Safety Of Brentuximab Vedotin Research Articles

Phase 2 trial of brentuximab vedotin (BV) with pembrolizumab (pembro) in patients with previously treated metastatic non-small cell lung cancer (NSCLC) or cutaneous melanoma (SGN35-033): Overall survival.

2617 Background: BV, a CD30 directed antibody-drug conjugate, may selectively deplete a subset of regulatory T-cells (Tregs) that express CD30 and re-sensitize tumors to anti-PD-1 therapy. This ongoing, multi-cohort, multicenter, open-label trial evaluating the efficacy and safety of BV+pembro in patients (pts) with anti-PD-1 refractory solid tumors previously reported an ORR (8-22%), DCR (67-80%), and CD8+T cell infiltration in on-treatment biopsies of responders (Lee, SITC 2023). Here we report OS and biomarker analyses. Methods: Pts with primary refractory (progression without response or SD for < 6 months) or secondary refractory (progression after response for ≥3 months or SD for ≥6 months) NSCLC or melanoma who progressed on anti-PD-1 therapy were included. Pts received BV (1.8 mg/kg) and pembro (200 mg) every 21 days. The primary endpoint was confirmed ORR. Exploratory endpoints included OS and biomarker analyses of blood and tumor samples. Results: 55 pts with NSCLC and 58 pts with melanoma were dosed (86% white, 63% male; 57% ≥ age 65 yrs). Pts received 3 median prior lines of therapy (as previously reported). Investigator-assessed response was measured according to RECIST v1.1. At a median follow up of 17.2 months, median OS (mOS) was 13.9 months (NSCLC) and 12.9 months (melanoma) (Table 1). The estimated probability of survival (Kaplan-Meier) at 12 months was 54.0% (95% CI 43.69, 63.22) for the study population. Immune mediated AEs were reported in 25% of pts, Grade ≥3 TEAEs in 56%, TESAEs in 42%, and TE peripheral neuropathy (SMQ) in 48% of pts. 17% of pts discontinued treatment due to TEAEs. No new safety signals were identified and no deaths due to treatment-related AEs were reported. Paired tumor biopsies from 19 pts showed increased CD8+T cell infiltration in 11 pts. Conclusions: These data support the immunomodulatory capacity of BV with pembro. This combination shows encouraging OS data in pts with solid tumors who have progressed on anti-PD-1 therapy. The safety profile is comparable to previously reported data. The study remains ongoing. Clinical trial information: NCT04609566 . [Table: see text]

Brentuximab vedotin for skin involvement in refractory diffuse cutaneous systemic sclerosis, an open-label trial.

We explored the efficacy and safety of brentuximab vedotin, a chimeric anti-CD30 antibody drug conjugate, in patients with severe active diffuse cutaneous systemic sclerosis (dcSSc). This phase II proof-of-concept, single center, open-label, single arm, investigator-initiated trial included patients ≥18 years, with dcSSc, modified Rodnan skin score (mRSS) ≥15 with <5 years since the first non-Raynaud's symptom and/or skin worsening despite immunosuppression who were treated with intravenous brentuximab vedotin 0.6 mg/Kg q3 weeks for 45 weeks. The primary end point was a decrease in mRSS of ≥ 8 points at 48 weeks. Eleven patients were treated with brentuximab vedotin, with 9 completing the study. The mean mRSS reduction at week 48 was 11.3 (95% CI 6.9, 15.8; p= 0.001), meeting the primary end point in the intention to treat analysis (7/11 had a decrease in mRSS ≥8). The % forced vital capacity increased by 7.8% (12.5). The Composite Response Index in dcSSc (CRISS) suggested a beneficial treatment effect (86% ≥0.6). Most adverse events were mild. No SAEs were attributed to brentuximab vedotin. In dcSSc, brentuximab vedotin improved skin and FVC; without safety concerns. A placebo-controlled trial is warranted to corroborate these initial findings.

A multi-center and non-interventional registry of brentuximab vedotin in patients with relapsed or refractory CD30-positive lymphoma: the CISL1803/BRAVO study.

