Brentuximab Vedotin Monotherapy Research Articles

Brentuximab Vedotin Retreatment in Patients with Relapsed or Refractory Classical Hodgkin Lymphoma or Peripheral T-Cell Lymphoma: A Retrospective United States Claims Analysis.

Brentuximab vedotin (BV) monotherapy (BV-M) and combination (BV-C) therapies are safe and effective for classical Hodgkin lymphoma (cHL) and CD30-expressing peripheral T-cell lymphomas (PTCLs). Although the sample sizes have been small (12-29 patients), in clinical studies, response rates of 53-88% have been reported for BV retreatment in patients with an initial BV response. We evaluated the real-world characteristics and treatment patterns of cHL/PTCL patients who received BV and were retreated in the United States. Symphony Health Patient Claims (11/2013-1/2022) were retrospectively analyzed to identify cHL/PTCL patients treated with BV and retreated with BV-M, BV-C, or non-BV therapy. Patient characteristics were described by retreatment, and predictors of BV-M retreatment were identified. Among the cHL and PTCL patients treated with BV (n = 6442 and 2472, respectively), 13% and 12%, respectively, were retreated with BV; the median times from initial BV to BV-M retreatment were 5 and 7 months, respectively; and the numbers of BV-M retreatment doses were 4 and 5, respectively. Among cHL patients, the predictors of BV-M retreatment were age (18-39 vs. ≥60 years), sex (women vs. men), and previous stem cell transplantation (yes vs. no). Among PTCL patients, the only predictor of BV-M retreatment was systemic anaplastic large-cell lymphoma subtype (yes vs. no). Real-world data support clinical study results suggesting earlier BV treatment be considered, as BV retreatment may be an option.

Brentuximab vedotin and chemotherapy in relapsed/refractory Hodgkin lymphoma: a propensity score–matched analysis

AbstractSeveral single-arm studies have explored the inclusion of brentuximab vedotin (BV) in salvage chemotherapy followed by autologous stem cell transplantation (ASCT) for relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL). However, no head-to-head comparisons with standard salvage chemotherapy have been performed. This study presents a propensity score–matched analysis encompassing individual patient data from 10 clinical trials to evaluate the impact of BV in transplant-eligible patients with R/R cHL. We included 768 patients, of whom 386 were treated with BV with or without chemotherapy (BV cohort), whereas 382 received chemotherapy alone (chemotherapy cohort). Propensity score matching resulted in balanced cohorts of 240 patients each. No significant differences were observed in pre-ASCT complete metabolic response (CMR) rates (P = .69) or progression free survival (PFS; P = .14) between the BV and chemotherapy cohorts. However, in the BV vs chemotherapy cohort, patients with relapsed disease had a significantly better 3-year PFS of 80% vs 70%, respectively (P = .02), whereas there was no difference for patients with primary refractory disease (56% vs 62%, respectively; P = .67). Patients with stage IV disease achieved a significantly better 3-year PFS in the BV cohort (P = .015). Post-ASCT PFS was comparable for patients achieving a CMR after BV monotherapy and those receiving BV followed by sequential chemotherapy (P = .24). Although 3-year overall survival was higher in the BV cohort (92% vs 80%, respectively; P < .001), this is likely attributed to the use of other novel therapies in later lines for patients experiencing progression, given that studies in the BV cohort were conducted more recently. In conclusion, BV with or without salvage chemotherapy appears to enhance PFS in patients with relapsed disease but not in those with primary refractory cHL.

Bendamustine Plus Brentuximab Has Superior Efficacy to Brentuximab Monotherapy As Third-Line Treatment for Classical Hodgkin Lymphoma: A Real-World, Multicentre UK Analysis

Purpose: The introduction of targeted agents has been a major advance in the treatment of classical Hodgkin lymphoma (HL) but the optimal application and sequencing of these agents is unclear. The CD30-targeted antibody-drug conjugate brentuximab vedotin (BV) is licensed for treatment of relapsed and refractory (R/R) HL as monotherapy and is available in the United Kingdom as third-line (3L) therapy for HL. BV has been evaluated in combination with chemotherapy in single-arm trials with very promising results, but randomised data are lacking. The aim of this analysis was to compare the efficacy of BV monotherapy with BV plus bendamustine (BVB) as 3L treatment of HL in a real-world UK cohort. Methods: Data were retrospectively collectively for consecutive patients receiving treatment for R/R HL with intent to consolidate with stem cell transplant (SCT) between 01/2015 and 12/2019 at 11 UK centres. Use of BVB was principally determined by availability, due to regional differences in BV funding in the UK, rather than patient disposition. Response was assessed by PET according to the Lugano Classification. Most analyses use descriptive statistics. Time-to-event analyses are measured from the start of 3L treatment until the first event (death for overall survival and death or further therapy for treatment failure) with groups compared using Kaplan Meier survival analysis and Cox regression. Results: 96 patients received BV and 30 received BVB. Baseline demographics are provided in the Table. Patients receiving BVB were slightly younger in age at diagnosis (p=0.031), but a slightly higher proportion had primary refractory disease (p=0.16) and failed to respond to second-line therapy (p=0.034). Numerically fewer patients in the BVB arm had received prior SCT (p=0.16). Patients received a median of 4 cycles of BV monotherapy (range 3 - 5). Patients treated with BVB received a median of 3 cycles of bendamustine (IQR 2 - 4) and 4 cycles of BV (IQR 3 - 5); 2 patients discontinued bendamustine after 1 cycle due to adverse reactions. Complete metabolic response was achieved in 34 patients (37.4%) with BV and 22 patients (73.3%) with BVB, with overall response rates of 57.3% and 93.3%, respectively (OR 9.2; 95% CI: 2.06 - 40.86; p=0.004). SCT consolidation was performed after 3L treatment in 33 patients (34.4%) following BV (26 autologous, 7 allogeneic) and 22 patients (73.3%) after BVB (17 autologous, 5 allogeneic). Median follow-up was 30.1 months after BV (IQR: 15.3 - 46.8) and 18.1 months after BVB (15.4 - 29.8). Freedom-from-treatment-failure (FFTF) rates at 18 months were 41.5% (95% CI: 30.8 - 51.8) after BV and 62.9% (39.3 - 79.4) after BVB (HR 0.45, 95% CI 0.23 - 0.88; p=0.019; see Figure). Overall survival rates at 18 months were 76.9% (66.0 - 84.7) after BV and 88.4% (68.1 - 96.1) after BVB (HR 0.37, 95% CI 11 - 1.23; p=0.11. There were 29 deaths following BV, including 17 (17.7%) due to HL, 6 (6.3%) due to toxicity of SCT or subsequent treatment and 6 (6.3%) due to other causes/unknown. There were 3 deaths following BVB, all due to toxicity of SCT or subsequent treatment (10%). Eight patients received single-agent bendamustine after failure of BV monotherapy, at a median of 2.4 months after commencing BV. The median number of bendamustine cycles delivered was 2 (range 1 - 6). The overall response rates was 62.5%. Two patients (25%) achieved complete metabolic response; both underwent subsequent SCT. Conclusion: In this retrospective analysis, use of BVB as 3L treatment for R/R HL was associated with higher response rates, transplant rates and FFTF compared with BV monotherapy. Although toxicity data were not available, our results are otherwise consistent with phase 2 trial data with BVB as second-line therapy (LaCasce, Blood 2018;132:40, Broccoli, Blood Cancer Journal 2019;9:100). These data demonstrate that BVB is a highly effective regimen in R/R HL, and support its use in transplant-fit patients.

