Brentuximab Vedotin In Combination Research Articles

Phase I Trial of Brentuximab Vedotin Plus Cyclosporine in Relapsed/Refractory Hodgkin Lymphoma

Introduction Treatment of relapsed/refractory (R/R) Hodgkin lymphoma (HL) following failure of brentuximab vedotin (BV) and PD-1 blockade is a major unmet need. Resistance to BV is associated with multidrug resistance gene 1 (MDR1) overexpression. There are pre-clinical data showing that MDR1 inhibitors such as cyclosporine (CsA) or verapamil (VRP) are synergistic with BV in BV-resistant HL cell lines. Preliminary results of a phase I study evaluating the safety and efficacy of combination of BV with CsA and VRP in R/R HL were previously reported. Here we report the final results of the completed study. Methods This is a single center, open-label phase I investigator-initiated study. Patients (pts) with HL whose disease had relapsed or was refractory to ≥1 prior lines of therapy were enrolled. The dose finding portion followed a 3+3 design with 4 planned dose levels (DL). BV was given at 1.2 mg/kg (DL1) or 1.8 mg/kg (DL2-4) intravenously every 3 weeks. Planned dose of CsA was 5 mg/kg (DL1-2) or 7.5 mg/kg (DL3-4) orally twice daily on days 1-5. Planned dose of VRP was 120 mg orally four times daily on days 1-5 (DL4). Each cycle was 3 weeks. Once the maximum tolerated dose (MTD) was determined, BV-refractory pts were enrolled in an expansion cohort at the MTD. Primary objective was to determine the MTD and safety of the combination. Secondary objectives were overall response rate (ORR), complete response (CR) rate, response duration (DOR), overall survival (OS), and progression-free survival (PFS). Results Twenty-nine pts were enrolled onto the study, 14 in the dose-finding portion and 15 in the dose expansion BV-refractory cohort. With respect to baseline characteristics, 38% of patients were female, 69% had advanced stage disease, 45% had extranodal disease, and 24% had B symptoms. Median age was 36 (20-69) and pts had a median of 5 (3-12) prior lines of therapy. All had prior BV (only 2 BV-sensitive) and 27 had prior PD-1 blockade. Four pts were treated on DL1, 22 on DL2, and 3 on DL3. MTD was DL2. DLTs observed were: DL1 10-day CsA (n=1) grade (Gr) 3 hyperbilirubinemia, abdominal pain, and hypertension, DL2 (n=1) Gr3 abdominal pain and Gr3-4 neutropenia, DL3 (n=2) Gr3 bone pain/constipation/Gr4 lymphopenia (n=1) and Gr3 hyperglycemia (n=1). Median duration of treatment was 3 (1-16) cycles. Most frequent adverse events (AEs) were nausea (90%), hypertension (90%), anemia (86%), fatigue (76%), neutropenia (76%), and leukopenia (76%). All pts had Gr3+ AEs with most frequent being neutropenia (62%). Reasons for treatment discontinuation included death (n=4), disease progression (n=10), toxicity (n=2), patient refusal (n=8), loss to follow-up (n=2), MD decision (n=1), proceeding to HCT (n=1), and study completion (n=1). Treatment-related death occurred in 3 pts (pneumonitis at DL1, respiratory failure and hypotension at DL2). The ORR/CR was 62%/24%. The median DOR and PFS was 5 months and median OS was not reached. Discussion The combination of BV and CsA was effective in BV-refractory R/R HL but was also associated with toxicity, including treatment-related deaths that led to early termination of the clinical trial. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

HL-300 Efficacy of Brentuximab Vedotin Plus Conventional Chemotherapy Regimens as Pre–Autologous Stem Cell Transplantation Re-Induction Salvage Therapy in Relapsed/Refractory Classical Hodgkin Lymphoma

