who relapsed/progressed early after autologous stem cell transplant (ASCT) usually have poor prognoses. Results from clinical trials have demonstrated Brentuximab vedotin (BV)’s significant clinical effectiveness for consolidation therapy after ASCT for patients who have high risk of relapse/progress. An economic evaluation study for Vietnamese CHL patients is necessary and can provide useful evidence for policymakers. Methods: A multi-stage economic evaluation model consisting of two partitioned survival models was used to estimate incurring costs and effectiveness from health insurance perspective for two hypothetical groups of Vietnamese adult CHL patients who have high risk of relapse/progression, one received standard care and the other received BV consolidation plus standard care as post-ASCT care. Necessary healthcare services were identified via Ministry of Health guidelines and Vietnamese clinical opinions. Efficacy parameters were taken from published systematic review and randomized controlled trials results. Model costs and utility inputs were adapted for Vietnamese context via relevant published literature, guidelines, regulations, and clinical opinions. Model cycle of 1 week and life-time horizon was used. Discounting rate of 3% was applied for cost and effectiveness. Results: Consolidation with BV post-ASCT was estimated to increase treatment cost by 654,502,745 VND per patient, increased 1.295 life years and 2.153 QALYs. Incremental cost-effectiveness ratios were estimated at 505,465,854 VND/LY and 304,045,395 VND/QALY. Conclusions: BV consolidation was not cost-effective compared to 3GDP threshold, however, with an appropriate risk-sharing mechanism, the intervention can be cost-effective, improve patients access to the effective treatment and maintain equity in healthcare.

Brentuximab Vedotin and Pembrolizumab Combination in Patients with Relapsed/Refractory Hodgkin Lymphoma: A Single-Centre Retrospective Analysis.

Simple SummaryThe standard treatment for Hodgkin lymphoma (HL) patients presenting a relapsed/refractory (R/R) disease is salvage chemotherapy followed by autologous stem cell transplantation (ASCT). With commonly used chemotherapy combinations, 25–30% fail to proceed to ASCT, with poor outcomes. The aim of this retrospective study was to evaluate the efficacy of brentuximab vedotin (BV) and pembrolizumab combination as a bridge to ASCT in R/R HL patients. We retrospectively collected data from 10 patients, 8 male and 2 female, with a median age of 30.7 years. The median follow-up time was 16.5 months, while the median number of received cycles of treatment was 4 (2–7). Eight patients proceeded to ASCT (80%) and seven of them to subsequent BV maintenance, with two early disease progression (PD). The BV and pembrolizumab combination is a very effective bridge treatment to ASCT for high-risk R/R HL patients. Classical Hodgkin lymphoma (HL) patients presenting a relapsed/refractory (R/R) disease are currently managed with salvage chemotherapy followed by autologous stem cell transplantation (ASCT). However, almost 25–30% of these patients fail to achieve a complete response (CR) with standard salvage regimens. In this retrospective study, we evaluated the efficacy of a combination of brentuximab vedotin (BV) and pembrolizumab in a series of HL patients presenting with a high-risk, multi-refractory disease. Patients achieving a Deauville score ≤4 proceeded to ASCT consolidation. After ASCT, patients received BV as maintenance for a total of 16 administrations. We collected data from 10 patients with a median age of 30.7 years. At a median follow-up of 16.5 months, we reported a complete metabolic remission (CMR) in eight patients (80%), with seven patients (70%) directly proceeding to ASCT (the other two patients in CMR are still undergoing treatment). BV consolidation was started in six patients and completed by three patients (one ongoing, two interruption). Two patients (20%) presented a progressive disease (PD) and subsequently died, while the others are still in CMR. The BV and pembrolizumab combination is a very effective bridge treatment to ASCT for high-risk R/R HL patients.