Outcomes in Patients with Classical Hodgkin Lymphoma Refractory or Intolerant to Brentuximab Vedotin and Anti-PD-1 Therapy: Real World Analysis from 14 U.S. Academic Centers

Background: Brentuximab vedotin (BV) and anti-PD-1 therapies (nivolumab and pembrolizumab) have changed the therapeutic landscape for patients (pts) with classical Hodgkin lymphoma (cHL) over the past decade. Although first proven to be beneficial in relapsed and refractory cHL, these therapies have moved earlier in the treatment algorithm given superior response rates and survival compared to cytotoxic chemotherapy alone. However, there is limited data regarding outcomes in pts who progress after both BV and anti-PD-1 therapies (double refractory, DR) or become intolerant (INT) of these therapies. Knowledge of outcomes in this subset of pts is important as BV and anti-PD-1 therapies are increasingly used in front-line treatment and early relapsed cHL. Methods: We conducted a retrospective study of adult pts from 14 U.S. academic medical centers who developed DR cHL or became INT of BV and/or anti-PD-1 therapy between January 2011 and December 2021. DR was defined as treatment failure (evidence of progression by imaging or biopsy) during therapy or within 3 months of the last dose of both BV and anti-PD-1 therapy. INT was defined as any toxicity limiting further cycles of BV or anti-PD-1 therapy. Pts with INT were either intolerant to both BV and anti-PD-1 or intolerant and refractory to BV or anti-PD-1. The primary endpoint was assessment of overall survival from time of cHL diagnosis (OS-1) and from DR or INT (OS-2). Secondary endpoints included description of pt characteristics developing DR or INT cHL, estimate of OS comparing DR versus INT, and estimate of OS stratified by prior autologous stem cell transplant (ASCT) at the time of DR/INT. Time-to-event analyses were evaluated by Kaplan-Meier methodology. INT pts were not included in time to progression (TTP) analysis for initial BV or anti-PD-1 therapy. Results: 158 pts were eligible. Clinical characteristics at diagnosis included median age 33 years (range 16-89), 61% male, 77% white race, 66% nodular sclerosing subtype, 47% stage IV, and 56% with B symptoms. Front-line treatment was ABVD/AVD in 122 pts (77%) and BV or anti-PD-1 therapy in 28 pts (18%). 60% had primary refractory cHL (n=94). Table 1 describes pt characteristics in detail. Initial BV treatment was after a median of 2 lines of therapy (LOT) (range 0-7). The majority (60%, n=94) were treated with BV monotherapy and 15% (n=24) were treated with BV combined with anti-PD-1 therapy. Median TTP of BV refractory pts was 168 days (95%CI 138-190). Initial anti-PD-1 therapy was after a median of 3 LOT (range 0-12). Nivolumab was the most commonly used (72%) anti-PD-1 therapy. Median TTP of anti-PD-1 refractory pts was 223 days (95%CI 166-271). DR cHL was observed in 119 pts (75%), while 39 pts (25%) were INT. The median time from cHL diagnosis to DR/INT was 3.3 years (95%CI 0.5-23.1). At the time of DR/INT, 47% (n=75) had prior ASCT. The majority (87%, n=137) received subsequent LOTs after DR/INT (median 2, range 0-14). Table 1 describes DR/INT in detail. The median OS from the time of cHL diagnosis (OS-1) in all pts was 15.0 years (95%CI 9.4-20.9). There was no difference in OS-1 between DR and INT pts (log-rank p=0.83) or primary refractory and front-line relapsed pts (log-rank p=0.94). Pts who developed DR/INT at any time after ASCT had a significantly longer OS-1 compared to DR/INT without prior ASCT with a median OS of 19.1 years (95%CI 19.1-NR) versus 8.6 years (95%CI 5.3-15.0), respectively (log-rank p&amp;lt;0.001, Figure 1). Comparing pts with prior ASCT and no prior ASCT, the median age at DR/INT was 35 (range 20-75) versus 49 (range 18-90) years, Fisher's exact p=0.01. Adjusting for age at DR/INT did not impact the association between prior ASCT and improved OS, Cox proportional hazard ratio 0.48 (95%CI 0.25-0.90, p=0.02). Median OS from time of DR/INT (OS-2) was 7.4 years (95%CI 4.1-NR). OS-2 was not different between DR and INT pts (log-rank p=0.33). Conclusion: To our knowledge, this is the largest cohort of pts refractory to, or intolerant of BV and anti-PD-1 therapy. OS was longer than anticipated both from diagnosis and from time of DR/INT. Pts who were DR/INT after ASCT had a significantly longer OS. Further investigation is needed to determine if OS differences by ASCT may be due to disease biology or sequencing of therapies. Importantly, OS-2 serves as a benchmark for future clinical trials evaluating DR/INT cHL pts.

