scholarly journals A Pilot Trial of Adriamycin, Pembrolizumab, Vinblastine and Dacarbazine (APVD) for Patients with Untreated Classical Hodgkin Lymphoma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5299-5299
Author(s):  
Ryan C. Lynch ◽  
Chaitra S. Ujjani ◽  
Edus H. Warren ◽  
David M. Kurtz ◽  
Hilary Coye ◽  
...  
Keyword(s):  
Adverse Events ◽  
Hodgkin Lymphoma ◽  
Research Funding ◽  
Metabolic Response ◽  
Brentuximab Vedotin ◽  
T Cell Subsets ◽  
Advanced Stage ◽  
Classical Hodgkin Lymphoma ◽  
Complete Metabolic Response ◽  
Dose Delay

Background: ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) forms the backbone of frontline management of classical Hodgkin lymphoma (CHL) in North America regardless of stage. Expected cure rates with upfront therapy approach 75% in advanced stage, and 85-90% in early stage. A novel regimen incorporating brentuximab vedotin sought to improve upon ABVD in untreated advanced stage CHL patients (brentuximab vedotin + AVD). While it demonstrated a modest modified PFS benefit, it was associated with notable toxicities including higher rates of neuropathy and infection. PD-1 inhibition is highly effective in relapsed/refractory CHL, leading to the FDA approval of nivolumab and pembrolizumab in this setting. The first-line setting may represent the ideal time for a PD-1 inhibitor, with relatively intact host immunity and coexistence of malignant cells and T-cells in the microenvironment. Using a proven chemotherapy backbone, we designed a trial adding pembrolizumab to AVD chemotherapy (APVD) without a PD-1 inhibitor lead-in for untreated CHL (NCT03331341). Methods: This is a single arm pilot study combining pembrolizumab with AVD in untreated CHL of any stage. Eligibility requires ECOG 0-1, adequate organ function, and measurable disease. The trial intends to enroll 30 patients. AVD is given at standard doses on days 1 and 15 of a 28-day cycle. Pembrolizumab (200 mg IV) is given starting cycle 1 day 1 and every 21 days thereafter (cycle 1 day 22, cycle 2 day 15 etc.). The primary objective is to estimate the safety of delivering 2 cycles of APVD. The study will be determined a success if > 85% of subjects are able to complete 2 cycles of therapy without a dose delay > 3 weeks. Operationally, the stopping rule will be activated if the lower limit of the 95% confidence interval of toxicity crosses 15%. Thus, the trial would stop if 4/10, 7/20, 8/25, or 9/30 had a dose delay of >3 weeks due to toxicity. The secondary objective is to estimate the FDG-PET2 negative (Deauville score 1-3) after 2 cycles of APVD. Exploratory objectives include overall and progression free survival, predictive capacity of PET2 after APVD, peripheral blood flow