Brentuximab Vedotin Plus Cyclophosphamide, Doxorubicin, Etoposide, and Prednisone (CHEP-BV) Followed By BV Consolidation in Patients with CD30-Expressing Peripheral T-Cell Lymphomas

Brentuximab Vedotin Plus Cyclophosphamide, Doxorubicin, Etoposide, and Prednisone (CHEP-BV) Followed By BV Consolidation in Patients with CD30-Expressing Peripheral T-Cell Lymphomas

Autologous Stem Cell Transplant Outcome in Classic Hodgkin Lymphoma Patients in the Era of Post-Transplant Brentuximab Vedotin Consolidation

Introduction:Patients newly diagnosed with classic Hodgkin lymphoma (CHL) have over 80% chance of remission with first-line chemotherapy, such as ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) regime. However, 10-40% of patients relapse eventually and require salvage therapy. High-dose therapy with autologous stem cell transplantation (ASCT) remains the standard of care for patients with relapsed or refractory CHL, offering a cure rate of around 50%. This may be further improved to around 60% with post-transplant consolidation with brentuximab vedotin (BV). Post-SCT BV consolidation has been offered to all patients, regardless of the risk group, in British Columbia since late 2015. We set out to review the ASCT outcome in CHL patients in the recent decade at our institution.Methods:All adult patients who received ASCT for relapsed or refractory CHL between July 2011 and June 2020 were included in this retrospective analysis. Information pertaining to their demographics, disease characteristics, treatment history, transplant details, clinical outcomes and post-relapse therapy was obtained by review of electronic data. The data cut-off date was June 28, 2021. Survival outcomes were censored at the last known clinic visit for patients without relapse or death during follow up. Survival analysis was performed using Kaplan-Meier survival function and log-rank test. Pearson's chi-square test and ANOVA were used for comparison between cohorts. The statistical program used was Stata® version 16.1 (Texas, USA).Results:114 patients underwent ASCT for relapsed/refractory CHL. Bulky disease and extranodal involvement were seen in 11% and 40% respectively at relapse. Looking at the ‘high risk criteria’ as defined in the AETHERA trial: 45/114 (40%) patients had primary refractory CHL, 21/114 (18%) had relapsed within 12 months of completing the front-line chemotherapy and 15/114 (13%) had relapsed beyond one year of completing initial treatment but with an extranodal disease.The most commonly used salvage chemotherapy regime was GDP (gemcitabine, dexamethasone, cisplatin; 111/114; 97%). 10/114 (9%) patients received BV after failing salvage chemotherapy pre-SCT. The median number of lines of therapy pre-SCT was two (range 2-5). 94/108 (98%) had a chemosensitive disease with 35/108 (32%) achieving complete remission. 6/108 (6%) patients had a progressive disease at the time of SCT. For the transplant, all patients had a peripheral blood stem cell source and the conditioning regime was either Carmustine/Etoposide/Cytarabine/Melphalan (76%) or Etoposide/Melphalan (24%).After median follow up of 62.2 months, 50/114 (44%) patients relapsed with median relapse-free survival of 20.2 months (range 0.9 - 113.5) and 16/114 (14%) died. The direct cause of death was lymphoma progression in all but three patients (PJP pneumonia, pulmonary fibrosis, traumatic subdural hematoma).Whereas only 4/51 (8%) patients (2 without relapse) received post-SCT BV consolidation via a compassionate access program between July 2011 and October 2015 (cohort 1), 45/63 (71%) patients (33 in remission) received routine BV consolidation between November 2015 and June 2020 (cohort 2). In cohort 2, 44% had primary refractory CHL compared to 33% in cohort 1 but the number of ‘low risk’ patients was similar at 29% (Table 1). The most common reason for no post-SCT BV consolidation in cohort 2 was patient refusal (7/18; 40%). Other causes included BV pre-SCT, early disease progression and patient comorbidities. Only 9/42 (21%) patients with available data in cohort 2 completed the planned 16 cycles of BV consolidation. The median number of cycles was 10.5 (range 1-16). The most common reasons for early termination of BV consolidation were peripheral neuropathy (22/33; 67%) and disease progression (9/33; 27%). There was no statistically significant difference in PFS or OS demonstrated between the two cohorts (Graphs 1, 2).Conclusion:After median follow up of 5 years, 86% of patients remain alive and 56% are alive in remission. In British Columbia, post-SCT BV consolidation has been widely adopted with over 70% of patients receiving at least one cycle since late 2015. Successful completion of post-SCT BV consolidation is, however, limited by a high rate of treatment-limiting peripheral neuropathy. Relapse-free survival benefit of routine post-SCT BV consolidation is not demonstrated in this single-centre cohort. [Display omitted] DisclosuresWhite: Novartis: Honoraria. Sutherland: Janssen: Consultancy, Research Funding; GSK: Research Funding; Karyopharm: Research Funding; Celgene: Consultancy; Amgen: Consultancy. Sanford: Abbvie: Membership on an entity's Board of Directors or advisory committees; Stellar: Membership on an entity's Board of Directors or advisory committees. Abou Mourad: Amgen: Consultancy; Paladin: Consultancy; Pfizer: Consultancy. Song: Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Takeda: Consultancy, Honoraria; GlaxoSmithKline: Honoraria; Kite, a Gilead Company: Honoraria; Bristol Myers Squibb: Honoraria; Sanofi: Honoraria.

