scholarly journals Brentuximab vedotin and ESHAP is highly effective as second-line therapy for Hodgkin lymphoma patients (long-term results of a trial by the Spanish GELTAMO Group)

2019 ◽  
Vol 30 (4) ◽  
pp. 612-620 ◽  
Author(s):  
R. Garcia-Sanz ◽  
A. Sureda ◽  
F. de la Cruz ◽  
M. Canales ◽  
A.P. Gonzalez ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Brentuximab Vedotin ◽  
Long Term Results ◽  
Second Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Highly Effective

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.

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.

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.

Optimizing Second-Line Therapy for Hodgkin Lymphoma: A Work in Progress

2021 ◽  
pp. JCO.21.01552
Author(s):  
Nancy L. Bartlett
Keyword(s):  
Clinical Practice ◽  
Hodgkin Lymphoma ◽  
Relevant Literature ◽  
Second Line ◽  
Clinical Context ◽  
Second Line Therapy ◽  
Case Presentation ◽  
Line Therapy ◽  
Management Approaches ◽  
Grand Rounds

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.

scholarly journals Obeticholic acid—a new therapy in PBC and NASH

2020 ◽  
Vol 133 (1) ◽  
pp. 95-104 ◽  
Author(s):  
Roger W Chapman ◽  
Kate D Lynch
Keyword(s):  
Clinical Trials ◽  
Side Effects ◽  
Ursodeoxycholic Acid ◽  
Farnesoid X Receptor ◽  
Primary Biliary Cholangitis ◽  
Second Line ◽  
Obeticholic Acid ◽  
Second Line Therapy ◽  
Line Therapy

Abstract Introduction Obeticholic acid (OCA) is a semi-synthetic hydrophobic bile acid (BA) analogue that is highly selective agonist of farnesoid X receptor (FXR), a key nuclear BA receptor, which induces expression of gut-derived hormones, in particular fibroblast growth factor 19. The resulting beneficial effects of OCA on glucose and lipid metabolism and particularly hepatic inflammation make it a candidate for the treatment of a variety of conditions including primary biliary cholangitis (PBC) and nonalcoholic steatohepatitis (NASH). Sources of data In PBC patients who have not initially responded to ursodeoxycholic acid, OCA has been shown in double-blind controlled clinical trials to significantly reduce serum alkaline phosphatase. To date, OCA is the only therapy licensed by the FDA, EMA and endorsed by NICE as second line therapy for PBC. No medications are currently approved in Europe or the USA for the treatment of NASH. In recent clinical trials, OCA has been shown encouraging results by improving liver blood tests and reducing liver fibrosis with no worsening of NASH. Areas of agreement OCA is the established second line therapy for PBC in those patients who fail to adequately respond to ursodeoxycholic acid. Areas of controversy The main side effects of OCA treatment in both PBC and NASH is that of dose-dependent pruritis which can lead to treatment discontinuation in ~1–10% of patients. In addition, OCA-treated patients may also exhibit (reversible) alterations in serum lipid levels; most notably a small decrease in high density lipoprotein cholesterol. It is not yet known whether these changes carry a long-term cardiovascular risk in NASH. In addition, the relatively high cost of OCA may limit its use in cash-limited health systems. Growing Points Additional clinical trials are in progress to ascertain the long-term effects of OCA on survival in PBC and NASH. Areas timely for developing research New FXR agonists with a lower rate of side effects are being developed and trialed. Combination therapy with other agents may offer increased efficacy.

How I treat autoimmune hemolytic anemias in adults

Blood ◽  
2010 ◽  
Vol 116 (11) ◽  
pp. 1831-1838 ◽  
Author(s):  
Klaus Lechner ◽  
Ulrich Jäger
Keyword(s):  
Underlying Disease ◽  
Second Line ◽  
Limited Information ◽  
Second Line Therapy ◽  
Term Efficacy ◽  
Line Therapy ◽  
Steroid Dependent ◽  
Common Causes ◽  
Anti Cd20

Abstract Autoimmune hemolytic anemia is a heterogeneous disease with respect to the type of the antibody involved and the absence or presence of an underlying condition. Treatment decisions should be based on careful diagnostic evaluation. Primary warm antibody autoimmune hemolytic anemias respond well to steroids, but most patients remain steroid-dependent, and many require second-line treatment. Currently, splenectomy can be regarded as the most effective and best-evaluated second-line therapy, but there are still only limited data on long-term efficacy and adverse effects. The monoclonal anti-CD20 antibody rituximab is another second-line therapy with documented short-term efficacy, but there is limited information on long-term efficacy and side effects. The efficacy of immunosuppressants is poorly evaluated. Primary cold antibody autoimmune hemolytic anemias respond well to rituximab but are resistant to steroids and splenectomy. The most common causes of secondary autoimmune hemolytic anemias are malignancies, immune diseases, or drugs. They may be treated in a way similar to primary autoimmune hemolytic anemias, by immunosuppressants or by treatment of the underlying disease.

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