Adding brentuximab vedotin (BV) to traditional chemotherapy protocols, followed by autologous stem cell transplantation (ASCT), has effected fundamental change in the treatment approach of relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL). Several studies have shown a superior rate of complete remission (CR) up to 70%-87% in patients receiving BV-based salvage chemotherapy. Previous studies exposed pre-ASCT PET-CT negativity as the most important factor affecting the post-transplant outcome. Therefore, our objective was to evaluate the efficacy of BV-chemotherapy regimens by PET CT assessment of response rate. Single-center, descriptive retrospective analysis of 20 patients with R/R cHL, eligible for ASCT, treated at the University Clinic for Hematology - Skopje between January 2017 and January 2022. We reviewed demographic and clinical characteristics pointing to disease stage and the presence of unfavorable prognostic factors, treatment, and outcome. Patients received BV-chemotherapy combinations, including BV-DHAP and BV-ICE, or PET-adapted sequential chemotherapy with BV followed by augmented ICE. In patients receiving a BV combination, PET-CT was performed after 3 cycles. In patients treated with sequential chemotherapy who did not achieve response by 3 cycles of BV and received augmented ICE, PET-CT was performed after the second cycle. Fourteen patients (70%) had refractory disease and 6 patients (30%) had relapsed disease (3 with early relapse). The majority were male (70%). The mean age at the time of assessment was 39 (range: 15-63). According to the EORTC staging system, 14 patients (70%) were initially defined to have advanced stage. Patients had received 1-3 previous treatment lines. Seven patients with refractory disease received BV-DHAP. After 3 cycles, PET negativity was achieved in 4 patients (57.1%) and these patients proceeded to ASCT. All 5 patients with relapsed disease treated with BV-DHAP achieved CR. Two patients with refractory disease received BV-ICE and both of them progressed. Among 5 patients with refractory disease receiving sequential therapy, CR was confirmed in 3 (60%). One patient with early relapse received BV-augmented ICE and achieved CR. BV-based salvage chemotherapy is an effective treatment strategy for patients with R/R cHL, and it is reasonable to be moved forward as standard second-line therapy in R/R CD30+ cHL.

Final results of brentuximab vedotin combined with ifosfamide-carboplatin-etoposide in first refractory/relapsed Hodgkin lymphoma: a lymphoma study association phase I/II study

This phase I/II study assessed the combination of brentuximab vedotin (BV) with ifosfamide-carboplatin-etoposide (ICE) as a second-line therapy in refractory/relapsed (R/R) classical Hodgkin lymphoma (cHL) patients. Phase I study was designed to determine the maximum tolerated dose (MTD) of BV (10 patients) and phase II evaluated the rate of complete metabolic response (CMR) after 2 cycles of BV-ICE (42 patients). There were no dose-limiting toxicities (DLT) during phase I recommending BV 1.8 mg/kg for phase II. Twenty-six patients (61.9%) achieved CMR after 2 cycles of BV-ICE and 37 patients (88%) were transplanted. With a median follow-up of 38 months, the 3-year progression free survival (PFS) and overall survival (OS) rate were 64.3% and 100%, respectively. Hematological toxicities (81%) and infections (21%) were the most frequent adverse event encountered BV-ICE regimen is feasible with manageable toxicities and could be an alternative to other salvage treatments. Trial Registration: ClinicalTrials.gov identifier: NCT02686346

Own experience in the treatment of primary refractory Hodgkin's lymphoma. Case report

Despite significant progress made in recent decades in the treatment of classical Hodgkin's lymphoma, in 1030% of patients develop a refractory course or relapse of the disease. The effectiveness of therapy of the second and subsequent lines is about 50%. A significant breakthrough in the treatment of recurrent/refractory forms of classical Hodgkin's lymphoma has been the introduction of targeted drugs. The inclusion of new drugs in previously standard rescue therapy regimens significantly improves the effectiveness of the therapy. A clinical case of treating a patient with the progression of classical Hodgkin's lymphoma after first-line therapy, the use of brentuximab vedotin in combination with bendamustine as a rescue therapy with the achievement of complete remission, followed by high-dose consolidation with autologous hematopoietic stem cell transplantation is presented.

Brentuxinmab vedotin, alone or combine with bendamustine in the treatment of natural killer T cell lymphoma.

Natural killer (NK)/T cell lymphoma is a highly aggressive subtype of non-Hodgkin lymphoma. The prognosis of patients with natural killer T cell lymphoma (NKTCL) remains poor. More potent treatment strategies are urgently needed to improve the survival of these patients with R/R NKTCL. CD30 expression has been reported to occur in about 40% of NK/T cell lymphoma. Brentuximab vedotin (BV), a monomethyl auristatin E conjugated CD30 antibody, targets CD30 to kill cancer cells. Therapeutic combination of BV and bendamustine has been shown to be highly effective in Hodgkin lymphoma. We investigated efficacy of BV in treating NKTCL as a single therapy, and in combination with bendamustine in vitro and in vivo. We determined CD30 expression levels in 6 NKTCL cell lines. The efficiency of lymphoma cell inhibition by BV correlates with CD30 expression. We also determined the efficacy of BV in combination with bendamustine and found synergistic effects with bendamustine in NKTCL. Combined BV and bendamustine treatment exerted synergistic antiproliferation effect and enhanced cell apoptotic in vitro and in vivo. Brentuximab vedotin and bendamustine synergistically arrested cell cycle at the G2/M phase in NKTCL cell lines. The combination of BV and bendamustine was demonstrated to synergistically damage DNA in NKTCL. This study provides a reference for possible application on using BV for the treatment of NKTCL, either as a single agent or in combination with bendamustine.