cytometry of T-cell subsets, and analysis of ctDNA. After PET2 response assessment, subjects may continue APVD for up to 6 total cycles, or pursue treatment deemed appropriate for their stage/risk factors (including alternate systemic therapy or radiotherapy) at investigator discretion. Results: Six subjects have enrolled and received 2 cycles of therapy. Median age of these subjects was 28 years (range 18-69). Most subjects have advanced stage (stage II n=1 (17%), stage III n=3 (50%), stage IV n=2, (33%)). 3/6 (50%) of subjects had B symptoms at diagnosis, while 1/6 (17%) had bulky disease. Among the 6 subjects enrolled thus far, all have completed the first 2 cycles of therapy without any treatment delays. 3/6 subjects achieved a complete metabolic response (Deauville 1-3) on PET2, and 3/6 had a partial response (PR) with Deauville 4. The only subject who has completed all 6 cycle of therapy had a PET2 with Deauville 4 which converted to Deauville 2 upon completion of all therapy. There were no grade 2+ AEs attributable to pembrolizumab. No serious AEs have been reported. Non-hematologic grade 1 AEs of note include fatigue (50%), AST/ALT increase (33%), nausea (33%), arthralgia (17%), diarrhea (17%), maculopapular rash (17%), fever (17%), and alkaline phosphatase increased (17%). Conclusion: The concurrent combination of pembrolizumab with AVD chemotherapy for untreated CHL has been safe to date without any dose delays, serious adverse events, or immune-related adverse events of grade 2 or higher. All patients treated thus far achieved an objective response by PET2, with 3/6 achieving a complete metabolic response by interim scan. One subject has completed all therapy with a complete metabolic response (Deauville 2) after PET2 showed Deauville 4. Trial enrollment is ongoing. Disclosures Lynch: Incyte Corporation: Research Funding; T.G. Therapeutics: Research Funding; Johnson Graffe Keay Moniz & Wick LLP: Consultancy; Juno Therapeutics: Research Funding; Takeda Pharmaceuticals: Research Funding; Rhizen Pharmaceuticals S.A: Research Funding. Ujjani:Atara: Consultancy; Astrazeneca: Consultancy; Genentech: Honoraria; AbbVie: Honoraria, Research Funding; Gilead: Consultancy; PCYC: Research Funding; Pharmacyclics: Honoraria. Kurtz:Roche: Consultancy. Gopal:Seattle Genetics, Pfizer, Janssen, Gilead, Sanofi, Spectrum, Amgen, Aptevo, BRIM bio, Acerta, I-Mab-pharma, Takeda, Compliment, Asana Bio, and Incyte.: Consultancy; Teva, Bristol-Myers Squibb, Merck, Takeda, Seattle Genetics, Pfizer, Janssen, Takeda, and Effector: Research Funding; Seattle Genetics, Pfizer, Janssen, Gilead, Sanofi, Spectrum, Amgen, Aptevo, BRIM bio, Acerta, I-Mab-pharma, Takeda, Compliment, Asana Bio, and Incyte: Honoraria.

