scholarly journals Phase II Trial of Pembrolizumab Plus Gemcitabine, Vinorelbine, and Liposomal Doxorubicin as Second-Line Therapy for Relapsed or Refractory Classical Hodgkin Lymphoma

2021 ◽  
pp. JCO.21.01056
Author(s):  
Alison J. Moskowitz ◽  
Gunjan Shah ◽  
Heiko Schöder ◽  
Nivetha Ganesan ◽  
Esther Drill ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Phase Ii ◽  
Liposomal Doxorubicin ◽  
Hematopoietic Cell Transplantation ◽  
Brentuximab Vedotin ◽  
High Dose ◽  
Second Line ◽  
Classical Hodgkin Lymphoma ◽  
Second Line Therapy ◽  
Line Therapy

PURPOSE We conducted a phase II study evaluating pembrolizumab plus gemcitabine, vinorelbine, and liposomal doxorubicin (pembro-GVD) as second-line therapy for relapsed or refractory (rel/ref) classical Hodgkin lymphoma (cHL) (ClinicalTrials.gov identifier: NCT03618550 ). METHODS Transplant eligible patients with rel/ref cHL following first-line therapy were treated with two to four cycles of pembrolizumab (200 mg intravenous [IV], day 1), gemcitabine (1,000 mg/m2 IV, days 1 and 8), vinorelbine (20 mg/m2 IV, days 1 and 8), and liposomal doxorubicin (15 mg/m2, days 1 and 8), given on 21-day cycles. The primary end point was complete response (CR) following up to four cycles of pembro-GVD. Patients who achieved CR by labeled fluorodeoxyglucose-positron emission tomography (Deauville ≤ 3) after two or four cycles proceeded to high-dose therapy and autologous hematopoietic cell transplantation (HDT/AHCT). HDT/AHCT was carried out according to institutional standards, and brentuximab vedotin maintenance was allowed following HDT/AHCT. RESULTS Of 39 patients enrolled, 41% had primary ref disease and 38% relapsed within 1 year of frontline treatment. 31 patients received two cycles of pembro-GVD, and eight received four cycles. Most adverse events were grade 1 or two, whereas few were grade 3 and included transaminitis (n = 4), neutropenia (n = 4), mucositis (n = 2), thyroiditis (n = 1), and rash (n = 1). Of 38 evaluable patients, overall and CR rates after pembro-GVD were 100% and 95%, respectively. Thirty-six (95%) patients proceeded to HDT/AHCT, two received pre-HDT/AHCT involved site radiation, and 13 (33%) received post-HDT/AHCT brentuximab vedotin maintenance. All 36 transplanted patients are in remission at a median post-transplant follow-up of 13.5 months (range: 2.66-27.06 months). CONCLUSION Second-line therapy with pembro-GVD is a highly effective and well-tolerated regimen that can efficiently bridge patients with rel/ref cHL to HDT/AHCT.

Relapse After Early-Stage, Favorable Hodgkin Lymphoma: Disease Characteristics and Outcomes With Conventional or High-Dose Chemotherapy

2021 ◽  
Vol 39 (2) ◽  
pp. 107-115
Author(s):  
Paul J. Bröckelmann ◽  
Horst Müller ◽  
Teresa Guhl ◽  
Karolin Behringer ◽  
Michael Fuchs ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Early Stage ◽  
High Dose Chemotherapy ◽  
Sensitivity Analyses ◽  
High Dose ◽  
Second Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Significant Difference ◽  
First Diagnosis