EL24 The current status of treatment for malignant lymphoma

The treatment of malignant lymphoma has undergone major changes in recent years. ABVD with or without radiotherapy for untreated Hodgkin lymphoma (HL) and CHOP-based combination therapy with anti-CD20 antibody rituximab for B cell non-Hodgkin lymphoma (B-NHL) have long been the standard of care. Type II anti-CD20 antibody obinutuzumab combination chemotherapy has become a new treatment option for indolent-B-NHL, and an antibody-drug conjugate against CD30 brentuximab vedotin combination chemotherapy has become the new treatment of choice for advanced-stage HL and CD30-positive T-NHL.

P1089: BRENTUXIMAB VEDOTIN, NIVOLUMAB, DOXORUBICIN, AND DACARBAZINE (AN+AD) FOR ADVANCED STAGE CLASSIC HODGKIN LYMPHOMA: PRELIMINARY SAFETY AND EFFICACY RESULTS FROM THE PHASE 2 STUDY (SGN35 027 PART B)

Background: Brentuximab vedotin (BV) and nivolumab are both active and well-tolerated in patients (pts) with classical Hodgkin lymphoma (cHL) and were previously studied in first salvage (overall response rate [ORR] 85%; complete response [CR] 67%) (Advani 2021) and as firstline (1L) therapy in older adults (ORR 95%; CR 79%) (Yasenchak 2019). The combination of BV plus nivolumab demonstrated promising activity as a frontline treatment option for pts over 60 yrs of age with cHL (Friedberg 2018). Additionally, in pts with non-bulky Stage I or II cHL, treatment with BV plus doxorubicin and dacarbazine (AD) resulted in a CR rate of 97% at end of treatment (EOT), as well as a promising 4-year progression-free survival (PFS) estimate of 91%. There were no cases of ≥Grade 3 peripheral neuropathy and only 9% were Grade 2 (Abramson 2021). Aims: This abstract will present the preliminary safety and efficacy results from Part B of the SGN35-027 study, which enrolled pts with Ann Arbor Stage II cHL with bulky mediastinal disease (defined as a single node or nodal mass ≥10 cm as determined by CT imaging), or Stage III or IV cHL. Methods: SGN35-027 (NCT03646123) is an open-label, multiple part, multicenter, phase 2 clinical trial. Pts received up to 6 cycles of AN+AD (consisting of BV 1.2 mg/kg, nivolumab 240 mg, doxorubicin 25 mg/m2, and dacarbazine 375 mg/m2). All study drugs were administered by IV infusion on Days 1 and 15 of each 28-day cycle. The primary endpoint was CR rate at EOT. Key secondary endpoints included safety, tolerability, ORR, and PFS. Disease response and progression was assessed by investigators using the Lugano Classification Revised Staging System for nodal non-Hodgkin and Hodgkin Lymphomas (Cheson 2014) and Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC) (Cheson 2016) at Cycle 2 and EOT. Results: In Part B, 58 pts were enrolled and 57 pts received at least 1 dose of study treatment. Of these 57 pts, 30 (53%) were male, 27 (47%) were female, 50 (88%) were white, 46 (81%) were not of Hispanic or Latino/a or Spanish origins, and 54 (95%) were <65 years old. Median age was 35 yrs (range: 19-78 yrs); 30% had Stage II cHL with bulky mediastinal disease, while 18% and 51% had Stage III and IV cHL, respectively. Of 58 pts enrolled, 52 (90%) completed treatment and 4 (7%) discontinued due to AEs. The most frequently reported TEAEs were nausea, fatigue, and diarrhea (70%, 51%, and 46% of pts, respectively). Grade 3 or higher TEAEs were reported in 30 pts (53%), with neutropenia and increased ALT in 5 pts (9%) being the most frequent. Treatment-related AEs occurred in 98% of pts; the most frequent were nausea, fatigue, and peripheral sensory neuropathy (65%, 46%, and 39% of pts, respectively). Treatment-related SAEs occurred in 8 pts (14%), of which pneumonitis was the most common (3 pts [5%]). Immune-mediated AEs were observed in 18 pts (32%), and hypothyroidism (4 pts [7%]) was the most frequently reported. No febrile neutropenia was observed, and there were no Grade 5 AEs. Preliminary results show at EOT, 52 pts had a response to treatment (ORR 93% [95% CI:82.7-98.0]), with 49 pts having a complete response (CR rate: 88% [95% CI: 75.9-94.8]). Summary/Conclusion: Preliminary results demonstrate that AN+AD has promising clinical activity and is well-tolerated, with no new safety signals observed. The omission of bleomycin and vinblastine may have contributed to the absence of certain AEs, such as febrile neutropenia. AN+AD may provide another active treatment option for patients with 1L advanced cHL.