Brentuximab vedotin (BV), a potent antibody-drug conjugate, targets the CD30 antigen. In Korea, BV has been approved for the treatment of relapsed or refractory Hodgkin lymphoma (HL), anaplastic large-cell lymphoma (ALCL), and cutaneous T-cell lymphomas, including mycosis fungoides (MF). However, there are limited data reflecting real-world experiences with BV treatment for HL, ALCL, and MF. This was a multicenter, non-interventional registry study of the efficacy and safety of BV in patients with relapsed or refractory CD30-positive lymphoma (CISL1803/BRAVO). Outcomes were determined based on the occurrence of relapse or progression and overall survival after BV treatment. A total of 85 patients were enrolled in this study. The median number of BV cycles was 10 (range, 2‒16) in the patients with HL. The objective response rate (ORR) of patients with HL to BV was 85.4% (41/48), comprising 27 complete responses (CRs) and 14 partial responses (PRs). The ORR of ALCL was 88% (22/25), consisting of 17 CRs and five PRs, whereas the ORR of MF was 92% (11/12). At the median follow-up of 44.6 months after BV treatment, the median post-BV progression-free survival of HL, ALCL, and MF patients was 23.6 months, 29.0 months, and 16.7 months, respectively (P=0.641). The most common side effect of BV was peripheral neuropathy; 22 patients (25.9%, 22/85) experienced peripheral neuropathy (all grades). The treatment outcomes of patients with relapsed or refractory CD30-positive lymphoma improved with BV treatment, and the safety profile was manageable.

Efficacy and Safety of Modified BV-AVD-R Regimen in Chinese Children with Previously Untreated Intermediate- and High-Risk Classical Hodgkin's Lymphoma: An Open Label, Non-Randomized, Single-Arm, Phase 2 Study from Single Center

Introduction Classical Hodgkin lymphoma (cHL) accounts for about 4.8% of childhood malignant neoplasm, and the incidence of cHL in Chinese children and adolescents (0-19 years old) is about 1.78/million, which is a group of relatively low malignancy and curable tumor. With the prolonged survival of children and adolescents with cHL, the incidence of muscle and skeletal malformations, lung and cardiovascular diseases, infertility and secondary tumors increased significantly during long-term follow-up. Therefore, the goal of childhood cHL treatment is to achieve and maintain the high efficacy while reduce the treatment-related complications. Brentuximab vedotin (BV), an antibody-drug conjugates (ADC) targeting CD30, has been evaluated well in American children and some regions, but no clinical studies to explore the efficacy and safety of BV in Chinese children with cHL. Therefore, the objective of our study is to evaluate the efficacy (objective response rate, including CR and PR) and safety (short - and long-term safety) of modified BV-AVD-R regimen (Brentuximab vedotin + Rituximab + Doxorubicin + Vinblastine + Dacarbazine) in Chinese children with previously untreated intermediate- and high-risk classical HL. Methods This study is a prospective study with period from October 2022 to December 2024, and planned to enroll 44 children with newly diagnosed intermediate- and high-risk classical HL. All patients will undergo PET/CT at the time of initial diagnosis and after 2 cycles of modified BV+R+AVD regimen to determine early response. Rapid early responders (RER) defined as CR after 2 cycles of therapy. Slow early responders (SER) defined as no CR (partial response (PR) or stable disease) after 2 cycles of therapy. Intermediate-risk patients were stage IA bulk/E, IB, IIA bulk/E, IIB, and IIIA. High-risk patients were stage IIB bulk/E, IIIA bulk/E, IIIB, and IVA/B(Figure 1). The primary endpoints include ORR (CR+PR) and adverse events. The secondary endpoints include progression-free survival (PFS), event-free survival (EFS) and overall survival (OS) at 6 months and 1 year. Results From October 2022 to July 2023, a total of 14 children with newly diagnosed classical HL were enrolled, and 12 patients who had completed at least 2 cycles treatment were eligible for evaluation. 9 boys and 3 girls were enrolled, with median age of 10 years (range 7-15 years). Risk group: 9 patients in high-risk group, 3 patients in intermediate-risk group; Clinical stage: 5 patients in stage IIIA, 2 patients in stage IIIB, 4 patients in stage IVA, and 1 patient in stage IVB. Pathologic subtype: 7 patients of nodular sclerosis type and 5 patients of mixed cell type. Treatment: A total of 33 cycles of modified BV+R+AVD regimen were completed, with 66 doses of BV. The median number of treatment cycles was 3 cycles (range 2-6). 11 patients achieved CR and 1 patient achieved PR after 2 cycles, and the ORR was 100% (12/12). As of July 28, 2023, 4 children had stopped follow-up and achieved CR without sequential radiotherapy. The median follow-up was 6 months (range 2-10). 12 patients successfully received and completed BV infusions, mild nausea and vomiting (10/12), alopecia (9/12) and sensory abnormalities (3/12) were observed. Serious adverse events were mainly grade ≥3 blood cell abnormalities (10/12), none of which had an impact on the treatment flow. No patient withdrew from the study, indicating good adherence to the regimen. Conclusion The risk-adapted modified BV+R+AVD regimen for newly diagnosed Chinese children and adolescents with classical HL showed favorable treatment outcomes with good early response rate and sustained response rate. The regimen could also reduce sequential radiotherapy and demonstrated well safety and tolerability. The study is still ongoing.

