scholarly journals Relabáló/refrakter Hodgkin-lymphoma brentuximab vedotin kezelése. Hazai tapasztalatok

2017 ◽  
Vol 158 (41) ◽  
pp. 1630-1634
Author(s):  
Zsuzsa Molnár ◽  
László Imre Pinczés ◽  
Klára Piukovics ◽  
Ildikó Istenes ◽  
Krisztina Wolf ◽  
...  
Keyword(s):  
Survival Rate ◽  
Complete Remission ◽  
Hodgkin Lymphoma ◽  
Remission Rate ◽  
Single Agent ◽  
Brentuximab Vedotin ◽  
Common Symptom ◽  
Antibody Drug Conjugate ◽  
Hematopoietic Stem ◽  
Refractory Hodgkin Lymphoma

Abstract: Introduction: The treatment of relapsed or refractory Hodgkin lymphoma is still a major therapeutic challenge. The use of brentuximab vedotin, an anti-CD30 antibody-drug conjugate, represents a promising approach for these patients, however clinical outcomes have not yet been evaluated in Hungary. Aim: Our aim was to assess the efficacy, safety and outcome of brentuximab vedotin treatment in Hungarian Hodgkin lymphoma patients. Method: In this retrospective case note review we enrolled patients at 6 clinical sites countrywide who were diagnosed with Hodgkin lymphoma and received brentuximab vedotin between 1 January 2013 and 31 December 2016. Results: A total of 86 patients were treated with brentuximab vedotin during the examined period. Before therapy initiation 66% of our patients had advanced-stage disease. Overall response rate to brentuximab vedotin, administered before autologous hematopoietic stem cell transplantation (n = 54) was 66.6%, complete remission rate was 42.6%. Thirty patients received brentuximab vedotin after AHSCT, 46.67% responded to treatment, 30% achieved complete remission. Thirty-six patients received the drug as a single-agent therapy, 50 patients were given brentuximab vedotin in combination, 39 of them with bendamustin. Toxicity was observed only in 13.95% of our patients, most common symptom was skin rash. Based on our analysis the estimated 5-year overall survival rate was 78.7%, the estimated progression free survival rate was 23.59 months (95% CI: 19.50–27.68). Conclusion: Brentuximab vedotin carries a substantial improvement in the treatment of relapsed or refractory Hodgkin lymphoma. Our results underline prior observations published in the literature. The use of brentuximab vedotin in combination can be beneficial, however further investigation is needed on the subject. Orv Hetil. 2017; 158(41): 1630–1634.

scholarly journals Successful rapid desensitization to the antibody–drug conjugate brentuximab vedotin in a patient with refractory Hodgkin lymphoma

2015 ◽  
Vol 22 (1) ◽  
pp. 188-192 ◽  
Author(s):  
Marie Fizesan ◽  
Christopher Boin ◽  
Olivier Aujoulat ◽  
Georges Newinger ◽  
Dana Ghergus ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Brentuximab Vedotin ◽  
Antibody Drug Conjugate ◽  
Drug Conjugate ◽  
Refractory Hodgkin Lymphoma ◽  
Antibody Drug

scholarly journals Safety and Efficacy of Allogeneic Stem Cell Transplantation after PD-1 Blockade for Patients with Relapsed/Refractory Classical Hodgkin Lymphoma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1561-1561 ◽  
Author(s):  
Anastasiya V Beynarovich ◽  
Kirill Lepik ◽  
Nataliia Mikhailova ◽  
Elena Kondakova ◽  
Yuri Zalaylov ◽  
...  
Keyword(s):  
Adverse Events ◽  
Hodgkin Lymphoma ◽  
Immune Checkpoint ◽  
Chronic Gvhd ◽  
Single Agent ◽  
Conditioning Regimen ◽  
Successful Outcome ◽  
Sinusoidal Obstruction Syndrome ◽  
Hematopoietic Stem ◽  
Refractory Hodgkin Lymphoma