P1178: BRENTUXIMAB VEDOTIN IN COMBINATION WITH LENALIDOMIDE AND RITUXIMAB IN PATIENTS WITH RELAPSED/REFRACTORY DLBCL: SAFETY AND EFFICACY RESULTS FROM THE SAFETY RUN-IN PERIOD OF THE PHASE 3 ECHELON-3 STUDY

Background: Patients (pts) with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who relapse after or are ineligible for hematopoietic stem cell transplant (HSCT) or chimeric antigen receptor T cell (CAR-T) therapy generally have poor outcomes. Preclinical data provide the rationale for combining brentuximab vedotin (BV), lenalidomide (len), and rituximab for the treatment of R/R DLBCL. BV+len showed promising clinical activity in a Phase 1 trial with a 57% overall response rate (ORR), 10.2-month median progression-free survival, and 14.3-month overall survival (Ward 2021). Aims: We report the results of the open-label safety run-in that was conducted prior to the randomized portion of the study. Methods: ECHELON-3 (NCT04404283) is a randomized, double-blind, placebo-controlled, active-comparator, multicenter Phase 3 study. Prior to randomization, an open-label safety run-in was conducted; pts received BV (1.2 mg/kg) and rituximab (375 mg/m2) both q3w, and len 20 mg qd. Pts must have received ≥2 prior lines of therapy and be previously treated with or were ineligible for HSCT or CAR-T, ECOG score ≤2, and PET-avid, bidimensional measurable disease (>1.5 cm by CT). Pts with negligible CD30 expression (<1%) were eligible. Response was assessed by the investigator according to the Lugano Classification Revised Staging System (Cheson 2014). Results: 10 pts with R/R DLBCL were enrolled. Median age was 70.5 years, 7 pts were male, and all had an ECOG ≤1. Median prior lines of therapy was 3 (range, 2 to 6); no pts received prior HSCT and 6 pts received prior CAR-T. At a median follow-up of 6.9 months (range, 2.3 to 14.1), the most common treatment emergent adverse events (TEAE) were fatigue (n=5), anemia (n=4) and constipation (n=4). Grade ≥3 events were experienced by 8 pts, most commonly anemia and pneumonia (n=3 each), and neutropenia and thrombocytopenia (n=2 each). Serious adverse events were observed in 7 pts. Seven pts each had BV and rituximab dose modifications, and 6 pts had a len dose modification. The most common reasons for any dose modification were anemia (n=3), neutropenia, peripheral neuropathy, or pneumonia (n=2 each). 4 pts discontinued treatment due to an AE, 2 of which were treatment related (n=1 each of Grade 2 fatigue; Grade 3 anemia). There was 1 death due to a TEAE that was not treatment related. The ORR (best response) was 70%, including 5 pts with a complete metabolic response and 2 pts with a partial metabolic response; 3 pts had progressive disease. Responses were seen in both CD30 (+) and (-) pts, as well as in 4 pts who received prior CAR-T. Summary/Conclusion: This novel triplet regimen appears active in R/R DLBCL with an acceptable safety profile. The randomized portion of the study is currently enrolling.

Alliance A059102: A randomized phase II U.S. intergroup study of CHO(E)P versus CC-486-CHO(E)P versus duvelisib-CHO(E)P in previously untreated, CD30-negative, peripheral T-cell lymphomas.

