https://orcid.org/0000-0001-6703-0894
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.
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Comments
Pembrolizumab + AVD as first line treatment on classical Hodgkin lymphoma: a query about the inclusion of patients with early favorable prognosis
We read with great interest the paper by Lynch et al published in Blood1, which showed that the addition of the check-point inhibitor Pembrolizumab to the polychemotherapy regimen AVD (doxorubicin, vinblastine, and dacarbazine) was safe and feasible for patients with newly diagnosed classical Hodgkin Lymphoma (cHL). This new approach might fill the gap in the overall survival (OS) curves between early favorable and advanced stages, based on the results shown in the paper. However, looking into the population treated with this new combination, we noticed that there were 6 patients (total n=29) who were considered as having early favorable prognosis per the National Comprehensive Cancer Network criteria. In our understanding, this population usually has a very good prognosis when treated with ABVD, with a 5-year probability of OS exceeding 90%2–4, with curable disease in most patients who achieve a negative end-of-treatment PET CT.
These previous published data led us to one question: considering that the present trial is an experimental treatment, and that patients with early favorable cHL have such good prognosis when treated with ABVD, wouldn’t it be more appropriate to have included only patients with advanced disease?