Brentuximab Vedotin Combined with ABVD or AVD for Patients with Newly Diagnosed Advanced Stage Hodgkin Lymphoma: Long Term Outcomes

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 292-292 ◽  
Author(s):  
Joseph M Connors ◽  
Stephen Ansell ◽  
Steven I. Park ◽  
Michelle A. Fanale ◽  
Anas Younes
Keyword(s):  
Hodgkin Lymphoma ◽  
Research Funding ◽  
Response Rate ◽  
Phase 1 ◽  
Brentuximab Vedotin ◽  
Advanced Stage ◽  
Newly Diagnosed ◽  
Genetics Research

Background: The ABVD regimen containing doxorubicin, bleomycin, vinblastine, and dacarbazine is a common standard of care for the frontline treatment of advanced stage Hodgkin lymphoma (Santoro 1987; Duggan 2003) and is curative for the majority of patients; however, up to 30% of patients require a secondary therapy. Hodgkin Reed-Sternberg cells of classical HL (cHL) typically express CD30. In a pivotal phase 2 trial brentuximab vedotin (A, ADCETRIS®), comprised of an anti-CD30 monoclonal antibody conjugated by a protease-cleavable linker to a microtubule-disrupting agent, monomethyl auristatin E (MMAE) induced an objective response rate (ORR) of 75% and complete response rate (CR) of 34% in highly treatment-refractory patients with cHL (Younes 2012). Methods: We conducted a phase 1, open-label, multicenter study to evaluate the safety and efficacy of A when administered in combination with standard therapy (ABVD) or the same regimen without bleomycin (AVD) (Younes 2013). Adult patients with newly diagnosed advanced stage (II bulky, II B, III or IV; 80% stage III or IV) received doses of 0.6, 0.9, or 1.2 mg/kg A with standard doses of ABVD or 1.2 mg/kg with AVD, depending on cohort assignment on Days 1 and 15 of each 28-day cycle for up to 6 cycles of therapy. Previously we reported that among patients assessable for response 95% of patients given ABVD+A achieved a CR, as did 96% of patients given AVD+A. None of 26 patients given AVD+A but 11 of 25 (44%) given ABVD+A experienced pulmonary toxicity, including 2 deaths, establishing that A cannot be safely combined with bleomycin. In this current study we provide the long term survival and safety data on patients enrolled in the phase 1 trial. Results: In total 51 patients were assigned to either ABVD+A (n=25) or AVD+A (n=26). 1 patient who withdrew from the trial during the first cycle of ABVD+A is excluded from this analysis and 1 patient who received 3 cycles of ABVD+A, then withdrew, then received 3 cycles of ABVD alone and 2 patients who died during treatment (pulmonary toxicity) are included (total n=50). Median follow-up from diagnosis for the 24 patients treated with ABVD+A is 41 months (range 9-51 months) and for the 26 patients treated with AVD+A, 31 months (range 9-35 months). All 26 patients treated with AVD+A have been followed longer than the longest time to relapse (7 months). 45 patients remain in first CR and 5 treatment failures have occurred: 4 in the ABVD+A cohort (2 toxic deaths; 2 relapses (9 and 23 months from diagnosis)) and 1 after AVD+A (7 months from diagnosis). 3y-failure-free survival (3y-FFS) is 83% and 96% for ABVD+A and AVD+A, respectively, and 3y-overall survival (3y-OS), is 92% and 100%. No additional toxic deaths have occurred in follow-up. Conclusions: These updated outcomes reflecting the impact of adding brentuximab vedotin (1.2 mg/kg) to standard doses of AVD for classical Hodgkin lymphoma, demonstrating 96% 3y-FFS and 100% 3y-OS with no major unexpected toxicity, strongly support the current large international trial comparing AVD-A (AVD+1.2mg/kg brentuximab vedotin) to standard ABVD (ECHELON-1, clinicaltrials.gov NCT01712490), which may identify a new, less toxic gold standard treatment for advanced stage classical Hodgkin lymphoma. Disclosures Connors: Seattle Genetics: Research Funding. Off Label Use: brentuximab vedotin in phase 1 trial. Ansell:Seattle Genetics: Research Funding. Park:Seattle Genetics: Research Funding; Millennium/Takeda: Research Funding. Fanale:Seattle Genetics: Research Funding. Younes:Seattle Genetics: Research Funding; Millennium/Takeda: Research Funding.

scholarly journals Brentuximab Vedotin Alone and in Combination with Bendamustine As Salvage Therapy for Primary Refractory or Relapsed Hodgkin Lymphoma: Multicentre Experience of the Polish Lymphoma Research Group (PLRG)

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5375-5375
Author(s):  
Anna Czyz ◽  
Anna Lojko-Dankowska ◽  
Monika Joks ◽  
Mieczyslaw Komarnicki ◽  
Monika Dlugosz-Danecka ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Salvage Therapy ◽  
Research Funding ◽  
Response Rate ◽  
Metabolic Response ◽  
Therapeutic Option ◽  
Study Groups ◽  
Brentuximab Vedotin ◽  
European Medicines Agency ◽  
Cell Transplant