A Spanish Medical Record Review of Adults with Relapsed or Refractory CD30+ Malignancies When Re-Treated with Brentuximab Vedotin (BV): Preliminary Analysis of the Believe Study (NCT:04998331)

Background: The efficacy and clinical benefit of BV in patients with CD30+ relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL), cutaneous T cell lymphoma (CTCL) [mycosis fungoides (MF) or primary cutaneous anaplastic large cell lymphoma (pcALCL)] and systemic anaplastic large cell lymphoma (sALCL) have been shown in Ph2-3 pivotal studies (NCT00848926, NCT01578499, NCT00866047). However, the evidence of BV use as a retreatment option is scarce. There are only two studies with available data on the effectiveness and safety of brentuximab vedotin (BV) in the retreatment setting. This research aims to investigate the effectiveness and safety of retreating these populations with BV in the real-world setting in Spain. Methods: Non-interventional, retrospective, multicenter, medical chart review study conducted in 30 public and private Spanish sites. The study included patients aged ≥18, with confirmed diagnosis of cHL, CTCL (MF and pcALCL) and sALCL, CD30 positive, previously treated with BV as monotherapy or as a combination with another antitumor agent, with evidence of objective response and subsequent disease progression, who received ≥2 doses of BV as retreatment and a minimum of ≥6 months of follow-up, discontinuation due to toxicity, or until death. Results: Of the 51 patients enrolled, 43 were eligible for this preliminary analysis (Table 1): 16 with cHL, 12 with MF, 2 pcALCL and 13 with sALCL. The median age of the total population was 47 (33.5-51.5) years, and 58% were women. At retreatment, the Eastern Cooperative Oncology Group performance status (ECOG PS) of the patients was poorer: 18 (52.9%) had ECOG PS of 0; 13 (38.2%) had ECOG PS of 1, 2 (5.9%) had ECOG PS of 2, and 1 (2.9%) had ECOG PS of 3, and 40 patients (93%) presented with comorbidities (Table 1). The median time from the first treatment with BV to the retreatment initiation was 18 (7-108) months, with at least one treatment before BV retreatment in most of the patients (n=40; 93%) (Table 1). At initiation of the retreatment period, more than 50% of patients presented advance clinical stage (III and IV). 27 patients (67.5%) discontinued/terminated retreatment with BV after a median of 5.5 (3.5-7) cycles. The median time from end of BV retreatment until last available follow-up was 8 (6-12) months and 73% of patients were alive. 10 patients were exitus and 43.6% presented with adverse events, mainly peripheral sensory neuropathy (24.2%) (Table 1). Conclusion: This chart review is the first Spanish study to collect information on BV retreatment in patients with CD30+ malignancies, providing information of clinical characteristics and treatment patterns in real-word practice. As BV may become established as a preferred first-line therapeutic option for both untreated stage IV in cHL and sALCL, future research efforts could be aimed at further exploring the efficacy and safety of BV retreatment in patients who progress or relapse after receiving frontline BV treatment. Further analysis of this study will be provided at the congress to determine efficacy and safety results associated to BV retreatment in the Spanish population at clinical practice. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Brentuximab vedotin in the treatment of cutaneous T-cell lymphomas: Data from the Spanish Primary Cutaneous Lymphoma Registry.

Brentuximab vedotin (BV) has been approved for CD30-expressing cutaneous T-cell lymphoma (CTCL) after at least one previous systemic treatment. However, real clinical practice is still limited. To evaluate the response and tolerance of BV in a cohort of patients with CTCL. We analysed CTCL patients treated with BV from the Spanish Primary Cutaneous Lymphoma Registry (RELCP). Sixty-seven patients were included. There were 26 females and the mean age at diagnosis was 59 years. Forty-eight were mycosis fungoides (MF), 7 Sézary syndrome (SS) and 12 CD30+ lymphoproliferative disorders (CD30 LPD). Mean follow-up was 18 months. Thirty patients (45%) showed at least 10% of CD30+ cells among the total lymphocytic infiltrate. The median number of BV infusions received was 7. The overall response rate (ORR) was 67% (63% in MF, 71% in SS and 84% in CD30 LPD). Ten of 14 patients with folliculotropic MF (FMF) achieved complete or partial response (ORR 71%). The median time to response was 2.8months. During follow-up, 36 cases (54%) experienced cutaneous relapse or progression. The median progression free survival (PFS) was 10.3months. The most frequent adverse event was peripheral neuropathy (PN) (57%), in most patients (85%), grades 1 or 2. These results confirm the efficacy and safety of BV in patients with advanced-stage MF, and CD30 LPD. In addition, patients with FMF and SS also showed a favourable response. Our data suggest that BV retreatment is effective in a proportion of cases.

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.