TPS7593 Background: While PTCL is treated for curative intent, 5-year (yr) overall survival (OS) remains 20-25% with CHOP based therapy. For pts &lt;60 yrs old, the addition of etoposide to CHOP has been associated with improved outcomes. Brentuximab vedotin in combination with chemotherapy demonstrated an OS benefit in PTCL with CD30 &gt;10% by immunohistochemistry, and most significantly improved outcomes in anaplastic large cell lymphoma. This served as proof of principle that biomarker driven therapy can lead to improved outcomes in this rare disease (Horwitz et al Lancet 2019). Duvelisib is a gamma delta PI3 kinase inhibitor with a 50% overall response rate in PTCL and a trend toward a higher response rate in PTCL with a T-follicular helper (TFH) phenotype (Brammer et al. Blood 2021). Azacitidine is a hypomethylating agent that has shown a 75% overall response rate (ORR) in PTCL with TFH phenotype. CC-486, oral azacitidine, has been safely combined with CHOP and showed a 75% ORR with a higher ORR in PTCL with TFH phenotype (Ruan et al. Blood 2021). Methods: A051902 is a 3 arm randomized phase II US intergroup study in previously untreated PTCL with CD30 expression &lt;10% comparing standard chemotherapy (CHOP or CHOEP) to CHOP/CHOEP with duvelisib 25mg PO BID or CHOP/CHOEP with azacitidine 300mg PO. Pts will be stratified by age (&gt;60, ≤60) and TFH phenotype. Pts over age 60 will receive CHOP and those ≤60 will receive CHOEP. Prior to the randomized study, there is a safety lead-in study for the first 12 pts combining duvelisib 15mg BID with CHOP/CHOEP. The primary endpoint of the phase II study is complete remission (CR) rate by the Lugano 2014 criteria. The phase II study is powered for a 25% improvement in CR rate (45% vs 70%) in an experimental arm compared to CHOP/CHOEP with a 90% power and type I error rate of 10%. The phase II will enroll 159 pts (53 per arm). Key eligibility: 1. untreated PTCL (nodal T-cell lymphoma with TFH phenotype, follicular T-cell lymphoma, PTCL-NOS, angioimmunoblastic T-cell lymphoma, enteropathy associated T-cell lymphoma, monomorphic epitheliotropic intestinal T-cell lymphoma) with CD30 expression &lt;10%, 2. Stage I-IV, PS 0-2. Pts with transformed mycosis fungoides or anaplastic large cell lymphoma are excluded. Standard CHOP and CHOEP are administered every 21 days with growth factor support. Azacitadine 300mg will be taken on days -6 to -1 prior to cycle 1 and then on days 8 to 21 for cycles 1-5. Duvelisib 25mg BID will be taken continuously. Correlative studies include evaluation of TFH phenotype (by immunohistochemistry, gene expression profiling and DNA sequencing) and cell free DNA evaluation to predict outcomes as well as patient reported outcomes. The study was activated 7/30/2021 and the safety lead-in portion is currently enrolling. Support: U10CA180821, U10CA180882. Clinical trial information: NCT04803201.

Brentuximab vedotin in combination with lenalidomide and rituximab in patients with relapsed/refractory diffuse large B-cell lymphoma: Safety and efficacy results from the safety run-in period of the phase 3 ECHELON-3 study.