Brentuximab Vedotin As Consolidation Therapy Following Autologous Stem Cell Transplantation in Children and Adolescents with Relapsed/Refractory Hodgkin Lymphoma: A Multi-Center Retrospective Analysis

Background:Although the prognosis for children with Hodgkin lymphoma (HL) is excellent, up to 25% of patients experience relapse and require salvage therapy. Event-free survival (EFS) for patients with relapsed or refractory disease (R/R) who require high-dose therapy with autologous stem cell transplantation (ASCT) is between 31-67% (Daw, 2011), and efforts to improve these outcomes are an area of urgent clinical need. Brentuximab vedotin (BV) is an anti-CD30 antibody-drug conjugate combined with monomethyl auristatin E. The phase III AETHERA study (NCT01100502) was a randomized, placebo-controlled trial that demonstrated consolidation with BV following ASCT for adults with R/R HL improved progression-free survival (PFS) in comparison to placebo (5-year PFS 59% vs. 41%) in patients identified as having a high-risk of post-ASCT progression (Moskowitz, 2015, 2018). However, there is limited data on post-ASCT BV consolidation in pediatric patients. Here, we report a retrospective multi-center study of BV as consolidation post-ASCT in pediatric patients with R/R HL.Patients and Methods:We performed a retrospective analysis of pediatric patients aged ≤ 21 years who received BV as consolidative therapy following ASCT for the treatment of relapsed/refractory HL. Data was collected on disease risk factors (refractory disease or relapse ≤ 12 months after frontline therapy, best response of partial remission or stable disease to salvage therapy, presence of extranodal involvement, presence of B symptoms, and number of systemic treatments pre-ASCT ≥ 2), treatment history, BV-related toxicity, and response to therapy. The primary endpoint was 3-year EFS. Events were defined as relapse, progression of disease, or death from any cause.Results:Seventy patients were identified from 14 academic centers. Eighteen received BV >90 days after ASCT and were excluded due to significant delay in initiation of BV. Of the remaining 52 patients, the median age at diagnosis was 15 years (range 4-21), and the median age at diagnosis of R/R disease was 16 years (range 8-22). Twenty-eight patients (54%) were male, 13 (25%) had B symptoms, 19 (37%) had extranodal disease. Six patients (12%) had primary refractory disease and 24 patients (47%) relapsed <12 months after frontline therapy. The median number of salvage regimens received pre-ASCT was 2 (range 1-7). Forty-two patients (81%) received BV as part of a pre-ASCT salvage regimen, 4 (8%) of whom did not receive BV in the regimen immediately prior to ASCT. Radiation therapy was used pre or post-ASCT in 16 patients (31%). Prior to ASCT, 40 patients (77%) were PET-negative (Deauville 1-3), 11 (21%) were PET-positive (Deauville 4-5), and response in 1 (2%) was unknown.The median time from ASCT to the start of BV consolidation was 52 days (range 30-90 days). The most frequent adverse events were peripheral neuropathy of any grade (sensory 19/52 [37%]; motor (14/52 [27%]), and cytopenias (grade 3 or 4: (25/52 [48%]), including neutropenia (13/52 [25%]), thrombocytopenia (7/52 [14%]), and anemia (5/52 [10%]). Three patients (6%) experienced infusion-related reactions. The median number of BV cycles completed post-ASCT was 12 (range 1-17), and 16 patients (31%) completed the full 16 cycles of BV. The most common reason for premature termination was adverse effects (22/36 [61%]). Additional reasons included: physician plan for shorter duration (4/36 [11%]), patient/family decision (3/36 [8%]), and progression (1/36 [3%]). Treatment was still ongoing in 3 patients and reason for premature termination was not reported for 17/36 patients (47%).With a median follow of 2.8 years (range 0.1 to 6.25 years) the three-year EFS was 92% [95%CI: 83-100]. Patients with 0-1 risk factors (15/52 [29%]) and ≥ 2 risk factors (37/52 [71%]), had a 3-year EFS of 100% and 90% [95%CI: 79-100], respectively. Fifty patients (96%) are alive with no evidence of disease, while 2 (4%) patients are alive with disease. No deaths have occurred.Conclusion:The use of post-ASCT BV consolidation for pediatric patients with R/R HL is associated with a favorable safety and tolerability profile. In this cohort, the combination of salvage therapy, HD-chemotherapy/ASCT, and BV consolidation resulted in extremely promising outcomes and warrants further investigation in a prospective pediatric trial. [Display omitted] DisclosuresLeger: Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbott Diagnostics: Research Funding. Roth: Merck: Consultancy; Janssen: Consultancy.