The Management of Relapsed Hodgkin´s Lymphoma after Haploidentical Stem Cell Transplantation: Donnor Lymphocyte Infusion and Brentuximab Vedotin

IntroductionDespite the high cure rate of Hodgkin lymphoma (HL) with conventional radiochemotherapy, HL is refractory in 15% to 30% of patients. In those patient who relapse or refractory to chemotherapy Allogeneic transplantation (alloSCT) will be an option, despite the promising results the rate of relapse is higher. In this situation there is not standardized treatment, we hypothesized that treatment with Brentuximab Vedotin (BV) in combination with donor lymphocyte infusion (DLI) would be a promising approach for relapsed HL after alloSCT that selectively targets lymphoma cells and enhances the graft versus leukemia (GvL) response by the induction of immunogenic cell death.Material and methodBetween 2014-2016 we studied 6 patients who were relapses of HL after haploSCT, we designed a treatment algorithm combining BV infusions during 6 cycles (1.8 mg/kg per day every 21 days) with donor DLI)administration in escalate dosis 1x10e4/kg CD3, increasing 1 log for dosis in an alternating regimen after the third cycles of BV. We stop the DLI when GVHD appear or toxicity, we perform a PET-CT after the first 3 cycles BV, after ILD + 6 cycles BV and 3 month after finish the treatment designed. We analisis safety, complication an side effect of the combination. The aim of this study was to retrospectively evaluate the efficacy and safety of BV + DLI in HL relapsing or progressing after allo-SCT.ResultsA total of 4 patients (66%) were nodular sclerosis histological subtype and 34% (2 patients) was linfocitic predominance. The median age was 32 years (22-48). Median follow-up was 837 days (405-975). The median of treatment lines received before transplantation was 6 (4-7). Only 2 patients (34%) had reached haploTPH in complete remission.Peripheral blood was used as progenitors source in 66% (6). The median time to relapse was 286 days (range 180-463). 5 patients (83%) received BV before alloSCT, only 2 (34%) achieved CR.All the patients relapse after the alloSCT, then we decide began the designed treatment, after the first 3 cycles of BV, 17% (1 patients) was in CR. After that we associated DLI in all the cases, the median was 8 (3-13) plus another 3 cycles of BV, after this in the reevaluation CR was observed in 50% (3 patients). When combined radiotherapy (RT) in selected cases, CR rate was 100% in the PET-CT 3 month after finish the treatment designed. The combination DLI + BV was without important toxicity. Acute GVHD was observed in 83% (5 patients) the 100% was grade I-II. 66% (4 patients) developed chronic GVHD, 100% was limited extension. Treatment with BV + DLI resulted in an PFS of 100%.ConclusionsThe combination treatment was well tolerated, confirming a manageable safety profile for BV plus DLI after alloSCT, is an effective and safe therapy to achieve disease control in HL relapsing after alloSCT. We assumed that the combination of BV with DLI will have the potential to further increase the GvL effect. Despite this findings, we need multicentric studies to perform standarized treatments. DisclosuresNo relevant conflicts of interest to declare.

OP0172 BRENTUXIMAB VEDONTIN FOR SKIN INVOLVEMENT IN REFRACTORY DIFFUSE CUTANEOUS SYSTEMIC SCLEROSIS, INTERIM RESULTS OF A PHASE IIB OPEN-LABEL TRIAL