Abstract An optimal treatment for patients with primary refractory or relapsed (R/R) Hodgkin lymphoma (HL) who did not respond to standard salvage therapy has not been established. Brentuximab vedotin (BV) and bendamustine (B) used as monotherapy were shown to be active in R/R HL and both are recommended as a therapeutic option. It has been proposed that the combination of BV with B (BVB) may improve the outcome of R/R HL patients. To test this hypothesis, we compared retrospectively the efficacy and safety of BV and BVB regimen in R/R HL patients. Methods: Since March 2014 all patients with R/R HL treated at PLRG centers were offered either BV in monotherapy every 21 days or in combination with B (B 90 mg/m² on days 1 and 2 of treatment cycle) according to the policy in each center. Results: BV or BVB therapy was administered to 94 patients (median age 33 years, range 18-68) with primary refractory (n=54) or relapsed HL (n=40), including 34 patients after autologous stem cell transplant (ASCT). The patients were treated with the median of 3 (range, 2-12) prior chemotherapy lines. Fifty-seven patients received BV and 37 patients BVB regimen. In 16 of them, BVB was de-escalated to BV after the median of 2 cycles (range, 2-7). The patients' and disease characteristics did not differ between two groups. In the whole study group, the median number of applied cycles per patient was 4 (range, 2-16). Dose-limiting toxicities were observed in 8% of patients. No difference was found between BV and BVB group, with similar rate of grade 3-4 neutropenia (16% vs 13%) and thrombocytopenia (4% vs 3%). Lung infection occurred in 1 patient treated with BV (2%) and 3 treated with BVB (2% vs 8%, p ns), with 2 treatment-related deaths in the BVB group. The response rate after 2 cycles of BV and BVB treatment defined as complete (CMR) or partial metabolic response (PMR) assessed by positron emission tomography was 69% (26% of CMR and 43% of PMR) and 89% (46% of CMR and 43% of PMR), respectively (p=0.036). After 4-6 cycles of treatment, CMR, PMR and stable metabolic disease was documented in 59%, 19% and 13% in the BV group vs. 71%, 17% and 3%, respectively, in the BVB group (p ns). Finally, 36 patients (22 from BV and 14 from BVB group) proceeded to ASCT, and 17 (9 from BV and 8 from BVB group) to allogeneic SCT. The overall and progression-free survival at 24 months were 80% and 51%. The survival curves did not differ between two study groups. In conclusion, our results suggest that BVB is a feasible regimen that provides higher response rate after 2 cycles compared to BV monotherapy. However, the overall response rate achieved after 4-6 cycles of treatment are comparable between BV monotherapy and combined BVB treatment. Infectious complications, including serious lung infections, were observed in both study groups, with two treatment-related deaths in the BVB group. Disclosures Dlugosz-Danecka: Roche: Consultancy; Servier: Consultancy. Jurczak:Nordic Nanovector: Research Funding; Epizyme: Research Funding; Beigene: Research Funding; Bayer: Research Funding; Celgene: Research Funding; Merck: Research Funding; Servier: Consultancy, Honoraria, Research Funding; European Medicines Agency: Consultancy; AstraZeneca: Consultancy; Gilead: Consultancy, Research Funding; Afimed: Research Funding; Morphosys: Research Funding; Janssen: Consultancy, Research Funding; Sandoz-Novartis: Consultancy; Roche: Research Funding; Pharmacyclics: Research Funding; Acerta: Consultancy, Research Funding; TG therapeutics: Research Funding. Zaucha:Roche: Honoraria; Takeda: Honoraria; Amgen: Honoraria; Celgene: Honoraria.

scholarly journals Real-Life Experience of Nivolumab in Heavily Pretreated Relapsed and Refractory Classical Hodgkin Lymphoma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3008-3008 ◽  
Author(s):  
Ohad Benjamini ◽  
David Lavie ◽  
Eldad J Dann ◽  
Chava Perry ◽  
Ory Rouvio ◽  
...  
Keyword(s):  
Adverse Events ◽  
Hodgkin Lymphoma ◽  
Clinical Studies ◽  
Life Experience ◽  
Real Life ◽  
Brentuximab Vedotin ◽  
Efficacy And Safety ◽  
Classical Hodgkin Lymphoma ◽  
Post Transplantation ◽  
Heavily Pretreated

