Autologous Hematopoietic Cell Transplant Outcomes after Pembrolizumab Plus GVD As Second-Line Therapy for Relapsed or Refractory Classical Hodgkin Lymphoma

The management of relapsed and refractory classic Hodgkin lymphoma (HL) has changed substantially since the approval of brentuximab vedotin (BV) and the checkpoint inhibitors nivolumab and pembrolizumab. For patients progressing after frontline treatment, second-line therapy followed by consolidation with autologous stem cell transplant (ASCT) remains the standard of care; however, although traditional combination chemotherapy regimens previously represented the only options for salvage, BV is now routinely incorporated into second-line therapy, and studies are evaluating checkpoint inhibitors in this setting as well. After ASCT, BV maintenance improves progression-free survival for patients at higher-risk, and studies are evaluating the role of post-ASCT maintenance with checkpoint inhibitors. Management of HL that progresses after ASCT remains a challenge. Although many patients achieve prolonged disease control with checkpoint inhibitors, the majority eventually progress and require additional therapy. Newer approaches, including CD30-directed chimeric antigen receptor–T-cell therapy, appear promising. Furthermore, allogeneic stem cell transplant remains an important consideration. Altogether, BV and checkpoint inhibitors have improved survival for patients with relapsed and refractory HL. However, the ideal place for these drugs in the treatment course of HL is still under investigation. Ongoing studies testing novel combinations and assessing for prognostic and predictive markers will ultimately define the optimal setting for these drugs in the treatment of relapsed and refractory HL.

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

Journal of Clinical Oncology ◽

10.1200/jco.21.01056 ◽

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.

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

Journal of Clinical Oncology ◽

10.1200/jco.20.00947 ◽

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.

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

Journal of Clinical Oncology ◽

10.1200/jco.21.01552 ◽

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.

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