Background:Systemic sclerosis (SSc) is an autoimmune disease affecting multiple organs causing morbidity and mortality. Treatments targeting SSc skin often have limited success. The presence of CD30+ lymphocytes in skin biopsies and increased levels of serum CD30 have been reported in SSc patients1. This could constitute a new therapeutic target.Objectives:To explore the efficacy and safety of brentuximab vedotin, a chimeric anti-CD30 antibody drug conjugate, in patients with severe active diffuse cutaneous SSc who failed multiple treatments.Methods:This Phase IIb, single center, open-label, investigator-initiated trial will recruit 10 patients. Brentuximab vedotin 0.6 mg/Kg was infused intravenously every 3 weeks for 48 weeks. Inclusion criteria were age ≥18 years, meeting the 2013 ACR/EULAR SSc classification criteria, modified Rodnan skin score (mRSS) ≥15 with &lt;5 years since the first non-Raynaud’s symptom and/or skin worsening despite immunosuppression. Patients were allowed to continue their standard of care medications for SSc except for rituximab. Patients with severe cardiac or pulmonary SSc involvement, severe infections, significant peripheral neuropathy, or active malignancy were excluded. The primary objective was a decrease in mRSS of ≥8 at 48 weeks. The main secondary endpoint was MRSS at 24 weeks. Differences were assessed by paired t tests. Data were compared to 16 age, disease duration, mRSS and past/present use of immunosuppressors-matched controls (ratio 2-3:1) from the Canadian Scleroderma Research Group (CSRG) registry.Results:Eight of 10 patients have been recruited to date; two are in the first 8 weeks and one was withdrawn at her request after developing influenza at week 12. Five subjects (60% female) have reached week 24, and 3 have completed 48 weeks. The mRSS is shown in Table 1. The ΔMRSS for patients treated with brentuximab between weeks 0 and 24 was 8.2 ([CI 95% 2.8, 13.6], p = 0.013) and from 0 to 48 was 15.3 ([CI 95% 8.2, 22.5], p = 0.012). Whereas, the ΔMRSS for the CSRG controls was 3.1 ([CI 95% -2, 8.2], p = 0.211) at 48 weeks. Assuming that mRSS would at least be the same from week 24 to 48 in the 2 cases who are between 24 and 48 weeks with brentuximab, we compared the 5 cases vs controls (Figure 1). ΔMRSS for Brentuximab was 12.2 ([CI 95% 5.9, 18.5], p = 0.006. No cases have developed a peripheral neuropathy and only one SAE (influenza).Table 1.N (SD)NAgeDisease durationmRSS week 0mRSS week 24mRSS week 48mRSS week 48**Case560.2 (9.3)4.5 (2.1)33 (5.2)24.8 (6)15.7 (3)20.8 (8.3)Control1658.5 (8.3)4.9 (2.1)31.3 (5.9)N/D28.1 (7.5)28.1 (7.5)p0.7310.7750.559N/D0.0130.079mRSS = modified Rodnan skin score, N/D = no data, ** = comparisons including 5 cases, assuming stability in MRSS from week 24 to 48 in cases 5 and 6Figure 1.Conclusion:Brentuximab vedontin already achieved the primary endpoint at 24 weeks, after half of the intended recruitment sample reached this landmark. A comparison with CSRG controls showed that mRSS only decreased significantly in patients treated with brentuximab. This interim report suggests that brentuximab vedontin might effectively improve skin involvement in patients with diffuse SSc and severe skin involvement.

Combination of brentuximab-vedotin with skin-directed therapies extends the time to the next therapeutic line in patients with cutaneous T-cell lymphoma.

Brentuximab vedotin (BV) is a potent therapeutic option for CD30-positive cutaneous T-cell lymphoma. Unlike existing studies, BV and other therapeutic procedures were frequently combined for our patients. In this context, the study aims to analyze the effectiveness and safety of BV in a real-world setting. This is a retrospective monocentric study analyzing treatment outcomes for patients with CD30-positive cutaneous T-cell lymphoma treated with BV. 26 patients (median age: 67 years) were included in the study. Patients were treated with 1.8 or 1.2mg/kg b.w. Complete remission (CR) was reached in 30.8% of the patients, and the objective response rate (ORR) was 84.6%. Side effects were seen in 19 of the 26 patients. As a reaction to progressive disease (PD) under BV monotherapy, we included skin-directed procedures such as tumor excision, local radiotherapy, and PUVA for six patients. We re-stabilized the disease and maintained the line of therapy without additional toxicities for a median of seven months longer using this concept. Addition of skin-directed therapies (SDT) after disease progression under BV monotherapy could stabilize the disease's continuous advancement or even lead to partial response, thereby extending the time until the next therapeutic escalation.

A Phase II Study of Brentuximab Vedotin in Patients with Relapsed or Refractory Epstein-Barr Virus-Positive- and CD30-Positive Lymphomas

Background: CD30 is frequently expressed in Epstein-Barr virus (EBV)-infected lymphoid cells and overexpressed in EBV-positive lymphomas. This open-labeled, multi-center, and investigator-initiated phase-II study evaluated the efficacy and safety of brentuximab vedotin in patients with relapsed or refractory EBV-positive and CD30-positive lymphomas (NCT02388490). Methods: Twenty-five patients with relapsed or refractory EBV-positive lymphomas having CD30-positivity (≥ 1% of tumor cells) were administered with 1.8 mg/kg brentuximab vedotin intravenously every 3 weeks up to 16 cycles until disease progression. The primary endpoint was objective response rate and toxicities, duration of response (DoR), progression-free survival (PFS), and overall survival (OS) were the secondary endpoints. Findings: Twenty-two patients (88%), median age of 65 years, were EBV-positive mature T/NK cell neoplasms (angioimmunoblastic T-cell lymphoma, n = 10; EBV-positive peripheral T-cell lymphoma, unspecified, n = 5; extranodal NK/T-cell lymphoma, nasal type, n = 4; and others, n = 3). Most patients (90%) had initial stage III/IV and 15 (60%) received ≥2 prior regimens. The objective response rate was 48% (90% CI, 31·0% to 64·3%; 12 of 25 patients), including five complete responses (20%) and seven partial responses (28%). Median DoR, PFS and OS were 10·1, 6·1, and 15·6 months, respectively. Common adverse events were peripheral neuropathy (48%), neutropenia (40%), thrombocytopenia (20%), and rashes (16%). Grade 3 and 4 adverse events were neutropenia (20%), thrombocytopenia (12%), and anemia (8%). Interpretation: Brentuximab vedotin is active and well tolerated in patients with relapsed or refractory EBV-positive and CD30-positive lymphomas. Trial Registration: (NCT02388490) Funding Statement: Takeda Pharmaceuticals Co. Ltd and Korea Health Industry Development Institute. Declaration of Interests: TMK received a research grant from AstraZeneca-KHIDI outside this work. DWK received travel and accommodation support for advisory board meeting attendance from Amgen and Daiichi-Sankyo outside this work. All other authors declare no competing interests. Seoul National University Hospital received grants from Alpha Biopharma, Amgen, Astrazeneca/Medimmune, Boehringer-Ingelheim, Daiichi-Sankyo, Hanmi, Janssen, Merus, Mirati Therapeutics, MSD, Novartis, ONO Pharmaceutical, Pfizer, Roche/Genentech, Takeda, TP Therapeutics, Xcovery and Yuhan. Ethics Approval Statement: The study was approved by the institutional review board at each participating site and written informed consent was obtained.