Abstract Background: The fully human IgG4 anti-PD-1 monoclonal antibody, nivolumab, has shown to be highly efficacious in relapsed and refractory (RR) classical Hodgkin lymphoma (cHL). Initial results of a single-arm nivolumab monotherapy in heavily pretreated young adults with RR cHL, previously treated with autologous hematopoetic stem cell transplantation (autoSCT) and brentuximab vedotin are promising. However, demonstrating similar results in real-life experience in patients not on Pharma clinical studies are of major clinical importance. Aim: The aim of the current study was to evaluate the efficacy and safety of nivolumab in previously heavily pretreated patients with RR cHL not on Pharma clinical studies. Methods: The records of patients with RR cHL who were treated with nivolumab in seven medical centers were reviewed. The regimen consisted of nivolumab 3 mg/kg once every 2 weeks until disease progression or unacceptable toxicity. Results: Between May 2015 and April 2016, 30 patients with RR cHL received nivolumab monotherapy. The median age was 35 years (range: 21 to 88). Patients were extremely heavily pretreated with median of 6 prior therapies (range: 3 to 11); 73% of them received ≥ 5 lines of therapy. Specifically, 29/30 (97%) received ABVD, 7/30 (23%) escBEACOPP, 20/30 (67%) gemcitabine based regimens, 30/30 (100%) brentuximab vedotin, 8/30 (27%) bendamustine, 3/30 (10%) lenalidomide, 28/30 (93%) other combinations of chemotherapy and 22/30 (73%) radiotherapy. Twenty patients (67%) previously underwent autoHSCT and 4/30 (13%) allogeneic transplantation (alloSCT), two before and two after receiving nivolumab. Median number of nivolumab doses received was 8 (range 1 to 29). Twenty three patients (77%) are still on treatment. Seven patients (23%) discontinued therapy due to disease progression 3/30 (10%), adverse events 2/30 (7%) and referral to alloSCT 2/30 (7%). Overall response rate among 25 evaluable patients was 76%, complete response (CR) - 7/25 (28%), partial response - 12/25 (48%), stable disease - 3/25 (12%) and only 3/25 (12%) progressed, one of them with cHL type of Richter's transformation. Two patients underwent alloSCT in remission following nivolumab treatment. One patient was transplanted from a matched sibling donor and the second patient from a T replete haploidentical donor with post transplantation cyclophosphamide as anti-graft versus host disease prophylaxis. Both patients are in CR, ten and three months post transplantation, respectively. The median overall survival (OS) and progression free survival (PFS) for the cohort were not reached (Figure 1). At 24 weeks the PFS was 74%. Adverse events reported in 9/30 patients (30%) were usually mild. Severe nivolumab related adverse events in 3/30 (10%) included immune related pneumonitis, myelitis and uveitis. No treatment related death occurred. Conclusions: The check point inhibitor nivolumab is a novel therapy for RR cHL patients, previously with unmet need following relapse or refractory to autoHSCT and brentuximab vedotin. Our real life experience confirms and highlights the efficacy and safety of nivolumab in very heavily pretreated young and elderly patients with cHL eligible as well as ineligible for autologous HSCT. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Frontline Therapy with Brentuximab Vedotin Combined with ABVD or AVD in Patients with Newly Diagnosed Advanced Stage Hodgkin Lymphoma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 798-798 ◽  
Author(s):  
Stephen M. Ansell ◽  
Joseph M. Connors ◽  
Steven I. Park ◽  
Megan M. O'Meara ◽  
Anas Younes
Keyword(s):  
Hodgkin Lymphoma ◽  
Pulmonary Toxicity ◽  
Research Funding ◽  
Response Rate ◽  
Objective Response ◽  
Brentuximab Vedotin ◽  
Advanced Stage ◽  
Newly Diagnosed ◽  
Multi Agent ◽  
Frontline Therapy

