Work

A Pilot Trial of Adriamycin, Pembrolizumab, Vinblastine and Dacarbazine (apvd) for Patients With Untreated Classical Hodgkin Lymphoma

Year: 2019

Type: article

Abstract: 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. While it demonstrated a modest modified PFS benefit, it was associated with notable toxicities including higher rates of neuropathy and infection. PD1 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 PD1 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 for untreated CHL (NCT03331341). Methods: We designed a non-randomized, 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, 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. Keywords: chemotherapy; Hodgkin lymphoma (HL); Pembrolizumab. Disclosures: Lynch, R: Research Funding: Rhizen Pharmaceuticals, TG Therapeutics, Incyte Corporation, Takeda, Juno Therapeutics. Smith, S: Consultant Advisory Role: Merck Sharp and Dohme Corp, Astrazeneca; Research Funding: Acerta Pharma BV, Astrazeneca, Ayala (spouse), Bristol Myers Squibb (spouse), De Novo Biopharma, Genentech, Ignyta (spouse), Incyte Corporation, Merck Sharp and Dohme Corp. (Self, spouse), Pharmacyclics, Portola Pharmaceuticals, Seattle Genetics. Shadman, M: Consultant Advisory Role: Abbvie, Genentech, Sound Biologics; Verastem, ADC therapeutics and Atara Biotherapeutics; Research Funding: Mustang Biopharma, Celgene, Pharmacyclics, Gilead, Genentech, Abbvie, TG therapeutics, Beigene, Acerta Pharma, Merck. Kurtz, D: Consultant Advisory Role: Roche Molecular Diagnostics. Till, B: Research Funding: Mustang Biopharma; Other Remuneration: Patent/royalties: Mustang Biopharma. Shustov, A: Research Funding: Seattle Genetics. Maloney, D: Honoraria: Roche/Genentech, Janssen Scientific Affairs, Seattle Genetics; Research Funding: GlaxoSmithKline, Juno Therapeutics. Gopal, A: Consultant Advisory Role: Seattle Genetics, Pfizer, Janssen, Gilead, Spectrum, Amgen, Incyte, Aptevo, BRIM Bio, Sanofi; Research Funding: Teva, Bristol-Myers Squibb, Merck, Takeda, TG Therapeutics, Effector, Seattle Genetics, Pfizer, Janssen, Gilead, Spectrum, Amgen, Incyte.

Source: Hematological Oncology

DOI: 10.1002/hon.21_2632