Brentuximab Vedotin Combined with Chemotherapy in the Treatment of Pediatric Patients with R/R Hodgkin Lymphoma: Results of a Real World Setting Study

INTRODUCTION: Hodgkin Lymphoma (HL) is a familiar malignant lymphoma of the lymphatic system that accounts for 10% of all lymphoma diagnoses and 5% of lymphoma-related deaths. According to statistics, the incidence of HL in children and adolescents (0-19 years old) in China is about 1.78/million, and an average of 569 new cases are estimated annually from 2019 to 2021 . Brentuximab vedotin (BV) is an antibody-drug conjugates (ADC) that selectively delivers monomethyl auristatin E, an antimicrotubule agent, into CD30-expressing cells. Most of the data on the efficacy and safety of BV came from prospective and retrospective studies in adults or foreign children, and there are insufficient data in Chinese children. The purpose of this study is to explore the efficacy and safety of BV Combined with chemotherapy in Chinese pediatric patients with refractory and/or relapsed Hodgkin's lymphoma. METHODS: Retrospective analysis of clinical data of 9 children with refractory and/or relapsed Hodgkin's lymphoma from October 2021 to May 2023 at Beijing Children's Hospital, Capital Medical University. Patients were classified according to: clinical stage(Ann Arbor stage), huge tumor, huge tumor in the mediastinum, symptoms of B, and whether multiple lymph nodes were involved. Among them, the low-risk group was IA, ⅡA without giant tumor. The middle risk group was IB and ⅢA without huge tumor. High-risk groups were patients with stage ⅡB, ⅢB, Ⅳ or (each stage) with large tumors, or children with &amp;gt; 4 lymph node regions. All patients received BV in combination with chemotherapy for at least 2 cycles, and patients were assessed for remission response according to the Revised Response Criteria for Malignant Lymphoma at the end of every 2 cycles and followed up until July 20, 2023. RESULTS: Totally 32 cycles of chemotherapy were recorded, including 36 doses of BV administration(Table 1). The overall response rate of the children after 2 cycles of treatment was 100%, and the complete response rate was 88.89%. After remission, 2 cases (P1, P2) were treated with BV single drug 1.8mg/kg, Q3W for 6 months, and 3 cases (P3, P4, P7) were treated with radiotherapy. Two patients (P5, P6) received sequential chemotherapy, and two patients (P8, P9) were followed by programmed cell death 1(PD-1) antibody maintenance treatment for 6 months. After receiving PD-1 antibody for 6 months, 1 patient (P9) was transferred to BV monotherapy for maintenance, with 18 times planned. 2 cases (P1, P2) were then treated with autologous stem cell transplantation. None of the children developed disease progression during treatment. All patients successfully completed all planned dosage of BV, and serious adverse events were dominated by grade 3 or higher hematocrit, none of which interfered with normal treatment. Interpretation. BV had demonstrated the better efficacy and tolerable safety profile in the treatment of refractory and/or relapsed Hodgkin's lymphoma in children. CONCLUSIONS: BV has been approved by National Medical Products Administration in China since 2020, the clinical cases are mostly from adult lymphoma patients, and children data of in China is rare. In this study, we retrospectively reviewed and analyzed the data of BV combined chemotherapy in the treatment of refractory and relapsed Hodgkin lymphoma from single center, and found that the treatment response was rapid, continuousand safe. However, this study is a single-center retrospective study with a small sample size So We are conducting a prospective study of BV in first-line Hodgkin lymphoma children patients in China and aiming to generate more data for this specific population.

The role of radiotherapy in patients with refractory Hodgkin's lymphoma after treatment with brentuximab vedotin and/or immune checkpoint inhibitors

BackgroundApproximately 10%–30% of patients with Hodgkin's lymphoma (HL) experience relapse or refractory (R/R) disease after first-line standard therapy. Brentuximab vedotin (BV) and immune checkpoint inhibitors (ICIs) have important roles in the salvage treatment of R/R HL. However, subsequent treatment for HL refractory to BV and/or ICI treatment is challenging. MethodsWe retrospectively analyzed patients in two institutions who had R/R HL, experienced BV or ICI treatment failure, and received radiotherapy (RT) thereafter. The overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS) were analyzed. ResultsOverall, 19 patients were enrolled. First-line systemic therapy comprised doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD, 84.2%); AVD plus ICIs (10.5%); and bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP, 5.3%). After first-line therapy, 15 (78.9%) and four patients (21.1%) had refractory disease and relapsed, respectively. After R/R HL diagnosis, six (31.6%), two (10.5%), and 11 (57.9%) patients received BV and ICIs concurrently, BV monotherapy, and ICI monotherapy, respectively. All patients received intensity-modulated RT (n = 12, 63.2%) or volumetric modulated arc therapy (VMAT; n = 7, 36.8%). The ORR as well as the complete response (CR) rate was 100%; the median DOR to RT was 17.2 months (range, 7.9–46.7 months). Two patients showed progression outside the radiation field; one patient had extensive in-field, out-of-field, nodal, and extranodal relapse. With a median follow-up time of 16.2 months (range, 9.2–23.2 months), the 1-year PFS and OS were 84.4% and 100%, respectively. PFS was associated with extranodal involvement (P = 0.019) and gross tumor volume (P = 0.044). All patients tolerated RT well without adverse events of grade ≥ 3. ConclusionRT is effective and safe for treating HL refractory to BV or ICIs and has the potential to be part of a comprehensive strategy for HL.

The combination of brentuximab vedotin and chidamide synergistically suppresses the proliferation of T-cell lymphoma cells through the enhancement of apoptosis

PurposePeripheral T-cell lymphoma (PTCL) is an aggressive disease with a poor prognosis. Brentuximab vedotin (BV), an anti-CD30 monoclonal antibody linked to a microtubule-disrupting agent, has been approved for the treatment of PTCL. We evaluated a new effective combination partner of BV using non-clinical approaches that could potentially identify agents capable of improving survival times for patients with PTCL.MethodsA high-throughput screening test was used to select the most synergistic partner of BV from 14 candidate drugs that were under development or available in clinical practice for PTCL. HH cells, originating from an aggressive cutaneous T-cell lymphoma, were used as an experimental model of PTCL. Apoptotic effects of the synergistic partner of BV were further investigated in vitro and in vivo using HH-cell xenograft mice.ResultsChidamide (tucidinostat), a novel histone deacetylase inhibitor, was found to have the greatest synergistic effect with BV on HH cells. The combined effects of chidamide and BV were demonstrated in a study of HH-cell xenograft mice; mean tumor size following combined treatment was 22% of that observed in the control group, compared with 71% and 58% following chidamide and BV monotherapy, respectively. Further investigations in vitro and in vivo revealed that the levels of an anti-apoptotic protein, Bcl-2, and a rate-limiting factor of DNA replication, CDC45, were reduced in HH cells treated with chidamide combined with BV compared with the control group.ConclusionThe use of chidamide in conjunction with BV may positively affect and enhance T-cellular apoptotic pathways without offsetting each other.