Brentuximab Vedotin As Single Agent in the Treatment of Relapsed/Refractory CD30 Positive Peripheral T-Cell Lymphoma Patients: A Phase 2 Study of the Fondazione Italiana Linfomi

Brentuximab Vedotin As Single Agent in the Treatment of Relapsed/Refractory CD30 Positive Peripheral T-Cell Lymphoma Patients: A Phase 2 Study of the Fondazione Italiana Linfomi

Real World Data on the Efficacy and Safety of Brentuximab Vedotin + Bendamustine in Relapsed/Refractory Hodgkin Lymphoma. Data collected from the Colombian Hematology Centers

Real World Data on the Efficacy and Safety of Brentuximab Vedotin + Bendamustine in Relapsed/Refractory Hodgkin Lymphoma. Data collected from the Colombian Hematology Centers

Efficacy and safety of brentuximab vedotin plus bendamustine in advanced‐stage primary cutaneous T‐cell lymphomas

Efficacy and safety of brentuximab vedotin plus bendamustine in advanced‐stage primary cutaneous T‐cell lymphomas

Brentuximab vedotin as a salvage treatment for relapsed and refractory Hodgkin lymphoma patients in Taiwan

Hodgkin lymphoma (HL) is a highly curable hematologic malignancy. Relapsed/refractory (R/R) HL is an important clinical challenge, despite advances in treatment. Brentuximab vedotin (BV) is highly effective in R/R HL in the western world. However, there are no real-world data on the use of BV in the Asian population. Our study aimed to evaluate the efficacy and safety of BV as salvage therapy in R/R HL patients in Taiwan. We recruited 20R/R HL patients who received BV at National Taiwan University Hospital. BV was administered at 1.8mg/kg once every 3 weeks. The median number of systemic treatment received before BV was three. The overall response rate was 73.7% with a complete remission rate of 21.1% in R/R HL. Overall survival was not reached and progression-free survival was 6.8 months. BV could strengthen disease control before transplantation and improve post-transplant outcomes, even among those heavily pretreated patients, without significant overlapping toxicities with prior therapies. Our data suggest that BV is well tolerated and effective in the treatment of Asian patients with R/R HL. BV may offer long-term disease control in selected patients.

PS1070 THE ECHELON‐2 TRIAL: RESULTS OF A RANDOMIZED, DOUBLE‐BLIND PHASE 3 STUDY OF BRENTUXIMAB VEDOTIN AND CHP (A+CHP) VERSUS CHOP IN FRONTLINE TREATMENT OF PATIENTS WITH CD30+ PERIPHERAL T‐CELL LYMPHOMAS