Abstract Abstract 798 Hodgkin lymphoma (HL) is a lymphoid neoplasm associated with the presence of CD30-positive Hodgkin Reed-Sternberg cells in a background of inflammatory cells. The regimen containing doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) has become a common standard of care for the frontline treatment of HL. However, although ABVD is curative for the majority of patients with advanced stage HL, up to 30% of patients will require a salvage therapy. Brentuximab vedotin (ADCETRIS®) comprises an anti-CD30 monoclonal antibody conjugated by a protease-cleavable linker to a microtubule-disrupting agent, monomethyl auristatin E (MMAE). This phase 1, open-label, multicenter study was conducted to evaluate the safety of brentuximab vedotin when administered in combination with standard therapy (ABVD) or a modified standard (AVD) (ClinicalTrials.gov NCT01060904). Patients received doses of 0.6, 0.9, or 1.2 mg/kg brentuximab vedotin with standard doses of ABVD or 1.2 mg/kg brentuximab vedotin with AVD, depending upon cohort assignment. The combination regimens were administered on Days 1 and 15 of each 28-day cycle for up to 6 cycles of therapy. Each regimen evaluated a dose limiting toxicity (DLT) period, defined as any Cycle 1 toxicity requiring a delay of ≥ 7 days in standard ABVD or AVD therapy. Determination of antitumor activity was based on investigator assessment of objective response according to the Revised Response Criteria for Malignant Lymphoma (Cheson 2007). FDG-PET interpretation for Cycle 2 was performed by a central review per Deauville criteria with uptake above liver background considered positive. Data are presented for the 51 patients treated. Six patients received 0.6 mg/kg, 13 received 0.9 mg/kg, and 6 received 1.2 mg/kg with ABVD; 26 patients received 1.2 mg/kg with AVD. Overall, 37 patients were male (73%) and the median age of all patients was 33 years (range, 18–59). At baseline, 45% of all patients had Stage IV HL, 25% had an IPS score ≥4, and all patients with available ECOG status had a score of 0 or 1. No DLT was observed up to 1.2 mg/kg in either regimen. Common AEs (≥20 patients overall) noted in the ABVD and AVD cohorts, respectively, were nausea (76%, 77%), neutropenia (80%, 69%), peripheral sensory neuropathy (72%, 65%), vomiting (60%, 38%), fatigue (44%, 46%), and constipation (48%, 31%). Common ≥Grade 3 AEs (>10% of patients overall) observed in the ABVD and AVD cohorts, respectively, were neutropenia (80%, 65%), anemia (20%, 12%), febrile neutropenia (20%, 8%), and pulmonary toxicity (24%, 0%). In the ABVD cohorts, 11/25 (44%) patients had AEs of pulmonary toxicity, interstitial lung disease, or pneumonitis that led to discontinuation of bleomycin; 2 of these events led to death. Of these 11 patients, 7 completed treatment with AVD and brentuximab vedotin. In general, these events occurred between Cycles 3 and 6. No pulmonary toxicity was observed in the AVD cohort. The incidence of neuropathy was similar between the ABVD (72%) and AVD (73%) regimens; none of these events were ≥Grade 4 in severity. Overall, 7 patients discontinued brentuximab vedotin due to an AE (5 ABVD patients and 2 AVD patients). At Cycle 2, 48 patients were evaluated by FDG-PET by central review; of these, all 22 ABVD and 24/26 AVD patients were PET negative. Of the 51 patients treated, 4 withdrew consent or were lost to follow-up prior to end of treatment (EOT) assessments. The remaining 47 patients had a 96% objective response rate: 21/22 ABVD patients (95%) and 23/25 AVD patients (92%) achieved CR at the end of frontline therapy, 1 AVD patient had PR (with further workup ongoing), 1 ABVD patient died of AEs (hyponatremia and pulmonary toxicity) prior to EOT, and 1 AVD patient had PD. In patients with newly diagnosed HL, the maximum tolerated dose of brentuximab vedotin combined with ABVD or AVD was not reached; no DLT was observed up to 1.2 mg/kg every 2 weeks, the maximum planned dose. The safety profile observed confirmed that brentuximab vedotin can be safely combined with AVD; however, combination with a bleomycin-containing regimen is not recommended due to the incidence of pulmonary toxicity. The very high CR rate seen in this cohort of advanced-stage HL patients compares favorably with historical controls and warrants comparison with standard therapy. A phase 3 study comparing brentuximab vedotin combined with AVD versus ABVD alone is planned. Disclosures: Ansell: Seattle Genetics, Inc.: Research Funding; Celgene Corporation: Consultancy. Off Label Use: Brentuximab vedotin is indicated for treatment of patients with Hodgkin lymphoma after failure of autologous stem cell transplant or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not ASCT candidates and for the treatment of patients with systemic anaplastic large cell lymphoma after failure of at least one prior multi-agent chemotherapy regimen. These indications are based on response rate. There are no data available demonstrating improvement in patient reported outcomes or survival with brentuximab vedotin. Connors:Seattle Genetics, Inc.: Research Funding. Park:Seattle Genetics, Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Teva: Research Funding. O'Meara:Seattle Genetics, Inc.: Employment, Equity Ownership. Younes:Seattle Genetics, Inc.: Consultancy, Research Funding; Celgene: Honoraria; Novartis: Honoraria, Research Funding; Affimed: Research Funding; Gilead: Research Funding.