Brentuximab Vedotin in Frontline Therapy of Hodgkin Lymphoma in Patients with Significant Comorbidities Ineligible for Standard Chemotherapy (SGN35-015 Part E)

Brentuximab vedotin (BV) is approved for the treatment of adults with treatment-naïve stage III or IV classical Hodgkin lymphoma (cHL) combined with doxorubicin, vinblastine, and dacarbazine (AVD) and targets CD30, a receptor expressed on the Reed Sternberg cells. Treatment with BV plus AVD has demonstrated improved overall survival (OS) (6-year OS estimate of 93.9% vs 89.4%; HR, 0.59; 95% CI, 0.40-0.88; P=0.009) compared with the standard chemotherapy combination of doxorubicin, bleomycin, vinblastine, and dacarbazine (Ansell 2022). For patients (pts) newly diagnosed with cHL, current treatment options have improved pt outcomes in recent years, but survival rates are still very low for those with significant comorbidities. Pts with comorbid conditions can have poor outcomes due to decreased ability to tolerate dose intensity, increased treatment-related toxicity, and cHL relapse. This study is evaluating the efficacy and safety of single-agent BV as frontline therapy in cHL pts who are ineligible for conventional combination chemotherapy because of comorbidities. SGN35-015 Part E (NCT01716806) was a phase 2, open-label study of BV as frontline cHL therapy. Eligible pts (≥18 years) were unfit for initial conventional combination chemotherapy for cHL as documented by a modified Cumulative Illness Rating Scale score ≥10 or because they required or depended on others for instrumental activities of daily living. Pts received BV (1.8 mg/kg) on Day 1 of each 3-week cycle for up to 16 cycles. Granulocyte colony-stimulating factor prophylaxis was not required. The primary endpoint, objective response rate (ORR), was assessed by Blinded Independent Central Review (BICR) according to the Modified Lugano Criteria (Cheson 2014). Key secondary endpoints included safety, duration of response (DOR), complete response (CR) rate using the Lugano Criteria (Cheson 2014), duration of CR, progression-free survival (PFS), and OS. Thirty pts with cHL received BV and the median age was 76 years (range, 54 to 93 years). Most pts were female (53%) and had a disease stage of II (37%) or III (37%), an Eastern Cooperative Oncology Group (ECOG) performance status of ≥2 (50%; 10 pts [33%] and 5 pts [17%] had an ECOG performance status of 2 and 3, respectively). The median treatment duration was 18 weeks (range, 1 to 50 weeks). Per BICR, the ORR was 60% (18/30) (95% CI: 40.6%, 77.3%), including 33% (10/30) with a CR and 27% (8/30) with a partial response. Six pts (20%) did not respond to treatment: 1 (3%) with progressive disease and 5 (17%) with stable disease; one pt (3%) was not evaluable and the remaining 5 pts (17%) did not have postbaseline responses, either because of death before first scheduled response assessment or not yet reaching the first scheduled response assessment. Median DOR was 7.4 months (95% CI: 7.4 months, not estimable) and median PFS was 8.7 months (95% CI: 5.1 months, not estimable). Median duration of CR was not estimable (95% CI: 7.4 months, not estimable). With a median follow-up of 14.6 months (range, 0 to 44 months), the 2-year OS rate was 70% (95% CI: 48%, 84%). A total of 18 pts (60%) experienced grade ≥3 treatment-emergent adverse events (TEAEs). The most common grade ≥3 TEAEs were fatigue (n=3; 10%), acute kidney injury, anemia, atrial fibrillation, back pain, gait disturbance, hypoxia, neutrophil count decreased, pneumonia, sepsis, syncope, and vomiting (n=2 each; 7%). Nine pts (30%) discontinued treatment because of a TEAE; 1 death due to a TEAE (failure to thrive) was considered treatment-related. Thirteen percent (n=4) of pts experienced grade ≥3 peripheral neuropathy. In pts with cHL who are unfit for initial conventional chemotherapy due to comorbidities, BV monotherapy as frontline treatment appears effective, has an acceptable safety profile, and despite the small sample size could be considered as an option for pts with cHL who are unfit for conventional chemotherapy.

Outcomes in pediatric relapsed/refractory anaplastic large cell lymphoma: A multi-institutional retrospective analysis.

10032 Background: Treatment options for relapsed or refractory (R/R) anaplastic large cell lymphoma (ALCL) have increased in the era of targeted therapies such as brentuximab vedotin (BV) and Anaplastic Lymphoma Kinase (ALK)-inhibitors. However, there is no standard treatment and limited published data evaluating their use in this patient population. Methods: We conducted a retrospective, multi-institutional study of patients &lt;22 yrs old at initial diagnosis with R/R ALCL treated between 2011-2021 across 18 institutions. Results: We identified 85 patients with R/R ALCL (median age at initial diagnosis 12 yrs, 67% male, 96% ALK+). Treatment for initial diagnosis included ALCL99 (31%), ANHL12P1 + BV (32%), ANHL12P1 + crizotinib (CZ) (11%), ANHL0131 (14%), or other (13%). Median time from diagnosis to relapse was 0.7 yrs (range 0.2-10.8 yrs) with sixteen patients (18%) relapsing on initial chemotherapy. Stage at relapse for 82 ALK+ patients: I (9%), II (15%), III (41%), IV (35%). Initial re-induction regimens shown in the table. Fifty-nine (72%) patients received a hematopoietic stem cell transplant (HSCT), 11 autologous and 49 allogeneic with one receiving both. Of 59 transplanted patients, 10 relapsed (6 allo 4 auto) and 7 died. All but one of the patients who relapsed post-HSCT responded to additional therapy and remain alive. Of 23 ALK+ patients who never had a transplant, 4 patients died and 19 are alive in remission. Eleven remain on active therapy (6 CZ, 3 BV, 1 BV+CZ, 1 vinblastine) with eight off therapy. Patients who received a transplant more likely to be off therapy and alive. Duration of treatment for patients receiving BV or the ALK-inhibitor CZ varied widely (BV 1-11 yrs; CZ 2-10 yrs) with 20 patients continuing on therapy at the time of data collection. Five-year overall survival for patients with or without transplant was 91% (CI 84-99%) and 86% (CI 73-100%) respectively. Conclusions: This is the largest collection of patients with R/R ALK+ ALCL treated in the era of targeted therapy. Patients achieved excellent responses to ALK-inhibitor or BV monotherapy, but questions remain about duration of therapy. Transplant may not be necessary for all R/R patients including those with high-risk disease. [Table: see text]