Please indicate where the abstract has been published before: The data in this abstract have been published in the Lancet (Horwitz 2019).Background:Peripheral T‐cell lymphoma (PTCL) is a heterogeneous group of aggressive non‐Hodgkin lymphoma (NHL) accounting for approximately 10% of all NHL cases worldwide, with a higher incidence reported in certain Asian countries. The most common frontline regimen for PTCL is cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP‐like regimens; however, anthracycline‐containing regimens result in a low rate of complete remission (CR) (Savage K, et al. Ann Oncol 2004). Based on the encouraging activity and manageable safety profile observed in a phase 1 study (Fanale M, et al. Blood 2018), the ECHELON‐2 trial was initiated to compare the efficacy and safety of brentuximab vedotin, cyclophosphamide, doxorubicin, and prednisone (A+CHP) versus CHOP for the treatment of CD30‐positive PTCL.Aims:To compare the effects of frontline brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone (A+CHP) versus CHOP as frontline therapy in patients with CD30‐positive peripheral T‐cell lymphoma (PTCL).Methods:ECHELON‐2 (ClinicalTrials.gov No. NCT01777152) is a phase 3, randomized, double blind, double‐dummy, placebo controlled, active‐comparator, multicenter study. Eligible adults with previously‐untreated CD30‐positive PTCL (targeting 75% ± 5% with systemic anaplastic large cell lymphoma [sALCL]) were randomized 1:1 to receive either A+CHP or CHOP for 6 or 8 21‐day cycles. Randomization was stratified by histological subtype as per local pathology assessment and by international prognostic index (IPI) score. The primary endpoint, progression free survival (PFS) per blinded independent central review (BICR), was analyzed for the intent‐to‐treat population. Key secondary endpoints were overall survival (OS), PFS in sALCL, CR rate, and objective response rate (ORR). Consolidative stem cell transplantation or radiotherapy was permitted at the investigator's discretion after end of treatment.Results:A total of 452 patients were enrolled between January 2013 and November 2016 and 226 patients were randomly assigned to each arm. Overall, the median age was 58 years (range, 18 to 85). The study enrolled patients with advanced disease (Stage III [27%] and Stage IV [53%]; IPI ≥2 [78%]) and most patients (316 patients [70%]) had sALCL (218 patients [48%] anaplastic lymphoma kinase [ALK]‐negative and 98 patients [22%] ALK‐positive). The hazard ratios of both PFS (0.71 [95% confidence interval {CI}: 0.54, 0.93], P = 0.01) and the OS (0.66 [95% CI: 0.46, 0.95], P = 0.02) favored A+CHP over CHOP. The median PFS was 48.2 months (95% CI: 35.2, not evaluable) versus 20.8 months (95% CI: 12.7, 47.6) for A+CHP and CHOP, respectively. The 3‐year PFS was 57.1% (95% CI: 49.9, 63.7) for A+CHP compared with 44.4% (95% CI: 37.6, 50.9) for CHOP. Median OS was not reached for either arm. Adverse events (AEs), including incidence and severity of neutropenia and peripheral neuropathy, were similar between arms. AEs leading to death occurred in 7 patients (3%) in the A+CHP arm and 9 patients (4%) in the CHOP arm.Summary/Conclusion:Frontline treatment with A+CHP is superior to CHOP for patients with CD30‐positive PTCL as demonstrated by a statistically significant improvement in PFS and OS, with a manageable safety profile.image

Brentuximab vedotin and ESHAP is highly effective as second-line therapy for Hodgkin lymphoma patients (long-term results of a trial by the Spanish GELTAMO Group)

BackgroundIn this work, we assessed the efficacy and safety of brentuximab vedotin (BV) plus ESHAP (BRESHAP) as second-line therapy for Relapsed/Refractory Hodgkin lymphoma (RRHL) to improve the results before autologous stem-cell transplantation (ASCT). Patients and methodsThis was a multicenter, open-label, phase I–II trial of patients with RRHL after first-line chemotherapy. Treatment had three 21-day cycles of etoposide, solumedrol, high-dose AraC, and cisplatin. BV was administered at three dose levels (0.9, 1.2, and 1.8 mg/kg) intravenous on day ‒1 to 3 + 3 cohorts of patients. Final BV dose was 1.8 mg/kg. Responding patients proceeded to ASCT, followed by three BV courses (1.8 mg/kg, every 21 days). Main end points for evaluation were maximum tolerable dose and overall and complete response (CR) before ASCT. ResultsA total of 66 patients were recruited (median age 36 years; range 18–66): 40 were primary refractory, 16 early relapse and 10 late relapse. There were 39 severe adverse events were reported in 22 patients, most frequently fever (n = 25, 35% neutropenic), including 3 deaths. Grade 3–4 hematological toxicity presented in 28 cases: neutropenia (n = 21), thrombocytopenia (n = 14), and anemia (n = 7). Grade ≥3–4 extrahematological adverse events (≥5%) were non-neutropenic fever (n = 13) and hypomagnesaemia (n = 3). Sixty-four patients underwent stem-cell mobilization; all collected >2×10e6/kg CD34+ cells (median 5.75; range 2.12–33.4). Overall response before transplant was 91% (CI 84% to 98%), including 70% (CRs 95% CI 59% to 81%). 60 patients were transplanted with no failure engraftments. Post-transplant response was CR in 49 patients (82% CI 73% to 91%) and partial responses in six (10% CI 5% to 15%). After a mean follow-up of 27 months, the 30-month time to treatment to failure was 74% (95% CI 68% to 80%), progression-free survival 71% (95% CI 65% to 77%), and overall survival 91% (CI 84% to 98%). ConclusionBRESHAP looks a safe and effective pre-transplant induction regimen, does not jeopardize transplant and allows long-term remissions and survival.