Introduction: The programmed-death 1 blockade with nivolumab demonstrated high efficiency in patients with relapsed and refractory Hodgkin lymphoma (rrHL) with acceptable toxicity profile. However, most of the patients treated with immune checkpoint inhibitor (CPIs) will eventually progress on this therapy. Allogeneic hematopoietic stem cells transplantation (allo-HSCT) is a potentially curative option for patients with rrHL. Therefore, allo-HSCT is a consideration for selected patients with HL after treatment with CPIs. There are concerns that CPIs before allo- HSCT may increase the incidence of graft-versus-host disease, immune-related adverse events, and nonrelapse mortality (NRM). At present, there is no consensus regarding the optimal transplant strategy for patients previously treated with immune checkpoint blockade. The aim of this study was to evaluate outcomes in patients with rrHL who received CPIs as a bridge to allo-HSCT. Patients and methods: We retrospectively evaluated the results of allo-HSCT in 22 patients who had been transplanted after prior PD-1 blockade between 2017 and 2019 at the R. Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantology at the First St. Petersburg State Pavlov Medical University (CIC 725). All patients received reduced-intensity conditioning regimen (fludarabine 30 mg/m2, bendamustine 130 mg /m2 per day for 3 days (FluBe)) and post-transplant cyclophosphamide-based GvHD prophylaxis (PTCy). Patients received immune checkpoint inhibitors before allo-HSCT as a single-agent nivolumab or in combination with brentuximab vedotin or chemotherapy. The best response to PD-1 therapy was a complete response (CR) in 9 patients, partial response in 5 patients, 5 patients received transplant during the disease progression and 3 patients were transplanted in indetermined response according to the LYRIC. Patients received a median of 20 (range, 6-32) cycles of a PD-1 inhibitor. The median time from the last dose of anti-PD-1 therapy to HSCT was 83 days (range, 50-350). Results: At the time of analysis, median follow-up was 14 months (range, 1-26 months). Ninety one percent of patients engrafted. One patient had primary graft failure and one died on the day of the haploidentical graft transfusion due to cytokine release syndrome. The 1-year OS and EFS were 91% and 78% respectively, whereas the 1-year cumulative incidences of relapse and NRM were 9% and 9% respectively.Two patients with relapse after allo-HSCT were treated with donor lymphocyte infusion (DLI) in combination with chemotherapy. Both patients remain alive. 4/20 of the engrafted patients developed grade 2 GvHD and all responded to steroids. 4/20 patients developed severe grade 3-4 GvHD and only 1 patient responded to steroids. The cumulative incidence of chronic GVHD (cGVHD) was 35%, including 3 patients with severe, steroid-refractory cGVHD. There were no other immune-related adverse events. No cases sinusoidal obstruction syndrome was observed Conclusions: Our study demonstrates that HSCT after PD-1 blockade is feasible and not associated with higher mortality. We suggest that prior PD-1 blockade should not be considered a contraindication to HSCT in patients with relapsed and refractory Hodgkin lymphoma. severe The rate of severe acute and chronic GvHD was relatively higher than previously reported for PTCy-based prophylaxis, but was manageable in the majority of cases. The time between anti-PD-1 therapy and allo-HSCT and PTCy is likely to be important in the successful outcome of the transplant. Disclosures Moiseev: Novartis: Consultancy, Honoraria, Other: Travel grants, Speakers Bureau; MSD: Other: Travel grants; Celgene: Consultancy, Other: Travel grants; Takeda: Other: Travel grants; Pfizer: Other: Travel grants; BMS: Other: Travel grants.

scholarly journals Brentuximab Vedotin Treatment for Primary Refractory Hodgkin Lymphoma

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Hung-Bo Wu ◽  
Shyh-An Yeh ◽  
Huei-Yung Chen
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Hodgkin Lymphoma ◽  
Cell Transplantation ◽  
Mediastinal Tumor ◽  
Remission Rate ◽  
Brentuximab Vedotin ◽  
Current Standard ◽  
Local Progression ◽  
Refractory Hodgkin Lymphoma