Brentuximab Vedotin Plus ESHAP (BRESHAP) Versus ESHAP As Salvage Strategy for Patients with Primary Refractory or Relapsed Classical Hodgkin's Lymphoma. Preliminary Results from the Breselibet Prospective Clinical Trial

Brentuximab Vedotin Plus ESHAP (BRESHAP) Versus ESHAP As Salvage Strategy for Patients with Primary Refractory or Relapsed Classical Hodgkin's Lymphoma. Preliminary Results from the Breselibet Prospective Clinical Trial

HL-007: Brentuximab Vedotin Consolidation Therapy after Autologous Stem-Cell Transplantation in Patients with High-Risk Hodgkin Lymphoma: Multi-Center Retrospective Study

Context The AETHERA trial reported an increased progression-free survival (PFS) when brentuximab vedotin (BV) was used as maintenance therapy in high-risk Hodgkin lymphoma (HL) after autologous stem cell transplantation (ASCT). Objective To determine the impact and safety of BV as maintenance after ASCT in real-world patients. Design Patients with relapsed/refractory HL started on BV consolidation therapy after ASCT due to high risk of relapse, between January 2016 and July 2019, from 25 institutions, were retrospectively analyzed. Setting All patients were followed by the bone marrow transplantation team of their hospital. Patients or Other Participants Seventy-five patients were included in the study. The median follow-up time was 26 months. The most common high-risk features were primary refractory or relapsed disease Interventions BV consolidation was initiated within 6 months of ASCT and administered at a dose of 1.8 mg/kg intravenous infusion over 30 min every 3 weeks for up to 16 cycles in an outpatient setting. Main Outcome Features The primary endpoint of the study was PFS; secondary endpoints were safety and overall survival (OS). Results At the time of analysis, 42 patients completed consolidation courses, and BV was discontinued in 33 patients. Fifty patients had an ongoing response (CR in 41, PR in six, and SD in three patients), 25 had progressed. Ten died in the follow-up, eight with progressive disease and two due to infection while in CR. The 2-years PFS and OS rates were 67.75% (95% CI:0.55–0.77) and 87.61% (95% CI:0.76–0.94), respectively. Seventeen patients (23%) received BV in the pre-ASCT treatment lines, and there was no survival difference between the BV naive and BV exposed groups. The most common adverse events were neutropenia (27%) and peripheral neuropathy (21%). Sixteen patients (21.3%) experienced grade 3 or 4 toxicity. BV was discontinued due to AE in 12 patients. Conclusions Consolidation with BV after ASCT can achieve a 2-year PFS of 67.75% (95% CI: 0.55–0.75) with an acceptable toxicity profile.