scholarly journals Pembrolizumab followed by AVD in untreated early unfavorable and advanced stage classical Hodgkin lymphoma

Blood ◽  
2020 ◽  
Author(s):  
Pamela Blair Allen ◽  
Hatice Savas ◽  
Andrew M Evens ◽  
Ranjana Advani ◽  
Brett Palmer ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Metabolic Response ◽  
Metabolic Tumor Volume ◽  
Advanced Stage ◽  
Newly Diagnosed ◽  
Classical Hodgkin Lymphoma ◽  
Bulky Disease ◽  
Positron Emission ◽  
Computed Tomography Scanning ◽  
Chemotherapy Patients

Pembrolizumab, a humanized IgG4 monoclonal antibody targeting programmed death-1 protein, has demonstrated efficacy in relapsed/refractory classical Hodgkin lymphoma (cHL). To assess the complete metabolic response (CMR) rate and safety of pembrolizumab monotherapy in newly diagnosed cHL, we conducted a multicenter, single-arm, phase II investigator-initiated trial of sequential pembrolizumab and doxorubicin, vinblastine, and dacarbazine (AVD) chemotherapy. Patients > 18 years of age with untreated early unfavorable or advanced stage disease were eligible for treatment. Thirty patients with either early unfavorable (n=12) or advanced (n=18) stage cHL were treated with 3 cycles of pembrolizumab monotherapy followed by AVD for 4-6 cycles depending on stage and bulk. Twelve had either large mediastinal masses and/or bulky disease (>10 cm). Following pembrolizumab monotherapy, 11 patients (37%) demonstrated CMR's, and an additional 7 of 28 (25%) patients with quantifiable positron emission tomography/computed tomography scanning (PET-CT) had >90% reductions in metabolic tumor volume. All patients achieved CMR following 2 cycles of AVD and maintained their responses at end of treatment. With a median follow-up of 22.5 months (range: 14.2-30.6) there have been no changes in therapy, progressions, or deaths. No patients received consolidation radiotherapy, including those with bulky disease. Therapy was well-tolerated. The most common immune-related adverse events were grade 1 rash (n=6), and grade 2 infusion reactions (n=4). One patient had a reversible grade 4 transaminitis and a second had a reversible Bell's palsy. Brief pembrolizumab monotherapy followed by AVD proved both highly effective and safe in newly diagnosed cHL patients including those with bulky disease. This trial was registered at www.clinicaltrials.gov as #NCT03226249.

scholarly journals Five-year follow-up of brentuximab vedotin combined with ABVD or AVD for advanced-stage classical Hodgkin lymphoma