Up to 40% of patients with advanced Hodgkin lymphoma (HL) become refractory or relapsed after current standard chemotherapy, among which primary refractory HL confers a particularly poor outcome. With intensive salvage chemotherapy and autologous stem cell transplantation, the long-term remission rate for these patients was only 30%, but more selective treatments with higher therapeutic index are needed. We report the experience of using a new anti-CD30 immunotoxin, brentuximab vedotin, in salvage treatment of a 30-year-old woman with primary refractory Hodgkin lymphoma. The patient presented with SVC syndrome due to the bulky mediastinal tumor and was confirmed to have classical Hodgkin lymphoma, nodular sclerosis type, stage IIIA. The tumor responded to induction chemotherapy transiently, but local progression was noted during subsequent cycles of treatment. Salvage radiotherapy to the mediastinal tumor, obtained no remission but was followed by rapid in-field progression and then lung metastasis. She declined stem cell transplantation and received salvage brentuximab vedotin (BV) therapy, which induced dramatic shrinkage of tumor without significant side effects. Serial followup of PET/CT imaging confirmed a rapid and continuous complete remission for 12 months. Although durability of the remission needs further observation, this case illustrates the excellent efficacy of brentuximab vedotin in primary refractory Hodgkin lymphoma.

Activity of the Investigational Antibody–Drug Conjugate Brentuximab Vedotin (SGN-35) in Patients with Relapsed or Refractory Hodgkin Lymphoma or Systemic Anaplastic Large-Cell Lymphoma: Comparisons with Meta-Analyses of Historical Control Chemotherapy Data

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4975-4975
Author(s):  
Antonio Gualberto ◽  
Andy Chi ◽  
Yi Liu
Keyword(s):  
Hodgkin Lymphoma ◽  
Anaplastic Large Cell Lymphoma ◽  
Cell Lymphoma ◽  
Meta Analysis ◽  
Large Cell ◽  
Brentuximab Vedotin ◽  
Antibody Drug Conjugate ◽  
Large Cell Lymphoma ◽  
Meta Analyses ◽  
Refractory Hodgkin Lymphoma