Brentuximab vedotin consolidation therapy after autologous stem-cell transplantation in patients with high-risk Hodgkin lymphoma: Multicenter retrospective study.

The AETHERA trial reported an increased progression-free survival (PFS) when brentuximab vedotin (BV) was used as maintenance therapy in high-risk Hodgkin lymphoma (HL) after autologous stem cell transplantation (ASCT). Thus, we aimed to determine the impact and safety of BV as maintenance after ASCT in real-world patients. Seventy-five patients with relapsed/refractory HL started on BV consolidation therapy after ASCT due to high risk of relapse, between January 2016 and July 2019, from 25 institutions, were included in the study. The median follow-up time was 26 months. The most common high-risk features were primary refractory or relapsed disease <12 months (n=61), lack of complete response (CR) to the last salvage regimen (n=51), and having had at least two salvage regimens (n=29). At the time of analysis, 42 patients completed consolidation courses, and BV was discontinued in 33 patients. Fifty patients had an ongoing response (CR in 41, PR in 6, and SD in 3 patients), 25 had progressed. Ten died in the follow-up, eight with progressive disease and two due to infection while in CR. The 2-year PFS and OS rates were 67.75% (95% confidence interval [CI]: 0.55-0.77) and 87.61% (95% CI: 0.76-0.94), respectively. Seventeen patients (23%) received BV in the pre-ASCT treatment lines, and there was no survival difference between the BV-naïve and BV-exposed groups. The most common adverse events were neutropenia (27%) and peripheral neuropathy (21%). Sixteen patients (21.3%) experienced grade 3 or 4 toxicity. BV was discontinued due to adverse event in 12 patients. Consolidation with BV after ASCT can achieve a 2-year PFS of 67.75% (95% CI: 0.55-0.75) with an acceptable toxicity profile.

ABVD followed by BV consolidation in risk-stratified patients with limited-stage Hodgkin lymphoma

AbstractApproximately 90% of limited-stage Hodgkin lymphoma (HL) patients are projected to be cured with standard therapy, but many do not live their expected life span because of late treatment–related complications. New treatment paradigms are needed to reduce the use of radiation therapy (RT) as well as conventional chemotherapy drugs while improving upon current standard-of-care survival outcomes. In this phase 2 multicenter study, patients with non-bulky limited-stage HL received doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by brentuximab vedotin (BV) consolidation. Forty-one patients were enrolled, and patient characteristics included median age of 29 years (range, 19 to 67 years), 58% were female, 45% had unfavorable disease, and 98% had stage II disease. Based on positron emission tomography (PET)–based risk stratification, patients received 2 to 6 cycles of ABVD followed by 6 cycles of BV. After ABVD followed by BV, 95% of evaluable patients (37 out of 39; 95% confidence interval [CI], 83%-99%) achieved PET-negative status. In the intent-to-treat patient population, the estimated 3-year progression-free survival (PFS) rate was 92%, and the overall survival (OS) rate was 97%, with a median follow-up of 47 months. All 37 patients who achieved negative PET status after BV consolidation effectively avoided RT and remain in remission with estimated 3-year PFS and OS rates of 100%. In conclusion, BV demonstrates encouraging clinical activity when it follows ABVD therapy in limited-stage HL. Early incorporation of BV may reduce the use of RT as well as conventional chemotherapy drugs while achieving favorable survival outcomes in risk-stratified patients with non-bulky limited-stage HL. This trial was registered at www.clinicaltrials.gov as #NCT01578967.

Optimizing outcomes in relapsed/refractory Hodgkin lymphoma: a review of current and forthcoming therapeutic strategies.