PURPOSE We evaluated disease and treatment characteristics of patients with relapse after risk-adapted first-line treatment of early-stage, favorable, classic Hodgkin lymphoma (ES-HL). We compared second-line therapy with high-dose chemotherapy and autologous stem cell transplantation (ASCT) or conventional chemotherapy (CTx). METHODS We analyzed patients with relapse after ES-HL treated within the German Hodgkin Study Group HD10+HD13 trials. We compared, by Cox proportional hazards regression, progression-free survival (PFS) after relapse (second PFS) treated with either ASCT or CTx and performed sensitivity analyses with overall survival (OS) from relapse and Kaplan-Meier statistics. RESULTS A total of 174 patients’ disease relapsed after treatment in the HD10 (n = 53) and HD13 (n = 121) trials. Relapse mostly occurred > 12 months after first diagnosis, predominantly with stage I-II disease. Of 172 patients with known second-line therapy, 85 received CTx (49%); 70, ASCT (41%); 11, radiotherapy only (6%); and 4, palliative single agent therapies (2%). CTx was predominantly bleomycin, etoposide, doxorubicin cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP [68%]), followed by the combination regimen of doxorubicin, bleomycin, vinblastine, and dacarbazine (19%), or other regimens (13%). Patients aged > 60 years at relapse had shorter second PFS (hazard ratio [HR], 3.0; P = .0029) and were mostly treated with CTx (n = 33 of 49; 67%) and rarely with ASCT (n = 8; 16%). After adjustment for age and a disadvantage of ASCT after the more historic HD10 trial, we did not observe a significant difference in the efficacy of CTx versus ASCT for second PFS (HR, 0.7; 95% CI, 0.3 to 1.6; P = .39). In patients in the HD13 trial who were aged ≤ 60 years, the 2-year, second PFS rate was 94.0% with CTx (95% CI, 85.7% to 100%) versus 83.3% with ASCT (95% CI, 71.8% to 94.8%). Additional sensitivity analyses including OS confirmed these observations. CONCLUSION After contemporary treatment of ES-HL, relapse mostly occurred > 12 months after first diagnosis. Polychemotherapy regimens such as BEACOPP are frequently administered and may constitute a reasonable treatment option for selected patients with relapse after ES-HL.

Phase II Trial of 5-Fluorouracil and High-Dose Folinic Acid as First- or Second-Line Therapy for Advanced Breast Cancer

1994 ◽  
Vol 17 (2) ◽  
pp. 175-180 ◽  
Author(s):  
Kim A. Margolin ◽  
Stephanie Green ◽  
Kent Osborne ◽  
James H. Doroshow ◽  
Steven A. Akman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Folinic Acid ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Advanced Breast ◽  
High Dose ◽  
Second Line ◽  
Second Line Therapy ◽  
Line Therapy

scholarly journals Emerging role of novel therapies in Hodgkin lymphoma: proceed with caution

Hematology ◽  
2017 ◽  
Vol 2017 (1) ◽  
pp. 317-323 ◽  
Author(s):  
Nancy L. Bartlett
Keyword(s):  
Hodgkin Lymphoma ◽  
Response Rates ◽  
Complete Response ◽  
Brentuximab Vedotin ◽  
New Drugs ◽  
Second Line ◽  
Second Line Therapy ◽  
First Line Therapy ◽  
Line Therapy ◽  
Stage Disease

AbstractBased on very high response rates in the relapsed and refractory setting, brentuximab vedotin and the programmed cell death protein 1 (PD-1) inhibitors, nivolumab and pembrolizumab, have quickly been incorporated into clinical trials for first- and second-line therapy of Hodgkin lymphoma. Preliminary data show that brentuximab vedotin alone is not adequate therapy for newly diagnosed Hodgkin lymphoma in older patients, but modestly decreases the risk of relapse when combined with adriamycin, vinblastine, and dacarbazine in patients with previously untreated advanced-stage disease. In second-line therapy, combining brentuximab vedotin with conventional chemotherapy or with PD-1 inhibitors as pretransplant salvage is associated with high overall and complete response rates, although further follow up is needed to assess whether posttransplant outcomes are improved. Although these new drugs are well tolerated when given as single agents, unexpected toxicities have been encountered with combination regimens, specifically severe pulmonary toxicity with the bleomycin and brentuximab vedotin combination and frequent infusion-related reactions. There is concern with the use of PD-1 inhibitors as first-line therapy due to the theoretical potential for more frequent or severe immune-mediated toxicities in patients who have not received prior chemotherapy. Aside from these concerns, these new agents have the potential to improve outcomes for patients even further, bringing us closer to eradicating recurrent Hodgkin lymphoma.

Phase II Study of Docetaxel and Gefitinib as Second-Line Therapy in Gemcitabine Pretreated Patients with Advanced Pancreatic Cancer

Oncology ◽  
2009 ◽  
Vol 76 (4) ◽  
pp. 270-274 ◽  
Author(s):  
Joanna M. Brell ◽  
Khalid Matin ◽  
Terry Evans ◽  
Robert L. Volkin ◽  
Gauri J. Kiefer ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Advanced Pancreatic Cancer ◽  
Second Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Pretreated Patients

Phase II study of biweekly plitidepsin as second-line therapy in patients with advanced malignant melanoma

2009 ◽  
Vol 19 (3) ◽  
pp. 185-192 ◽  
Author(s):  
Tim Eisen ◽  
José Thomas ◽  
Wilson H. Miller ◽  
Martin Gore ◽  
Pascal Wolter ◽  
...  
Keyword(s):  
Malignant Melanoma ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Second Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Advanced Malignant Melanoma
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