Abstract Abstract 4975 Background: Brentuximab vedotin (SGN-35) is an investigational CD30-directed antibody–drug conjugate consisting of the monoclonal chimeric antibody cAC10 specific for human CD30, the potent antimicrotubule agent monomethyl auristatin E (MMAE), and a protease-cleavable linker that covalently attaches cAC10 to MMAE. Two single-arm pivotal phase 2 trials in relapsed or refractory Hodgkin lymphoma (HL; SG035-0003, Younes et al, ICML 2011) and systemic anaplastic large-cell lymphoma (sALCL; SG035-0004, Shustov et al, ICML 2011) have shown brentuximab vedotin (1.8 mg/kg IV every 3 weeks for up to 16 cycles) to have durable antitumor activity in terms of overall response rate and complete remission (CR) rate with a manageable safety profile. In the absence of a suitable comparator regimen for the conduct of these trials, and per the ICH E10 (CHMP/ICH/364/96) guideline, we conducted meta-analyses of historical chemotherapy data to compare the activity of brentuximab vedotin in the pivotal single-arm trials to the activity of other therapies used for the treatment of relapsed or refractory HL and sALCL. Methods: CR rate was the endpoint since in both HL and aggressive non-Hodgkin's lymphoma (NHL), achievement of CR has been shown to correlate with long-term clinical benefit (Josting & Schmitz, 2004; Lee et al, Ann Oncol 2011). For the HL meta-analysis, a PubMed search identified all prospective trials and retrospective case series in which ≥10 adult HL patients with relapsed or refractory disease were treated with gemcitabine alone or in combination; these regimens were selected for the control population because they constitute one of the most commonly used systemic therapies beyond second-line treatment in HL. Trials were classified as post-autologous stem cell transplant (ASCT; ≥33% of enrolled patients), or ASCT-naïve. For the sALCL meta-analysis, a PubMed search identified all trials since 2001 of aggressive relapsed or refractory NHL that included at least one sALCL patient. Due to the rarity of relapsed or refractory sALCL and the absence of standard therapy in this setting, no specific regimen was selected as a control. Quantitative statistical meta-analyses were carried out per pre-specified plans to minimize bias and ensure integrity of the statistical analysis, and performed using random effect models; estimates (95% CI) of overall CR rate were provided. Results: For the HL meta-analysis, 16 trials with 605 patients were identified, including nine post-ASCT trials (n=296, median of three prior regimens) in which a median of 44% (range 33–64%) of patients had prior ASCT, and seven ASCT-naïve trials (n=309, median of one prior regimen). CR rates are shown in the figure. The estimated overall CR rate in the post-ASCT subgroup was 15% (95% CI: 6.5, 23.5), which was significantly lower than the CR rate of 34% (95% CI: 25.2, 44.4; p=0.003) seen with brentuximab vedotin in SG035-0003, in which all patients had prior ASCT and the median number of prior regimens was 3.5. In the ASCT-naïve subgroup, the estimated overall CR rate was 35% (95% CI: 16.9, 52.2), which was not significantly different versus SG035-0003. However, patients in the historical ASCT-naïve subgroup had less advanced disease and were less heavily pretreated. Considering all trials, the estimated overall CR rate was 24% (95% CI: 14.2, 33.9), with a trend towards lower activity versus SG035-0003 (p=0.148). For the sALCL meta-analysis, 19 trials with 817 NHL patients (median of two prior regimens) were identified, which included 1.6–20.8% sALCL patients (n=48 in total). The estimated overall CR rate of 18% (95% CI: 11.3, 24.5) was significantly lower than with brentuximab vedotin in SG035-0004 (53% [95% CI: 39.9, 66.7], p<0.0001). Conclusions: The anti-tumor activity of brentuximab vedotin in relapsed or refractory post-ASCT HL patients, in terms of CR rate, appears to exceed that of gemcitabine-based therapies in this setting, and appears comparable to that seen with combination chemotherapy in ASCT-naïve patients with less advanced disease. The anti-tumor activity of brentuximab vedotin also appears to exceed that of other treatment options for aggressive relapsed or refractory NHL, including sALCL. Acknowledging the limitations of these comparisons, these meta-analyses suggest that brentuximab vedotin may provide meaningful long-term clinical benefit in relapsed or refractory HL and sALCL. Disclosures: Gualberto: Millennium Pharmaceuticals, Inc.: Employment. Off Label Use: Brentuximab vedotin for the treatment of relapsed or refractory Hodgkin lymphoma and systemic anaplastic large-cell lymphoma. Chi:Millennium Pharmaceuticals, Inc.: Employment. Liu:Millennium Pharmaceuticals, Inc.: Employment.

Frontline brentuximab vedotin in Hodgkin lymphoma and CD30-expressing peripheral T-cell lymphoma for older patients and those with comorbidities.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS8069-TPS8069
Author(s):  
Christopher A. Yasenchak ◽  
Rodolfo Eduardo Bordoni ◽  
Victor Y. Yazbeck ◽  
Dipti Patel-Donnelly ◽  
Tim Larson ◽  
...  
Keyword(s):  
T Cell ◽  
Complete Remission ◽  
Hodgkin Lymphoma ◽  
Older Patients ◽  
Cell Lymphoma ◽  
Single Agent ◽  
Brentuximab Vedotin ◽  
T Cell Lymphoma ◽  
Peripheral T Cell Lymphoma ◽  
Younger Patients

