Concurrent pembrolizumab with AVD for untreated classic Hodgkin lymphoma

Author(s): Ryan C. Lynch1,2;Chaitra S. Ujjani1,2;Christina Poh1;Edus H. Warren1,2;Stephen D. Smith1,2;Mazyar Shadman1,2;Brian Till1,2;Vikram M. Raghunathan1;Stefan Alig3;Ash A. Alizadeh3Avanti Gulhane4;Delphine L. Chen4;Yolanda Tseng2,5;Hilary Coye1;Megan Shelby1;Susan Ottemiller1;Sarith Keo1;Kaitlin Verni1;Hongyan Du1;Jacquelin Vandermeer1;Ashley Gaston1;Heather Rasmussen1;Paul Martin1;Edmond Marzbani1;Jenna Voutsinas1;Ajay K. Gopal1,2
Source: Blood (2023) 141 (21): 2576–2586
Original Article
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Dr. Anjan Patel's Thoughts

Pembro + AVD for 1L treatment of cHL was associated with excellent responses, PFS and clearance of ctDNA. IO+chemo seems to be a growing trend in HL in various settings and theses response rates in non-Bleo regimens are very encouraging. The ongoing trial NCT05675410 comparing BV+AVD vs. Nivo+AVD should be a pivotal trial when complete.

KEY POINTS

Concurrent APVD was safe and effective in untreated HL without clinically significant treatment delays. CR rates by PET were lower than expected at all time points despite only one relapse, and no patient who cleared ctDNA has relapsed to date.

ABSTRACT

Concurrent administration of pembrolizumab with chemotherapy in untreated classic Hodgkin lymphoma (CHL) has not been studied previously. To investigate this combination, we conducted a single-arm study of concurrent pembrolizumab with AVD (doxorubicin, vinblastine, and dacarbazine; APVD) for untreated CHL. We enrolled 30 patients and met the primary safety end point with no observed significant treatment delays in the first 2 cycles. Twelve patients experienced grade 3 or 4 nonhematologic adverse events (AEs), most commonly febrile neutropenia and infection/sepsis. Grade 3 or 4 immune-related AEs, including alanine aminotransferase elevation and aspartate aminotransferase elevation were observed in 3 patients. One patient experienced an episode of grade 2 colitis and arthritis. Six patients missed at least 1 dose of pembrolizumab because of AEs, primarily grade 2 or higher transaminitis. Among 29 response-evaluable patients, the best overall response rate was 100% and the complete response rate was 90%. With a median follow-up of 2.1 years, the 2-year progression-free survival (PFS) and overall survival were 97% and 100%, respectively. To date, no patient who has withheld or discontinued pembrolizumab because of toxicity has progressed. Clearance of circulating tumor DNA (ctDNA) was associated with superior PFS when measured after cycle 2 and at the end of treatment (EOT). None of the 4 patients with persistent uptake by fluorodeoxyglucose positron emission tomography (PET) at EOT yet negative ctDNA have relapsed to date. Concurrent APVD shows promising safety and efficacy but may yield spurious PET findings in some patients. This trial was registered at www.clinicaltrials.gov as #NCT03331341.

Author Affiliations

1Division of Medical Oncology, University of Washington, Seattle, WA2Clinical Research Division, Fred Hutch Cancer Center, Seattle, WA3Division of Oncology, Stanford University, Stanford, CA4Department of Radiology, University of Washington, Seattle, WA5Department of Radiation Oncology, University of Washington, Seattle, WA

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