The outcome of patients with relapsed/refractory classical Hodgkin lymphoma (rr-cHL) has improved considerably in recent years owing to the approval of highly active novel agents such as brentuximab vedotin and Programmed Death-1 (PD-1) inhibitors. Although no randomized trials have been conducted to provide formal proof, it is almost undisputable that the survival of these patients has been prolonged. As autologous stem-cell transplantation (SCT) remains the standard of care for second-line therapy of most patients with rr-cHL, optimization of second-line regimens with the use of brentuximab vedotin, or, in the future, checkpoint inhibitors, is promising to increase both the eligibility rate for transplant and the final outcome. The need for subsequent therapy, and especially allogeneic SCT, can be reduced with brentuximab vedotin consolidation for 1 year, while pembrolizumab is also being tested in this setting. Several other drug categories appear to be active in rr-cHL, but their development has been delayed by the appearance of brentuximab vedotin, nivolumab and pembrolizumab, which have dominated the field of rr-cHL treatment in the last 5 years. Combinations of active drugs in chemo-free approaches may further increase efficacy and hopefully reduce toxicity in rr-cHL, but are still under development.

Brentuximab Vedotin As Consolidation Therapy Post Hematopoietic Stem Cell Transplantation for Patients with Relapsed or Refractory Hodgkin Lymphoma: A Real World Analysis of the Colombian Experience

Introduction: High-dose chemotherapy followed by autologous stem-cell transplantation (auto-HCT) is standard of care for patients with relapsed or primary refractory classical Hodgkin lymphoma (cHL). Brentuximab vedotin (BV) consolidation after auto-HCT improves progression-free survival of cHL patients with primary refractory disease and high risk for relapse as seen in the AETHERA trial. There are no published reports of BV consolidation post auto-HCT in cHL patients treated in developing countries. The aim of this study is to determine the clinical outcomes and safety of BV consolidation after auto-HSCT in a cohort of Colombian patients with relapsed or refractory (R/R) cHL. Methods: A retrospective cohort study was conducted at ten tertiary referral centers in five cities in Colombia. Data from patients with R/R cHL who underwent auto-HCT followed by BV consolidation was collected and analyzed. Descriptive statistics were used to analyze patient's demographic characteristics. The Kaplan-Meier method was used to assess overall survival (OS) and progression-free survival (PFS) rates and log-rank test was used to compare survival between groups. All data were analyzed by R Studio software. Results: Fifty-three patients with a confirmed diagnosis of cHL were included, 49,1% were women. Median of age at auto-HCT was 29 years (range 17 - 66). The most frequently used frontline regimen was ABVD 90,6%. Median number of treatment lines including auto-HCT was 3 (range 2 to 7). 83% of patients had BV consolidation after 1stAUtoHCT and 17% after 2 auto-HCT. The most common high-risk feature before auto-HCT was primary refractory cHL (54,7%). Responses were determined by Lugano criteria. However, unconfirmed complete responses (uCR) per 2007 IWC criteria were used due to lack of PET-CT availability of evaluation in some centers, where CT scan were used. The overall rate (ORR) before auto-HCT was 94,4% with complete response (CR) in 28,3%, uCR 20,8% and partial response (PR) in 45,3% of patients. The ORR after auto-HCT was 90,5% with CR in 52,8%, uCR in 22,6%, and PR 15,1%. Table1. A total of 531 BV cycles were administered as post auto-HCT consolidation with a median of 11 cycles (range 1-16). A median of 23 days between each cycle was documented (range 7-210 days). The most common grade 3-4 toxicities were peripheral neuropathy (18,8%), fatigue (9,4%), weight loss (5,6%). OS at 132 months was 92,5% (CI95%: 4,9 - NR) (Figure A), and the median PFS was not reached (CI 95%: 36.5 months - Not reached) with 75,5% PFS at 132 months, with a mean of follow-up of 23,5 months (Range: 4,2 - 133,2 months) (Figure B). There was a trend towards worse PFS in patients treated with ≥ 3 regimens before auto-HCT Median: 38.7 months, (CI 95%: 36.5 - NA) Vs. 2 lines: Median: NR (CI 95%: 4,2-NR) P= 0.4.(Figure C). Also patients that required a second transplant followed by BV consolidation had a worse PFS, compared to the ones that underwent BV consolidation post first auto-HCT: median: 13.6 months (CI 95%: 6.7- NR)Vs. median: NR (CI95%: 38,7 - NR) respectively p=0,009 (Figure D). Twelve patients relapsed and 4 patients died form disease progression. Conclusions: BV consolidation after auto-HCT in high-risk R/R cHL patients treated in a developing country setting seems to be a safe and effective treatment. Although OS and PFS were slightly superior to the ones reported in the AETHERA trial, the mean of follow-up in our analysis is shorter. Another shortcoming of our analysis are the inherit limitation of a retrospective cohort. These retrospective results need to be assessed in prospective trials that specifically includes Latin-American with high-risk patients with R/R cHL. Disclosures Patiño: Amgen: Speakers Bureau. Enciso-Olivera:Takeda: Speakers Bureau. Otero-de la Hoz:Takeda: Speakers Bureau. Martínez Cordero:Takeda: Speakers Bureau. Karduss:Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Abello:Takeda: Other: Participation in advisory board meeting. Sandoval-Sus:Seattle Genetics: Membership on an entity's Board of Directors or advisory committees.