7559 Background: Patients (pts) with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who relapse after or are ineligible for hematopoietic stem cell transplant (HSCT) or chimeric antigen receptor T cell (CAR-T) therapy generally have poor outcomes. Preclinical data provide the rationale for combining brentuximab vedotin (BV), lenalidomide (len), and rituximab for the treatment of R/R DLBCL. BV+len showed promising clinical activity in a Phase 1 trial with a 57% overall response rate (ORR), 10.2-month median progression-free survival, and 14.3-month overall survival (Ward 2021). We report the results of the open-label safety run-in that was conducted prior to the randomized portion of the study. Methods: ECHELON-3 (NCT04404283) is a randomized, double-blind, placebo-controlled, active-comparator, multicenter Phase 3 study. Prior to randomization, an open-label safety run-in was conducted; pts received BV (1.2 mg/kg) and rituximab (375 mg/m2) both q3w, and len 20 mg qd. Pts must have received ≥2 prior lines of therapy and be previously treated with or were ineligible for HSCT or CAR-T, ECOG score ≤2, and PET-avid, bidimensional measurable disease ( &gt; 1.5 cm by CT). Pts with negligible CD30 expression ( &lt; 1%) were eligible. Response was assessed by the investigator according to the Lugano Classification Revised Staging System (Cheson 2014). Results: 10 pts with R/R DLBCL were enrolled. Median age was 70.5 years, 7 pts were male, and all had an ECOG ≤1. Median prior lines of therapy was 3 (range, 2 to 6); no pts received prior HSCT and 6 pts received prior CAR-T. At a median follow-up of 6.9 months (range, 2.3 to 14.1), the most common treatment emergent adverse events (TEAE) were fatigue (n = 5), anemia (n = 4) and constipation (n = 4). Grade ≥3 events were experienced by 8 pts, most commonly anemia and pneumonia (n = 3 each), and neutropenia and thrombocytopenia (n = 2 each). Serious adverse events were observed in 7 pts. Seven pts each had BV and rituximab dose modifications, and 6 pts had a len dose modification. The most common reasons for any dose modification were anemia (n = 3), neutropenia, peripheral neuropathy, or pneumonia (n = 2 each). 4 pts discontinued treatment due to an AE, 2 of which were treatment related (n = 1 each of Grade 2 fatigue; Grade 3 anemia). There was 1 death due to a TEAE that was not treatment related. The ORR (best response) was 70%, including 4 pts with a complete metabolic response, 2 pts with a partial metabolic response, and 3 pts with progressive disease. Responses were seen in both CD30 (+) and (-) pts, as well as in 4 pts who received prior CAR-T. Conclusions: This novel triplet regimen appears active in R/R DLBCL with an acceptable safety profile. The randomized portion of the study is currently enrolling. Clinical trial information: NCT04404283.

Durable remission for four pediatric patients with high-risk relapsed classical Hodgkin lymphoma treated with brentuximab vedotin plus gemcitabine but without autologous stem cell transplantation: A report from the Children's Oncology Group.

Patients with therapy-refractory or high-risk relapsed classical Hodgkin lymphoma are typically treated with the high-dose chemotherapy and autologous stem cell transplantation (HDC/ASCT) to consolidate the response to salvage therapy. The combination of brentuximab vedotin with gemcitabine has recently been shown to be an effective and safe salvage regimen. While the majority of patients with complete responses to this regimen ultimately underwent HDC/ASCT consolidation, four subjects, reported herein, achieved durable complete remissions lasting more than 4years after the study treatment but without ASCT consolidation. Further investigation of treatment strategies incorporating targeted agents may allow omission of HDC/ASCT for select patients.

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

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

Brentuximab vedotin in combination with bendamustine in pediatric patients or young adults with relapsed or refractory Hodgkin lymphoma.

Although children and young adults with Hodgkin's lymphoma usually have a favorable prognosis, patients with primary refractory disease and some subsets of relapsed patients still have a dismal outcome. Brentuximab vedotin (BV) in combination with bendamustine may represent a suitable salvage therapy; data on 32 patients aged less than 25years were retrospectively analyzed. Patients received up to six cycles of treatment of BV 1.8mg/kg on day 1 and bendamustine 90-120mg/m2 on days 2 and 3. At the end of treatment, the overall response rate was 81%. The 3-year overall and progression-free survivals are 78.1% and 67%, respectively.

The clinical and economic burden of peripheral T-cell lymphoma: a systematic literature review.

Aim: To understand the burden of treatment-naive peripheral T-cell lymphoma (PTCL). Methods: A systematic literature review was conducted in November 2020 following best practice methodology. Results: Fifty-five clinical studies were included, mostly investigatingcyclophosphamide, doxorubicin, vincristine andprednisone(CHOP)or 'CHOP-like'regimens, with combination regimens showing similar effectiveness to CHOP alone. Aside from thecombination of brentuximab vedotin + cyclophosphamide, doxorubicinand prednisone (A+CHP), other available treatments showed no statistically significant benefit over CHOP in terms of overall or progression-free survival in overall PTCL patients. The mean monthly cost per patient in the USA ranged from 6328 to US$9356 based on six studies. One economic evaluation demonstrated A+CHP to be a more cost-effective treatment option thanCHOP. Conclusion: Further research is needed to understand the humanistic and cost impact of frontline treatment for PTCL and its specific subtypes.

Pulmonary Toxicity of Hodgkin Lymphoma Treatment: A Prospective Single-Center Study.