Brentuximab-vedotin in combination with cyclophosphamide, doxorubicin, prednisolone for the treatment of aggressive CD30-positive cutaneous T-cell lymphomas

Aggressive CD30-positive cutaneous T-cell lymphomas (CD30+CTCL) are associated with unfavorable prognosis. Anthracycline-based polychemotherapy (CHOP) and brentuximab-vedotin (BV) monotherapy are related to poor outcomes in case of extracutaneous involvement or rapidly-progressing disease. Our objective was to assess the effectiveness of BV + CHP in aggressive CD30+CTCL. We included 7 patients treated with BV + CHP from April 2015 to January 2022: 4 had mycosis fungoides with large-cell transformation, 2 had primary cutaneous anaplastic large-cell lymphoma, and 1 harbored a primary cutaneous aggressive epidermotropic CD8-positive T-cell lymphoma. After a median [IQR] follow-up of 17.2 [13.2–21.0] months, 6/7 patients achieved an ORR lasting ≥4 months. The median [IQR] duration of response was 9.5 [5.9–11.1] months and the median [IQR] progression free survival was 14.9 [11.6–16.4] months. Four patients displayed progression with a median (range) time to next treatment of 15.8 (6.5–16.3) months. Two grade-3 adverse events were reported: febrile neutropenia and thromboembolic event. BV + CHP displayed substantial antitumor activity and favorable safety profile in 7 patients with aggressive CD30+CTCL.

Efficacy and Safety of Retreatment with Brentuximab Vedotin in Patients with Relapsed or Refractory Classical Hodgkin Lymphoma or CD30-Expressing Peripheral T Cell Lymphoma

Introduction Brentuximab vedotin (BV) is approved for the treatment of adult patients (pts) with classical Hodgkin lymphoma (cHL), systemic anaplastic large cell lymphomas (sALCL) or other CD30-expressing peripheral T-cell lymphomas (PTCL). BV has been evaluated in combination with doxorubicin, vinblastine, and dacarbazine (A+AVD) in adult pts with advanced stage cHL in ECHELON-1 (Ansell S, 2022) and in combination with cyclophosphamide, doxorubicin, and prednisone (A+CHP) in pts with sALCL, PTCL-not otherwise specified (NOS), and angioimmunoblastic T-cell lymphoma (AITL) in ECHELON-2 (Horwitz S, 2022), demonstrating BV is well tolerated with a favorable efficacy profile in the first-line setting. Moreover, BV is approved as monotherapy for treatment of adults with cHL at high risk of relapse as consolidation therapy post autologous stem cell transplant, as well as in relapsed or refractory (r/r) sALCL. BV has also been studied in r/r cHL after auto-stem cell transplant (Younes A, 2012) and retreatment setting (Trümper L, 2020), with favorable efficacy. CD30 expression persists after BV treatment and SGN35-006 demonstrated that BV monotherapy is an effective retreatment option in pts with r/r cHL or sALCL who previously achieved an objective response with BV monotherapy (Bartlett N, 2014). Herein, we present efficacy and safety results from a phase 2 study, where BV was evaluated in pts with r/r cHL or CD30-expressing PTCL who previously received BV either alone or in combination. Methods SGN35-028 (NCT03947255) is a multicentered, single arm, phase 2 clinical trial that enrolled adult pts with r/r cHL and sALCL or other CD30-expressing PTCL who were previously treated with a BV-containing regimen at least 6 months prior that had evidence of an objective response, and subsequently experienced disease progression or relapse after discontinuing treatment. Pts were treated with BV 1.2 or 1.8 mg/kg intravenously every 3 weeks until disease progression or unacceptable toxicity. The primary endpoints were objective response rate (ORR) and the safety and tolerability of BV retreatment. Results Of the 12 pts enrolled, 11 received at least 1 dose of study treatment including 5 pts with cHL and 6 pts with PTCL (4 pts with sALCL, 1 pt with PTCL-NOS, 1 pt with AITL). Both pts with non-ALCL PTCL had CD30 expression on 1% of tumor cells. Of the 11 pts that received at least 1 dose of study treatment, most were Black or African American (55%), not of Hispanic, Latino, or Spanish origin (91%), and <65 years old (73%). Pts received a median of 8 doses of BV (range: 1, 16) over a median of 25 weeks (range: 3, 55), 3 pts (27%) had dose reductions. Three pts were still on treatment as of data cutoff date. For pts with cHL, median time from initial diagnosis to first dose was 76.2 months (range: 34, 162), 2 pts achieved complete response (CR) and 3 pts partial response (PR) on prior BV therapy, median time from completion of last BV therapy to first dose was 28.2 months, and median age was 31 years (range: 28, 55). The ORR per investigator assessment was 60% (95% CI: 14.7, 94.7) with 1 pt achieving CR. For pts with PTCL, median time from initial diagnosis to first dose was 31.2 months (range: 23, 138), 5 pts achieved CR and 1 pt PR on prior BV therapy, median time from completion of last BV therapy to first dose was 20.1 months, and median age was 63 years (range: 35, 77). The ORR per investigator assessment was 83% (95% CI: 35.9, 99.6) with 4 pts achieving CR. The 4 pts with sALCL had an ORR of 100% with a CR rate of 75%. Eight pts discontinued study treatment, 4 pts discontinued treatment due to disease progression, 2 pts due to investigator decision, and 2 pts due to treatment emergent adverse events (TEAEs), both with peripheral sensory neuropathy. Thirty-six percent of pts experienced ≥ Grade 3 treatment-related TEAEs, 2 (18%) each for neutropenia and peripheral sensory neuropathy and 1 (9%) each for amylase increased, fatigue, malaise, and nausea. One pt experienced a Grade 5 adverse event of decreased appetite related to progressive PTCL disease that was not treatment related. Conclusions Preliminary results from this study show BV is a viable retreatment option for adults with r/r cHL, sALCL, and PTCL. Moreover, safety results were consistent with the known safety profile and no new safety signals were observed. This study is ongoing, updated efficacy and safety results will be presented at the meeting.

