NIVOLUMAB PLUS DOXORUBICIN, VINBLASTINE AND DACARBAZINE FOR NEWLY DIAGNOSED ADVANCED-STAGE CLASSICAL HODGKIN LYMPHOMA: 2-YEAR EXTENDED FOLLOW-UP FROM COHORT D OF THE PHASE 2 CHECKMATE 205 STUDY
Author(s): ,
Eva Domingo-Domènech
Affiliations:
Institut Català d'Oncologia (ICO),Barcelona,Spain
,
Radhakrishnan Ramchandren
Affiliations:
University of Tennessee,Knoxville,United States
,
Antonio Rueda
Affiliations:
Costa del Sol Hospital,Marbella,Spain
,
Marek Trněný
Affiliations:
Charles University in Prague and General University Hospital in Prague,Prague,Czech Republic
,
Tatyana Feldman
Affiliations:
Hackensack University Medical Center,Hackensack,United States
,
Hun Ju Lee
Affiliations:
University of Texas MD Anderson Cancer Center,Houston,United States
,
Mariano Provencio
Affiliations:
Hospital Universitario Puerta de Hierro,Madrid,Spain
,
Christian Sillaber
Affiliations:
Medical University of Vienna,Vienna,Austria
,
Jonathon B. Cohen
Affiliations:
Emory University,Atlanta,United States
,
Kerry J. Savage
Affiliations:
British Columbia Cancer Center for Lymphoid Cancer,Vancouver,Canada
,
Wolfgang Willenbacher
Affiliations:
Innsbruck University Hospital & OncoTyrol - Center for Personalized Cancer Medicine,Innsbruck,Austria
,
Anne Sumbul
Affiliations:
Bristol-Myers Squibb,Princeton,United States
,
Mariana Sacchi
Affiliations:
Bristol-Myers Squibb,Princeton,United States
,
Philippe Armand
Affiliations:
Dana-Farber Cancer Institute,Boston,United States
Stephen Ansell
Affiliations:
Mayo Clinic,Rochester,United States
EHA Library. Domingo-Domènech E. Jun 15, 2019; 267404; S821
Eva Domingo-Domènech
Eva Domingo-Domènech
Contributions
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Abstract

Abstract: S821

Type: Oral Presentation

Presentation during EHA24: On Saturday, June 15, 2019 from 12:15 - 12:30

Location: Hall 5

Background
Up to 30% of newly diagnosed patients (pts) with advanced-stage classical Hodgkin lymphoma (cHL) are not cured by multi-agent chemotherapy. High expression of the programmed death-1 (PD-1) ligands in these pts, associated with frequent genetic alterations at chromosome 9p24.1 in Hodgkin Reed-Sternberg cells, supports the investigation of front-line PD-1 blockade in cHL (Roemer MG et al. J Clin Oncol 2016). Promising activity and acceptable safety was previously reported in newly diagnosed pts with advanced-stage cHL treated with nivolumab, an anti–PD-1 immune checkpoint inhibitor monoclonal antibody, followed by nivolumab plus doxorubicin, vinblastine and dacarbazine (N-AVD) at a 9-month follow-up of Cohort D of the CheckMate 205 study (NCT02181738; Ramchandren R et al. EHA 2018).

Aims
To further characterize the efficacy, including post hoc Deauville assessment, and safety of nivolumab followed by N-AVD in pts with newly diagnosed advanced-stage cHL with 2-year extended follow-up of CheckMate 205 Cohort D.

Methods
Pts ≥ 18 years of age with newly diagnosed advanced-stage cHL (stage IIB with unfavorable risk factors, III, or IV) received 4 doses of nivolumab monotherapy (240 mg IV every 2 weeks) followed by N-AVD combination therapy for 6 cycles (12 doses). Primary endpoint was safety; secondary endpoints included complete remission (CR) rate per independent review committee (IRC) at end of study therapy (EOT) using 2007 International Working Group criteria. Complete metabolic response (CMR) was defined as a Deauville score of ≤ 3 (PET negative). Overall survival (OS) and modified progression-free survival (PFS) were exploratory endpoints; PFS was assessed in a post hoc analysis.

Results
Fifty-one pts were treated (median age 37 years); minimum follow-up was 24.4 months at data cutoff. Other baseline characteristics have been previously described (Ramchandren R et al. EHA 2018). Monotherapy was completed by 49/51 (96%) pts, combination therapy by 45/50 (90%); 48 pts entered follow-up. After 2 combination cycles, CR rate was 51% per IRC (71% CMR) and 71% per investigator; at EOT, CR rate was 69% (75% CMR) per IRC and 80% per investigator. At 21 months, modified PFS rate per investigator was 80% (95% CI, 66–89) and PFS rate per investigator was 83% (95% CI, 69–91; Figure). Overall, 30 (59%) pts experienced grade 3–4 TRAEs, most commonly neutropenia in 21 (41%). The most common grade 3–4 immune-mediated AE was hepatitis (2 pts, 4%). No grade 5 TRAEs occurred ≤ 30 days from last dose; 2 deaths were reported during the extended follow-up: 1 pt (age 68 years) died 38 days after last dose due to study drug toxicity; another (age 85 years) died 451 days after last dose due to disease progression.

Conclusion
With extended follow-up, nivolumab followed by N-AVD demonstrated a 21-month PFS rate of 83% per investigator, a high metabolic response rate with 75% CMR at EOT per IRC, with no new safety signals. Incorporation of Deauville assessment improved the concordance of CR between IRC- and investigator-assessed responses. Nivolumab followed by N-AVD provides a promising alternative treatment option in newly diagnosed advanced-stage cHL.

Session topic: 17. Hodgkin lymphoma - Clinical

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