TPS8069 Background: Older patients and those with significant comorbidities have not attained outcomes seen in younger patients with classical Hodgkin lymphoma (cHL) and CD30-expressing peripheral T-cell lymphoma (PTCL). Five-year progression-free survival (PFS) was 30%–45% in older HL patients treated with combination chemotherapy versus 75%–80% in younger patients (Evens 2008; Proctor 2009). Similarly, when adjusted for age, a Charleston Comorbidity Index ≥2 was independently associated with worse overall survival (HR=1.63) and PFS (HR=1.54) (Ellin 2018). Brentuximab vedotin (BV, ADCETRIS), a CD30-directed antibody-drug conjugate, has robust activity in cHL patients refractory to several lines of chemotherapy. BV monotherapy in 27 cHL patients aged ≥60 years had a 92% objective response rate (ORR) and 73% achieved complete remission (Forero-Torres, 2015). BV was also active and well-tolerated in CD30-expressing PTCL patients with relapsed or refractory disease (Horwitz 2014). Frontline BV monotherapy may have the potential to be an active and well-tolerated treatment for cHL and PTCL patients who are older or have significant comorbidities, which are populations with high unmet need. Methods: This phase II, open-label study, SGN35-015 (NCT01716806), has added 2 cohorts to evaluate the efficacy and tolerability of BV monotherapy in treatment naive patients with cHL, (Part E), or CD30-expressing PTCL (Part F, n~50 each) who are unsuitable for conventional combination therapy due to comorbidity-related factors as determined by a Cumulative Illness Rating Scale (CIRS) score ≥10 or dependence on others for any instrumental activities of daily living. Eligible patients must also have an Eastern Cooperative Oncology Group (ECOG) performance status ≤3 and measurable disease ≥1.5 cm per radiographic techniques. BV (1.8 mg/kg) will be administered as a single intravenous infusion on day 1 of each 2-day cycle. Patients achieving a complete remission, partial remission, or stable disease will receive up to 16 cycles of treatment. Response will be assessed by blinded independent central review of spiral CT and PET scans at Cycles 2, 6, 11, and at end of treatment to be graded per Lugano 2014. The primary objective of these cohorts is to assess ORR of frontline therapy with single-agent BV in patients who have significant comorbidities. Clinical trial information: NCT01716806 .

Excellent Outcome for Pediatric Patients With High-Risk Hodgkin Lymphoma Treated With Brentuximab Vedotin and Risk-Adapted Residual Node Radiation

2021 ◽  
pp. JCO.20.03286
Author(s):  
Monika L. Metzger ◽  
Michael P. Link ◽  
Amy L. Billett ◽  
Jamie Flerlage ◽  
John T. Lucas ◽  
...  
Keyword(s):  
High Risk ◽  
Complete Remission ◽  
Hodgkin Lymphoma ◽  
Response Assessment ◽  
Complete Response ◽  
Brentuximab Vedotin ◽  
Antibody Drug Conjugate ◽  
Open Label ◽  
Unexpected Death ◽  
Excellent Outcome

PURPOSE Brentuximab vedotin, an effective anti-CD30 antibody-drug conjugate approved for use in adults with classical Hodgkin lymphoma (HL), was introduced in this frontline trial to reduce prescribed radiation in children and adolescents with classical HL. METHODS Open-label, single-arm, multicenter trial for patients (age ≤ 18 years) with stage IIB, IIIB, or IV classical HL was conducted. Brentuximab vedotin replaced each vincristine in the OEPA/COPDac (vincristine, etoposide, prednisone, and doxorubicin/cyclophosphamide, vincristine, prednisone, and dacarbazine) regimen according to GPOH-HD2002 treatment group 3 (TG3); two cycles of AEPA and four cycles of CAPDac. Residual node radiotherapy (25.5 Gy) was given at the end of all chemotherapy only to nodal sites that did not achieve a complete response (CR) at the early response assessment (ERA) after two cycles of therapy. Primary objectives were to evaluate the safety and efficacy (complete remission at ERA) of this combination and the 3-year event-free (EFS) and overall survival (OS). The trials are registered at ClinicalTrials.gov identifier: NCT01920932 . RESULTS Of the 77 patients enrolled in the study, 27 (35%) achieved complete remission at ERA and were spared radiation. Patients who were irradiated received radiation to individual residual nodal tissue. At a median follow-up of 3.4 years, the 3-year EFS was 97.4% (SE 2.3%) and the OS was 98.7% (SE 1.6%). One irradiated patient experienced disease progression at the end of therapy and now remains disease free more than 6 years following salvage therapy, and one unexpected death occurred. Only 4% of patients experienced grade 3 neuropathy. CONCLUSION The integration of brentuximab vedotin in the frontline treatment of pediatric high-risk HL is highly tolerable, facilitated significant reduction in radiation exposure, and yielded excellent outcomes.

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