Preliminary Results from a Phase 2 Trial of Brentuximab Vedotin Plus Cyclophosphamide, Doxorubicin, Etoposide, and Prednisone (CHEP-BV) Followed By BV Consolidation in Patients with CD30-Positive Peripheral T-Cell Lymphomas

Preliminary Results from a Phase 2 Trial of Brentuximab Vedotin Plus Cyclophosphamide, Doxorubicin, Etoposide, and Prednisone (CHEP-BV) Followed By BV Consolidation in Patients with CD30-Positive Peripheral T-Cell Lymphomas

PB2342 SAFETY AND EFFICACY OF 4 CYCLES OF BRENTUXIMAB VEDOTIN AS CONSOLIDATION AFTER AUTOLOGOUS PERIPHERAL STEM CELL TRANSPLANTION IN RELAPSED/REFRACTORY HODGKIN'S LYMPHOMA

Background: Brentuximab Vedotin (BV) is a chimeric anti CD30 IgG1 antibody, conjugated to synthetic antitubulin momomethyl auristatin. BV is approved for the treatment of classical Hodgkin lymphoma (HL) in relapse either after autologous stem cell transplantation (ASCT) or after two lines of combination chemotherapy in transplant ineligible patients. The AETHERA trial revealed increased PFS when BV is used as maintenance therapy for 16 cycles in high risk patients after ASCT. However, this schedule is associated with a high cost and significant toxicity particularly in term of peripheral neuropathy. Aims: Our primary objective is to assess the efficacy of 4 cycles Brentuximab as consolidation therapy after ASCT for relapsed/refractory (R/R) HL. Secondary objectives include side effects, progression free survival (PFS), and overall Survival (OS). Methods: Patients and Methods: This is a retrospective single center analysis approved by the IRB of the American University of Beirut Medical Center. We included in this study consecutive patients with R/R HL who underwent ASCT between 2014 and 2017, and received BV consolidation post-ASCT. Results: We identified 18 consecutive adult patients with R/R HL treated with BV 1.8 mg/kg IV every 4 weeks as consolidation therapy after ASCT. The indications for BV consolidation was primary refractory disease in 9 patients (50%), early relapse in 8 patients (44%) (after a median time of 10 months; range, 3-11) and extranodal involvement in one patient (6%). The median number of lines of therapy pre-ASCT was 3 (range, 2-5). The median time to BV initiation post-ASCT was 68 days (range, 35-188). Patients received a median of 4 cycles (range, 1-5) of BV post-ASCT. After a median follow up of 32 months (range, 20-53), three (17%) patients relapsed after ASCT. The median time to relapse was 6 months (range, 4-8). Median PFS and OS were not reached. We did not observe any significant toxicities during or after therapy. Summary/Conclusion: Conclusion: 4 cycles of BV consolidation after ASCT seem to be safe and effective in preventing relapse, however our findings need to be confirmed with larger prospective studies.