Addition of Brentuximab Vedotin to Gemcitabine in Relapsed or Refractory T-Cell Lymphoma: Final Analysis of a Lysa Multicenter, Phase II Study. "the TOTAL Trial"

Background : Outcome of relapse/refractory (R/R) peripheral T-cell lymphoma (PTCL) patients (pts) is usually poor. [Mak, 2013]. Brentuximab vedotin (Bv) monotherapy is approved for R/R anaplastic large cell-lymphoma (ALCL) with long term responders [Pro, 2017] and for 1st line in association with polychemotherapy [Horwitz, 2019] in all CD30+ PTCL (with no restriction related to expression cut-off). We designed a phase 2 study for R/R CD30+ PTCL combining gemcitabine (G) and Bv with the aim to increase the overall response rate (ORR) by 15%, compared to gemcitabine monotherapy (35%) [O'Connor, 2019] and among secondary endpoints to evaluate BV maintenance and the impact of both CD30 expression and soluble CD30 (sCD30) on response and survival. Patients and Methods: : Patients with confirmed CD30+ (≥5%) PTCL with measurable disease who failed or were refractory to 1-3 systemic therapy (excluding G and Bv) and ECOG performance status < 3 were eligible. Pts received 4 (28-days) cycles of G and Bv induction phase (GBvIP) (G : 1000mg/m² at D1 and D15 plus Bv: 1.8 mg/kg at D8) followed, in pts with complete (CR) or partial remission (PR) and non-eligible for SCT, by up to 12 (21-days) cycles of Bv (1.8 mg/kg) maintenance phase (BvMP). The primary endpoint was ORR (CR + PR) according to Lugano criteria (CT-scan-based). CD30 expression was semi-quantitatively assessed by immunohistochemistry (IHC) and serum sCD30 levels were determined by ELISA. (NCT03496779). Results: From April 2018 to October 2019, 71 pts with PTCL (47 males, 24 females) were enrolled. Central pathology review according to 2017 WHO criteria found nodal TFH-PTCL (34 ; 47.9%) [including AITL (27 ; 38%) and other nodal PTCL-TFH (7 ; 9.9%)] ; ALK- ALCL (14 ; 27%) ; PTCL-NOS (9 ; 13%) ; ALK+ ALCL (5 ; 7%), EATL (2 ; 2.8%) and other entities (7 ; 9.9%). Median age was 66 years (20-79), 65 pts (91.6%) were stage III-IV. ECOG status was ≥ 2 in 45 pts (63%). The number of prior lines were 1 (57), 2 (11) or 3 (3) and 28 pts (39.4%) had a refractory disease. In intention to treat analysis, the ORR after GBvIP was 46.5% including CR (14;19.7%), PR (19;26.8%). Among the 33 responders, 27 initiated BvMP as well as 1 non responding pt (with SD but a complete metabolic response). The median number of BvMP cycles was 9 (range 1-12). At least one G≥3 AE were recorded in 58/71 pts during GBvIP and 11/28 pts during BvMP. AE led to treatment discontinuation in 9/71 pts (GBvIP) and 14/28 pts (BvMP). Overall a polyneuropathy of G≥1 was recorded in 9/71 pts (GBvIP) and 14/28 pts (BvMP). After a median follow-up of 26.5 (0.5-42.1) months (mo), the median progression free survival (PFS) and overall survival (OS) were respectively 4.5 mo (95%CI [3.5 - 10]) (Figure 1A) and 12.9 mo (95%CI [8.6 - 25.5]). Among the 33 pts in PR/CR after GBvIP, the duration of response since inclusion (DOR) was 15.8 mo (95%CI [10.4 - (-)]) By univariate analysis, ORR was negatively influenced by high LDH (p=0.008) with borderline impact of ECOG (p=0.058), and both PFS and OS were reduced by refractory disease status at screening (p=0.031 and p=0.007) and non-ALCL histology (p=0.049 and p=0.041). CD30 expression was investigated on tumor samples collected either at screening (55.5%) or (if not available) at diagnosis (39,7%) or at previous relapse (4.8%). In pts with ALCL, CD30 expression was constant and high (>75% of tumor cells) along with a significant higher level of sCD30 compared to non ALCL pts. In non ALCL pts, the median % of CD30-positive tumor cells was 12.5% [0 - 12.5]. Focusing on non-ALCL pts we found a high impact of sCD30 level >120 ng/mL on both ORR, DOR, PFS and OS while CD30 expression on tumor cells did not appear to influence the results. (Figure 1B ; Table 1) Conclusion : According to our initial hypothesis, the addition of Bv to G is active in R/R CD30+ PTCLs both in terms of ORR, CR. In responding pts, the DOR exceeding 15 mo with very long responders suggests the value of Bv maintenance. Not surprisingly ALCL were associated with better results, but this treatment is also effective in non ALCL pts including a significant proportion of TFH lymphoma pts. Besides ALCL pts, biomarkers are needed to predict which pts could benefit the most of Bv based therapy. In line with a previous report [Horwitz, 2014], we did not find a clear impact of CD30 expression on tumor cells, however we demonstrate that baseline serum sCD30 at treatment initiation was strongly correlated with both response and outcome. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Response to Brentuximab Vedotin by CD30 Expression in Non-Hodgkin Lymphoma.