Blood ◽  
2017 ◽  
Vol 130 (11) ◽  
pp. 1375-1377 ◽  
Author(s):  
Joseph M. Connors ◽  
Stephen M. Ansell ◽  
Michelle Fanale ◽  
Steven I. Park ◽  
Anas Younes
Keyword(s):  
Hodgkin Lymphoma ◽  
Brentuximab Vedotin ◽  
Advanced Stage ◽  
Classical Hodgkin Lymphoma

scholarly journals Update on the role of brentuximab vedotin in classical Hodgkin lymphoma

2018 ◽  
Vol 9 (9) ◽  
pp. 261-272 ◽  
Author(s):  
Sarah Tomassetti ◽  
Alex F. Herrera
Keyword(s):  
Hodgkin Lymphoma ◽  
Initial Treatment ◽  
Brentuximab Vedotin ◽  
Cell Transplant ◽  
Advanced Stage ◽  
Classical Hodgkin Lymphoma ◽  
Hematopoietic Stem ◽  
The Us ◽  
Us Fda

Brentuximab vedotin (BV) is an effective and well-tolerated treatment for patients with classical Hodgkin lymphoma (HL). It was initially approved by the US FDA for the treatment of HL after failure of autologous hematopoietic stem cell transplant (autoHSCT) or after failure of at least two prior lines of multiagent chemotherapy in patients who are not transplant candidates, and then subsequently, as consolidation therapy after autoHSCT in patients who are at high risk for relapse. However, the role of BV in the treatment of HL is evolving. BV has shown promising efficacy as a salvage treatment in the second-line setting prior to autoHSCT. Most recently, the ECHELON-1 trial demonstrated that BV combined with AVD for the treatment of newly diagnosed advanced stage HL improved modified progression-free survival (mPFS) compared with standard ABVD. Based on these results, the US FDA has approved BV as part of the initial treatment of advanced stage HL. With the approval of BV as front-line therapy, depending on how widely the use of BV plus AVD is adopted, the role of BV in the treatment of patients with relapsed or refractory (rel/ref) HL may need to be redefined. BV retreatment can be effective, and studies of rational BV-based combination regimens may help to improve response rates and overcome BV resistance. Furthermore, BV has been demonstrated to be effective in the initial treatment of elderly or unfit patients, and ongoing studies are evaluating the addition of BV to initial chemotherapy in patients with early stage HL.

scholarly journals Combination Brentuximab Vedotin and Bendamustine for Pediatric Patients with Relapsed/Refractory Hodgkin Lymphoma

2021 ◽  
Author(s):  
Christopher Jon Forlenza ◽  
Nitya Gulati ◽  
Audrey Mauguen ◽  
Michael Absalon ◽  
Sharon Castellino ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Pediatric Patients ◽  
Metabolic Response ◽  
Objective Response ◽  
Brentuximab Vedotin ◽  
Complete Metabolic Response ◽  
Highly Active ◽  
Common Grade ◽  
Infusion Reactions ◽  
Grade 3

In patients with relapsed/refractory (R/R) Hodgkin lymphoma (HL), achieving a complete metabolic response (CMR) following salvage therapy is associated with superior outcomes, and optimal treatments need to be identified. The combination of brentuximab vedotin and bendamustine (BVB), while highly active in adult patients, has not been extensively evaluated in pediatric patients with R/R HL. We performed a multi-institution retrospective review of pediatric patients <21 years of age with R/R HL treated with BVB from January 2016 to 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 15 years (range 10-20) were treated with BVB and received a median of three cycles of therapy (range 2-7). 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. Nineteen patients (66%) achieved a CMR (CI: 46 to 82%). An objective response was observed in 23 patients (ORR 79%) (CI: 60 to 92%). The most common grade 3/4 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 following BVB. The 3-year post-BVB event-free and overall survival was 65% (95%CI: 46 to 85%) and 89% (95%CI: 74 to 100), respectively. For pediatric patients with R/R HL, BVB was well tolerated and compares favorably with currently accepted salvage regimens.

Sign in / Sign up

Export Citation Format

Share Document