Brentuximab Vedotin Infusion Reaction Management: A Case Study

We report a case of a grade 3 (Common Terminology Criteria for Adverse Events [CTCAE]) infusion reaction to brentuximab vedotin (Adcetris), in a patient with refractory Hodgkin lymphoma, at a large National Cancer Institute-designated cancer center in the Midwest (National Cancer Institute, 2010). Acute infusion reaction management and subsequent premedication strategies are outlined. Ms. R is a 30-year-old woman who presented with stage IV Hodgkin lymphoma at the age of 29. Initial staging revealed lymphadenopathy above and below the diaphragm, as well as fluorodeoxyglucose (FDG)-avid lung lesions, splenic lesions, and multiple sites of bony involvement. Bone marrow biopsy was negative. She was treated with six cycles of chemotherapy with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), to which she obtained a complete response by positron emission tomography-computed tomography (PET-CT) criteria. Ten months after chemotherapy completion, she presented with new PET-avid adenopathy in the cervical and paratracheal regions, and a biopsy revealed recurrent Hodgkin lymphoma. Salvage chemotherapy was administered with ifosfamide carboplatin, and etoposide (ICE). After two cycles of salvage chemotherapy, a PET-CT confirmed a complete response, and she proceeded to an autologous stem cell transplant with a preparative regimen of carmustine, etoposide, cytosine arabinoside, and melphalan (BEAM). Brentuximab vedotin consolidation therapy was prescribed in the post-transplant consolidation setting, beginning 45 days after stem cell reinfusion, given the patient's high risk for recurrence. This strategy was based upon the results of the AETHERA phase III clinical trial (Moskowitz et al., 2015), showing improvement in progression-free survival with brentuximab vedotin consolidation therapy, post autologous transplant. The first dose of brentuximab vedotin was administered without difficulty, at full dose (1.8 mg/kg) at a standard infusion time of 30 minutes. The second dose of brentuximab vedotin was complicated by nausea, chest pain, and dysphagia within 10 minutes of medication initiation. Upon the emergence of these symptoms, the brentuximab vedotin infusion was held. Vital signs were stable, with a temperature of 36.9˚C, pulse 84, respirations of 20, and blood pressure of 107/67 mm Hg. Oxygen saturations were 99% on room air. Diphenhydramine (50 mg) was administered intravenously (IV), along with 20 mg of IV famotidine. An electrocardiogram (ECG) was obtained, which was unremarkable, showing normal sinus rhythm. Fifteen minutes later, the symptoms of chest pain and shortness of breath persisted, so hydrocortisone at 100 mg IV was administered, with an additional 25 mg of IV diphenhydramine and 20 mg of IV famotidine. Intraveous granisetron was given for nausea. Thirty minutes after onset, the chest pain was persistent, and oxygen saturations were normal. Hydrocortisone (50 mg) was administered intravenously, and Ms. R's condition improved, with resolution of her symptoms within 30 minutes of the second hydrocortisone dose. The brentuximab vedotin was restarted 30 minutes after symptom resolution at a decreased infusion rate to be administered over 60 minutes. Thirty minutes later, however, Ms. R developed tingling and numbness in her feet and tongue. The brentuximab vedotin infusion was again held, and 100 mg of IV methylprednisolone was administered. Ms. R's symptoms resolved within 40 minutes, and the brentuximab vedotin infusion was able to be continued over a prolonged period of more than 4 hours. Vital signs were checked every 15 minutes during the infusion reaction and remained stable throughout. The infusion was discontinued with 40 mg of drug remaining, due to the prolonged infusion time. Given the clear benefits of brentuximab consolidation in improving progression-free survival post transplant (Moskowitz et al., 2015) in high-risk Hodgkin lymphoma, it was thought the benefit of brentuximab vedotin consolidation outweighed the possible risks of subsequent infusions. Upon reviewing the available literature regarding brentuximab vedotin hypersensitivity reactions, which will be outlined in the discussion summary, we instituted the premedication strategy for subsequent infusions outlined in the Table on p 628. Standard epinephrine and methylprednisolone were available at the bedside in the event of any anaphylactic reaction. This regimen was chosen based on the clinical rationale for H1 and H2 blockade, as well as corticosteroid and antipyretic coverage, in the prevention of hypersensitivity reactions, not classified as anaphylaxis. With the institution of the outlined premedications, Ms. R tolerated subsequent infusions well, at full dose and at standard infusion rates, with no documented infusion reactions, and was able to complete a total of 16 cycles of consolidation therapy.