BackgroundThe safety and efficacy of brentuximab vedotin (BV), an antibody-drug conjugate directed to the CD30 antigen, has been assessed in several trials in patients with peripheral T-cell lymphoma (PTCL), cutaneous T-cell lymphoma (CTCL), or B-cell non-Hodgkin lymphoma (NHL). The objective of this research was to examine the relationship between CD30 expression level and clinical response to BV.Patients and MethodsWe analyzed response in patients treated with BV monotherapy in 5 prospective clinical studies in relapsed or refractory PTCL, CTCL, or B-cell NHL. CD30 expression was assessed by immunohistochemistry (IHC) using the Ber H2 antibody for 275 patients.ResultsAcross all 5 studies, 140 (50.9%) patients had tumors with CD30 expression <10%, including 60 (21.8%) with undetectable CD30 by IHC. No significant differences were observed for any study in overall response rates between patients with CD30 expression ≥10% or <10%. Median duration of response was also similar in the CD30 ≥10% and <10% groups for all studies.ConclusionsIn this analysis of studies across a range of CD30-expressing lymphomas, CD30 expression alone, as measured by standard IHC, does not predict clinical benefit from BV, making the determination of a threshold level of expression uncertain.

PJP pneumonia in brentuximab vedotin recipients.

e19533 Background: Pneumocystis pneumonia (PJP) is a catastrophic infection seen in the context of low CD4 counts. Brentuximab vedotin (BV) is a drug antibody conjugate targeting CD30 and is used to treat patients with Hodgkin’s lymphoma (HL) and T-cell lymphoma (TCL). PJP prophylaxis is not currently recommended for patients receiving BV-based treatment despite co-expression of CD30 on CD4 cells. The frequency of PJP following BV remains poorly defined. Methods: We evaluated patients who received BV between January 1, 2011 and October 31, 2021 at Mayo Clinic for the development of PJP. Patient demographics and clinical characteristics including underlying disease, chemotherapy regimen, absolute lymphocyte count (ALC), and steroid exposure were collected. Patients who developed PJP more than 3 months after their last BV exposure were excluded. Results: Of 402 BV recipients identified, 63 received PJP prophylaxis and were omitted. Fourteen of the 339 (4.1%) not on prophylaxis developed PJP following BV. Those infected had a median age of 61 (22-87), 71% were male. The most common diagnoses were HL, TCL, and primary mediastinal B-cell lymphoma at rates of 57%, 21%, and 14% respectively. Therapy regimens included BV monotherapy, BV-CHP, and BV-AVD at rates of 43%, 21%, and 14% respectively. BV represented median 2nd line of therapy (1-10) and patients received median of 3 doses (1-10) prior to PJP diagnosis. Patients with PJP had median ALC of 620 (370-3500). 71.4% (10/14) had an ALC less than 750 and among those with ALC greater than 1000, 75% (3/4) had underlying diagnosis of HL. Three patients had CD4 count measured at time of PJP diagnosis with median value of 157 (5-175). 57.1% (8/14) had no steroid exposure beyond the treatment regimen. 14.3% (2/14) were on chronic doses of 5mg prednisone for autoimmune conditions. Short bursts of steroids (prednisone 40 mg) prior to PJP were seen in 21.4% (3/14) with median exposure of 8 days (7-10). One patient had prolonged steroid exposure but was weaned off 17 days prior to PJP diagnosis. 71.4% were older than 50 years at time of PJP. Conclusions: We observed rates of PJP above the commonly accepted threshold of 3.5% for recommending prophylaxis. Among patients with an ALC greater than 1000, 75% had HL raising the question of a qualitative defect in immunity. Close ALC monitoring is recommended for patients receiving BV with a low threshold to institute PJP prophylaxis, especially amongst those older than 50 or with a diagnosis of HL.[Table: see text]

Population-based cohort study of the efficacy of brentuximab vedotin in relapsed systemic anaplastic large-cell lymphoma using Public Health England data.

Systemic anaplastic large-cell lymphoma (sALCL) is a rare T-cell lymphoma associated with poor prognosis after relapse. The immunoconjugate brentuximab vedotin (BV) first became available for relapsed sALCL in England in 2013, following the results of a pivotal phase II study. We present a population-based study describing outcomes of relapsed sALCL in England after BV, using Public Health England data. We obtained information on all relapsed/refractory (r/r) sALCL patients ≥18 years treated with BV monotherapy in England between 1 January 2014 and 31 December 2019. The final cohort comprised 127 patients with a median age of 60 years (range 19-89). Eighteen (14·2%) had received stem cell transplant in first remission. Median two-year overall survival (OS) was 46·6%. The vast majority of deaths (59) occurred within 18 months, with very few events after this. Receipt of BV as second line compared to third or fourth line was associated with significantly improved survival (two-year OS 50·3% vs 29·7%, P = 0·03). There was no difference in OS for different subgroups, including anaplastic lymphoma kinase status, age, gender, or receipt of stem cell transplantation in first response. We report excellent survival following treatment with BV in a real-world setting, comparable with previous clinical trial data.

POPULATION‐BASED COHORT STUDY OF THE EFFICACY OF BRENTUXIMAB‐VEDOTIN IN RELAPSED SYSTEMIC ANAPLASTIC LARGE CELL LYMPHOMA USING PUBLIC HEALTH ENGLAND DATA

Systemic anaplastic large cell lymphoma (sALCL) is a rare T-cell lymphoma associated with poor prognosis after relapse. The immuno-conjugate Brentuximab Vedotin (BV) first became available for relapsed sALCL in England in 2013, following the results of a pivotal phase II study. We present a population-based study describing outcomes of relapsed sALCL in England after BV, using Public Health England (PHE) data. We obtained information on all relapsed/refractory (r/r) sALCL patients ≥18 years treated with BV monotherapy in England between 1st Jan 2014-31st Dec 2019. The final cohort comprised 127 patients with a median age of 60 years (range 19-89). 18 (14.2%) had received stem cell transplant in first remission. Median 2-year overall survival (OS) was 46.6%. The vast majority of deaths (59) occurred within 18 months, with very few events after this. Receipt of BV as second line compared to third or fourth line was associated with significantly improved survival (2-year OS 50.3% vs 29.7%, p = 0.03). There was no difference in OS for different subgroups, including ALK status, age, gender, or receipt of SCT in first response. We report excellent survival following treatment with BV in a real-world setting, comparable with previous clinical trial data.