BackgroundStandard bleomycin-containing first-line therapy and/or irradiation may cause pulmonary toxicity in Hodgkin lymphoma (HL) patients. Our aim was to prospectively assess effects of chest irradiation, bleomycin administration, and other factors on lung function in the treatment of patients with HL.MethodsPulmonary function of newly diagnosed HL patients was assessed via a St. George Respiratory Questionnaire, dynamic inhalation lung scintigraphy, spirometry, and an assessment of the diffusion capacity of the lung for carbon monoxide (DLCO) before, during, and after treatment.ResultsThis prospective study was conducted at the University of Debrecen. The study included 84 patients with classical HL. Most patients received standard doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy. Both intramuscular and intravenous administrations of bleomycin were used. Brentuximab vedotin combination chemotherapy was administered to 12 patients. Mediastinal involved-field irradiation therapy (IFRT) was used to treat 16 patients. Lung scintigraphy revealed pulmonary toxicity more sensitively than DLCO. Intravenous bleomycin administration decreased diethylenetriamine pentaacetic acid clearance. Intramuscular bleomycin had the lowest level of pulmonary toxicity among considered treatments. Currently used, mediastinal IFRT had a lower level of pulmonary toxicity than bleomycin. The current prospective evaluation confirmed previous results that determined that cumulative bleomycin dose and administration are major risk factors for pulmonary toxicity, while the currently used treatment method, mediastinal irradiation, was determined to be relatively safe for treating for HL patients.ConclusionWe agree with decreasing bleomycin dosage and number of cycles administered and we do not recommend avoiding mediastinal IFRT, unless multiple pulmonary risk factors are present.

Brentuximab Vedotin in Combination with Nivolumab, Doxorubicin, and Dacarbazine in Newly Diagnosed Patients with Advanced Stage Hodgkin Lymphoma (SGN35-027, Trial in Progress)

Brentuximab Vedotin in Combination with Nivolumab, Doxorubicin, and Dacarbazine in Newly Diagnosed Patients with Advanced Stage Hodgkin Lymphoma (SGN35-027, Trial in Progress)

Brentuximab Vedotin and Bendamustine Produce Long-Term Clinical Benefit in Patients With Relapsed or Refractory Classical Hodgkin Lymphoma: A Multicenter Real-Life Experience

BackgroundPatients with relapsed or refractory classical Hodgkin lymphoma (R/R cHL) have limited opportunities for curative therapy. High-dose therapy followed by autologous stem cell transplantation (HDT-ASCT) produces cure rates of 50% to 60%. Patients relapsing after, or ineligible for HDT-ASCT have limited therapeutic options and long-term remission is uncommon. Furthermore, few patients are candidate to allogeneic stem cell transplantation (AlSCT), a potentially curative approach. The combination of brentuximab vedotin and bendamustine (BVB) is a promising treatment for patients with R/R cHL, regardless of SCT eligibility. Patients and methodsWe conducted a real-life study of BVB in 41 patients with R/R cHL after failure of ≥ 1 therapy including ASCT, AlSCT, or BV. ResultsAmong 40 patients evaluable for efficacy, the overall response rate and complete response (CR) rate were 75% and 50%, respectively. No significant differences were observed between patients with primary refractory and relapsed disease, previously treated with ≤ 2 and ≥ 3 lines of therapy, or BV-exposed and BV-naïve. After a median follow-up of 38 months, the median progression free survival (PFS) for the entire population is 26 months; PFS is not reached, 10.5 months, and 4 months for patients achieving CR, partial response and no response, respectively (P < .0001). BVB was well tolerated and no grade 4 toxicity or new safety signals were observed. The most common treatment-emergent adverse events were infections. ConclusionOur experience supports the efficacy and tolerability of the BVB combination in R/R cHL as a bridge to SCT, or as a definitive therapy for SCT-ineligible patients. Larger comparative studies testing BVB against standards of care are warranted in both settings.

