TY - JOUR
T1 - Pembrolizumab followed by AVD in untreated early unfavorable and advanced-stage classical Hodgkin lymphoma
AU - Allen, Pamela B.
AU - Savas, Hatice
AU - Evens, Andrew M.
AU - Advani, Ranjana H.
AU - Palmer, Brett
AU - Pro, Barbara
AU - Karmali, Reem
AU - Mou, Eric
AU - Bearden, Jeffrey
AU - Dillehay, Gary
AU - Bayer, Robert A.
AU - Eisner, Robert M.
AU - Chmiel, Joan S.
AU - O'Shea, Kaitlyn
AU - Gordon, Leo I.
AU - Winter, Jane N.
N1 - Funding Information:
The authors thank the participating patients and their families and the nursing and clinical research staff who assisted with the study and particularly thank Merck & Co, Inc for its support. This work was supported by Merck & Co, Inc, which supplied funding for our investigator-initiated clinical trial and investigational product, and by National Institutes of Health, National Cancer Institute Cancer Center Support Grant P30 CA060553 to the Robert H. Lurie Comprehensive Cancer Center.
Publisher Copyright:
© 2021 American Society of Hematology
PY - 2021/3/11
Y1 - 2021/3/11
N2 - Pembrolizumab, a humanized IgG4 monoclonal antibody targeting programmed death-1 protein, has demonstrated efficacy in relapsed/refractory classical Hodgkin lymphoma (cHL). To assess the complete metabolic response (CMR) rate and safety of pembrolizumab monotherapy in newly diagnosed cHL, we conducted a multicenter, single-arm, phase 2 investigator-initiated trial of sequential pembrolizumab and doxorubicin, vinblastine, and dacarbazine (AVD) chemotherapy. Patients ≥18 years of age with untreated, early, unfavorable, or advanced-stage disease were eligible for treatment. Thirty patients (early unfavorable stage, n = 12; advanced stage, n = 18) were treated with 3 cycles of pembrolizumab monotherapy followed by AVD for 4 to 6 cycles, depending on stage and bulk. Twelve had either large mediastinal masses or bulky disease (>10 cm). After pembrolizumab monotherapy, 11 patients (37%) demonstrated CMRs, and an additional 7 of 28 (25%) patients with quantifiable positron emission tomography computed tomography scans had >90% reduction in metabolic tumor volume. All patients achieved CMR after 2 cycles of AVD and maintained their responses at the end of treatment. With a median follow-up of 22.5 months (range, 14.2-30.6) there were no changes in therapy, progressions, or deaths. No patients received consolidation radiotherapy, including those with bulky disease. Therapy was well tolerated. The most common immune-related adverse events were grade 1 rash (n = 6) and grade 2 infusion reactions (n = 4). One patient had reversible grade 4 transaminitis and a second had reversible Bell's palsy. Brief pembrolizumab monotherapy followed by AVD was both highly effective and safe in patients with newly diagnosed cHL, including those with bulky disease. This trial was registered at www.clinicaltrials.gov as #NCT03226249. Key Points: • Sequential pembrolizumab and AVD are highly active in untreated cHL, including cases of bulky disease. • Sequential pembrolizumab and AVD is safe in previously untreated cHL with limited immune-related toxicity.
AB - Pembrolizumab, a humanized IgG4 monoclonal antibody targeting programmed death-1 protein, has demonstrated efficacy in relapsed/refractory classical Hodgkin lymphoma (cHL). To assess the complete metabolic response (CMR) rate and safety of pembrolizumab monotherapy in newly diagnosed cHL, we conducted a multicenter, single-arm, phase 2 investigator-initiated trial of sequential pembrolizumab and doxorubicin, vinblastine, and dacarbazine (AVD) chemotherapy. Patients ≥18 years of age with untreated, early, unfavorable, or advanced-stage disease were eligible for treatment. Thirty patients (early unfavorable stage, n = 12; advanced stage, n = 18) were treated with 3 cycles of pembrolizumab monotherapy followed by AVD for 4 to 6 cycles, depending on stage and bulk. Twelve had either large mediastinal masses or bulky disease (>10 cm). After pembrolizumab monotherapy, 11 patients (37%) demonstrated CMRs, and an additional 7 of 28 (25%) patients with quantifiable positron emission tomography computed tomography scans had >90% reduction in metabolic tumor volume. All patients achieved CMR after 2 cycles of AVD and maintained their responses at the end of treatment. With a median follow-up of 22.5 months (range, 14.2-30.6) there were no changes in therapy, progressions, or deaths. No patients received consolidation radiotherapy, including those with bulky disease. Therapy was well tolerated. The most common immune-related adverse events were grade 1 rash (n = 6) and grade 2 infusion reactions (n = 4). One patient had reversible grade 4 transaminitis and a second had reversible Bell's palsy. Brief pembrolizumab monotherapy followed by AVD was both highly effective and safe in patients with newly diagnosed cHL, including those with bulky disease. This trial was registered at www.clinicaltrials.gov as #NCT03226249. Key Points: • Sequential pembrolizumab and AVD are highly active in untreated cHL, including cases of bulky disease. • Sequential pembrolizumab and AVD is safe in previously untreated cHL with limited immune-related toxicity.
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U2 - 10.1182/blood.2020007400
DO - 10.1182/blood.2020007400
M3 - Article
C2 - 32992341
AN - SCOPUS:85100416811
SN - 0006-4971
VL - 137
SP - 1318
EP - 1326
JO - Blood
JF - Blood
IS - 10
ER -