Cost-effectiveness of brentuximab vedotin plus chemotherapy as frontline treatment of stage III or IV classical Hodgkin lymphoma

Objective: The ECHELON-1 trial demonstrated efficacy and safety of brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A + AVD) vs doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) as frontline therapy for stage III/IV classical Hodgkin lymphoma. This analysis evaluated the cost-effectiveness of A + AVD from a US healthcare payer perspective.Methods: The incremental cost-effectiveness ratio (ICER), defined as the incremental costs per quality-adjusted life year (QALY) gained, was estimated using a non-homogenous semi-Markov cohort model with health states defined on progression following frontline treatment, and for those with progression, receipt of autologous stem-cell transplant (ASCT), and progression after ASCT. Patients undergoing ASCT were classified as refractory or relapsed based on timing of progression. Probabilities of progression/death with frontline therapy were based on parametric survival distributions fit to data on modified progression-free survival (mPFS) from ECHELON-1. Duration of frontline treatment and incidence of adverse events were from ECHELON-1. Utility values for patients in the frontline mPFS state were based on EQ-5D data from ECHELON-1. Other inputs were from published sources. A lifetime time horizon was used. Costs and QALYs were discounted at 3%. Analyses were conducted alternately using data on mPFS for the overall and North American populations of ECHELON-1.Results: The ICER for A + AVD vs ABVD was $172,074/QALY gained in the analysis using data on mPFS for the overall population and $69,442/QALY gained in the analysis using data on mPFS for the North American population of ECHELON-1. The ICER is sensitive to estimated costs of ASCT and frontline failure.Conclusion: The ICER for A + AVD vs ABVD based on ECHELON-1 is within the range of threshold values for cost-effectiveness in the US. A + AVD is, therefore, likely to be a cost-effective frontline therapy for patients with stage III/IV classical Hodgkin lymphoma from a US healthcare payer perspective.Trial registration: ClinicalTrials.gov identifier: NCT01712490.

Brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma (ECHELON-2): a global, double-blind, randomised, phase 3 trial

Based on the encouraging activity and manageable safety profile observed in a phase 1 study, the ECHELON-2 trial was initiated to compare the efficacy and safety of brentuximab vedotin, cyclophosphamide, doxorubicin, and prednisone (A+CHP) versus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) for the treatment of CD30-positive peripheral T-cell lymphomas. ECHELON-2 is a double-blind, double-dummy, randomised, placebo-controlled, active-comparator phase 3 study. Eligible adults from 132 sites in 17 countries with previously untreated CD30-positive peripheral T-cell lymphomas (targeting 75% with systemic anaplastic large cell lymphoma) were randomly assigned 1:1 to receive either A+CHP or CHOP for six or eight 21-day cycles. Randomisation was stratified by histological subtype according to local pathology assessment and by international prognostic index score. All patients received cyclophosphamide 750 mg/m2 and doxorubicin 50 mg/m2 on day 1 of each cycle intravenously and prednisone 100 mg once daily on days 1 to 5 of each cycle orally, followed by either brentuximab vedotin 1·8 mg/kg and a placebo form of vincristine intravenously (A+CHP group) or vincristine 1·4 mg/m2 and a placebo form of brentuximab vedotin intravenously (CHOP group) on day 1 of each cycle. The primary endpoint, progression-free survival according to blinded independent central review, was analysed by intent-to-treat. This trial is registered with ClinicalTrials.gov, number NCT01777152. Between Jan 24, 2013, and Nov 7, 2016, 601 patients assessed for eligibility, of whom 452 patients were enrolled and 226 were randomly assigned to both the A+CHP group and the CHOP group. Median progression-free survival was 48·2 months (95% CI 35·2-not evaluable) in the A+CHP group and 20·8 months (12·7-47·6) in the CHOP group (hazard ratio 0·71 [95% CI 0·54-0·93], p=0·0110). Adverse events, including incidence and severity of febrile neutropenia (41 [18%] patients in the A+CHP group and 33 [15%] in the CHOP group) and peripheral neuropathy (117 [52%] in the A+CHP group and 124 [55%] in the CHOP group), were similar between groups. Fatal adverse events occurred in seven (3%) patients in the A+CHP group and nine (4%) in the CHOP group. Front-line treatment with A+CHP is superior to CHOP for patients with CD30-positive peripheral T-cell lymphomas as shown by a significant improvement in progression-free survival and overall survival with a manageable safety profile. Seattle Genetics Inc, Millennium Pharmaceuticals Inc, a wholly owned subsidiary of Takeda Pharmacuetical Company Limited, and National Institutes of Health National Cancer Institute Cancer Center.