Combination brentuximab vedotin and bendamustine for pediatric patients with relapsed/refractory Hodgkin lymphoma

AbstractIn patients with relapsed/refractory (R/R) Hodgkin lymphoma (HL), achieving a complete metabolic response (CMR) after salvage therapy is associated with superior outcomes, and optimal treatments must be identified. The combination of brentuximab vedotin and bendamustine (BVB), although highly active in adult patients, has not been extensively evaluated in pediatric patients with R/R HL. We performed a multicenter, retrospective review of pediatric patients <21 years of age with R/R HL treated with BVB from January 2016 through July 2019. Response was assessed by local radiologists according to Lugano classification criteria. Twenty-nine patients (17 relapsed, 12 refractory) with a median age of 16 years (range, 10-20) were treated with BVB and received a median of 3 cycles of therapy (range, 2-7). Patients received an infusion of 1.8 mg/kg of BV on day 1 with bendamustine 90 mg/m2 on days 1 and 2 of 3-week cycles. Nineteen patients (66%) achieved a CMR (95% CI, 46-82). An objective response was observed in 23 patients (objective response rate, 79%; 95% CI, 60-92). The most common grade 3 and 4 toxicities were hematologic, and 3 patients (10%) experienced grade 3 infusion reactions. Seventeen of 18 patients underwent successful mobilization and collection of stem cells. Sixteen patients (13 autologous, 3 allogeneic) received a consolidative transplant after BVB. The 3-year post-BVB event-free and overall survival were 65% (95% CI, 46-85) and 89% (95% CI, 74-100), respectively. For pediatric patients with R/R HL, BVB was well tolerated and compared favorably with currently accepted salvage regimens.

Five-Year Survival Results: Frontline Brentuximab Vedotin in Combination with CHP in Patients with CD30-Expressing Peripheral T-Cell Lymphomas

Five-Year Survival Results: Frontline Brentuximab Vedotin in Combination with CHP in Patients with CD30-Expressing Peripheral T-Cell Lymphomas

Brentuximab Vedotin Plus Bendamustine Is an Effective Salvage Regimen for Pediatric Patients with Relapsed Hodgkin Lymphoma

Background :Pediatric patients with relapsed/refractory Hodgkin Lymphoma have superior outcomes when achieving a complete remission prior to autologous stem cell transplant (ASCT). Optimal salvage regimens need to be identified as current approaches result in complete responses (CR) in approximately 25-35% of patients. The combination of brentuximab vedotin and bendamustine is highly active in adult patients with relapsed/refractory Hodgkin Lymphoma, but has not been evaluated in the pediatric population. We report our preliminary experience regarding the safety and efficacy of brentuximab vedotin and bendamustine prior to stem cell transplant (SCT) in pediatric patients treated for relapsed Hodgkin lymphoma at a single center.Methods:We performed a retrospective review of pediatric patients with relapsed Hodgkin lymphoma treated with brentuximab vedotin and bendamustine between April 2016 to July 2017. Patients received an infusion of 1.8mg/kg of brentuximab vedotin on Day 1 with bendamustine 90mg/m2 on Days 1 and 2 of 3-week cycles. Response assessment was performed and repeated following 2-3 cycles of therapy. Patients went on to SCT after achieving a CR or best response at the discretion of the treating physicians. Patients resumed post-transplant treatment with brentuximab vedotin as monotherapy for up to 16 doses.Results:Five patients (1 female, 4 males) with a median age of 16.5 years at the time of relapse (range, 12.2 -17.9 years) were treated with the combination of brentuximab/bendamustine. Four patients were in first relapse and 1 was treated in second relapse nine months following a prior ASCT. Patients received a median of 5 cycles of therapy (range 2-5 cycles), with 2 patients receiving an additional cycle of brentuximab monotherapy prior to proceeding to SCT. The main toxicity observed was infusion-related reactions, with 2 patients experiencing anaphylaxis. These individuals were able to continue planned therapy following desensitization against brentuximab. All patients were in complete remission by PET prior to SCT. Four patients underwent successful stem cell mobilization and collection. The individual treated following second relapse received an allogeneic transplant from a matched unrelated donor. All patients are alive with no evidence of disease a median of 11.3 months since beginning salvage therapy (range 1.2-15 months). Four patients are a median of 6.5 months (range 4-11 months) post-SCT and continue on brentuximab monotherapy, with 1 individual currently awaiting ASCT.Conclusions :Combination therapy with brentuximab vedotin and bendamustine was highly active in pediatric patients with relapsed Hodgkin lymphoma and would compare favorably with currently accepted salvage regimens. Incidence of infusion-related reactions can be minimized through the use of adequate premedication. These results support further evaluation of this regimen in the context of a multicenter prospective clinical trial. DisclosuresCurran:Novartis: Consultancy; Juno Therapeutics: Research Funding. Kernan:Gentium: Other: NAK received grants from Gentium during the conduct of the study, and her research was supported by The National Cancer Institute of the National Institutes of Health under award number P30 CA008748; the content is solely the responsibility of the author .