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.

The Echelon-2 Trial: 5-Year 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-Positive Peripheral T-Cell Lymphoma

The Echelon-2 Trial: 5-Year 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-Positive Peripheral T-Cell Lymphoma

Frontline Brentuximab Vedotin As Monotherapy or in Combination for Older Hodgkin Lymphoma Patients

Introduction: Older patients with classical Hodgkin lymphoma (cHL) have poor outcomes relative to younger patients, often due to comorbidities and toxicities related to standard first-line (1L) chemotherapy (5-yr PFS: 30%-45% vs 75%-80%) (Evens 2008; Proctor 2009). Brentuximab vedotin (BV), a CD30-directed antibody-drug conjugate, has robust activity in patients refractory to several lines of chemotherapy. Methods: This phase 2, open-label study, SGN35-015 (NCT01716806), evaluated efficacy and tolerability of BV alone or combined with single-agents in treatment-naive cHL patients ≥60 yr. The full-analysis set (FAS) includes all patients who received BV (1.8 mg/kg IV). Patients in Part A received BV monotherapy on Day 1 of every 3-week cycle (n=26); Part B: BV+dacarbazine (DTIC; 375 mg/m2; n=19); Part C: BV+bendamustine (benda; 70 mg/m2; n=20); and Part D: BV+nivolumab (nivo; 3 mg/kg; n=20). The efficacy evaluable (EE) set includes FAS who had at least 1 post-baseline response assessment (n=25, 19, 17, 19). Results: Demographic characteristics were generally similar: median age 78, 69, 75, and 72 yr in Parts A, B, C, and D, respectively, and 62% of patients (range 45%-70%) reported impaired physical functioning at baseline. Most patients had disease stage III/IV (62%, 68%, 75%, 80%), were ECOG 0/1 (77%, 74%, 80%, 95%), and male (54%, 68%, 50%, 75%). Median time from diagnosis was 1.2 to 1.5 mo (FAS; 10 Jan 2020 data cutoff). ORR were high (92% [95% CI: 74%, 99%], 100% [95% CI: 82.4%, 100%], 100% [95% CI: 80.5%, 100%], 95% [95% CI: 74%, 99.9%]) at a median follow-up of 59.4, 58.6, 51.3, and 19.4 mo in the EE data set. Median PFS in the EE set was 10.5 mo (95% CI: 5.6, 77.5) with monotherapy and 46.8 mo (95% CI: 11.0, 68.7), 40.3 mo (95% CI: 4.8, NR), and not reached (95% CI: 9.4, NR) in the combination parts. Median OS in the FAS set was 77.5 mo (95% CI: 40.1, NR) with monotherapy; 64.0 (95% CI: 53.4, NR), 46.9 (95% CI: 6.8, NR), and not reached (95% CI: NR, NR) in the combination parts. Treatment-related adverse event (AE) ≥ Grade 3 occurred in 50%, 37%, 70%, and 60% of patients; peripheral neuropathy (PN) was most common (35%, 26%, 20%, 35%). Treatment-related serious AEs occurred in 12%, 11%, 40%, and 5% of patients. Part C enrollment (BV+benda) closed early due to multiple acute toxicities. There were no treatment-related deaths in any part of the study. The median treatment cycles per patient were 8.0, 12.0, 5.0, and 14.5. Treatment discontinuation due to related AEs occurred in 42%, 42%, 40%, and 30% of patients, most commonly due to PN (38%, 37%, 30%, 20%). Conclusions: Older patients with cHL and multiple comorbidities have very high response rates and a clinically meaningful improvement in PFS with BV as monotherapy or combined with other single agents and improved tolerability versus combination chemotherapy. Median overall survival exceeded 6 yrs with BV monotherapy. BV+nivo or BV+DTIC appeared to be the most reasonable combination treatment options in this study. Disclosures Yasenchak: BeiGene: Speakers Bureau; Seattle Genetics: Honoraria, Research Funding; Takeda: Honoraria. Bordoni:Takeda: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Guardant Health: Honoraria, Speakers Bureau; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses, Patents &amp; Royalties; Northside Hospital Cancer Institute: Other: Uncompensated relationship; Practice Point Communications: Other: Uncompensated relationship; Foundation Medicine: Membership on an entity's Board of Directors or advisory committees; Genentech: Honoraria, Speakers Bureau; G1 Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Patel-Donnelly:Gilead: Research Funding; Boston Biomedical: Research Funding; Roche: Research Funding; LAM Therapeutics: Research Funding. Goldschmidt:Amgen: Consultancy; Bristol-Myers Squibb: Speakers Bureau; Blue Ridge Cancer Care: Current Employment. Boccia:Rigel: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Incyte: Consultancy, Honoraria, Research Funding, Speakers Bureau; Genentech: Consultancy, Honoraria, Research Funding, Speakers Bureau; Daiichi Sankyo: Consultancy, Honoraria, Research Funding, Speakers Bureau; AstraZeneca: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau. Cline:Pfizer: Honoraria; Reflexion Medical: Consultancy, Other: Travel expenses; Texas Oncology: Current Employment. Sacchi:Bristol-Myers Squibb Company: Current Employment. Forero-Torres:Seattle Genetics, Inc.: Current Employment, Current equity holder in publicly-traded company. Sims:Seattle Genetics, Inc.: Current Employment, Current equity holder in publicly-traded company, Other: Travel expenses. Liu:Seattle Genetics, Inc.: Current Employment, Current equity holder in publicly-traded company. Friedberg:Roche: Other: Travel expenses; Portola Pharmaceuticals: Consultancy; Bayer: Consultancy; Astellas: Consultancy; Acerta Pharma - A member of the AstraZeneca Group, Bayer HealthCare Pharmaceuticals.: Other; Kite Pharmaceuticals: Research Funding; Seattle Genetics: Research Funding.

Addition of Brentuximab Vedotin to Gemcitabine in Relapsed or Refractory T-Cell Lymphoma: Results of a Lysa Multicenter, Phase II Study. “the TOTAL Trial”

Addition of Brentuximab Vedotin to Gemcitabine in Relapsed or Refractory T-Cell Lymphoma: Results of a Lysa Multicenter, Phase II Study. “the TOTAL Trial”