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CheckMate 205: Nivolumab in Newly Diagnosed, Advanced Classical Hodgkin Lymphoma

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Key Points

  • The objective response rate was 84%, with complete remission in 67% of patients.
  • Treatment-related grade 3 or 4 adverse events occurred in 59% of patients, with the most commonly reported being neutropenia and febrile neutropenia.

Findings in a cohort of the phase II CheckMate 205 study, reported in the Journal of Clinical Oncology by Ramchandren et al, indicate that nivolumab monotherapy followed by nivolumab plus doxorubicin, vinblastine, and dacarbazine (N-AVD) is highly active in newly diagnosed, advanced-stage classical Hodgkin lymphoma.

The cohort included 51 patients treated with nivolumab at 240 mg every 2 weeks for four doses, followed by six combination cycles (12 doses once every 2 weeks) of N-AVD (nivolumab at 240 mg, doxorubicin at 25 mg/m2, vinblastine at 6 mg/m2, and dacarbazine at 375 mg/m2). At diagnosis, 49% of patients had an International Prognostic Score of 3 or greater.

Patient Outcomes

The objective response rate on independent radiology review committee assessment was 84%, with 67% of patients achieving complete remission. Five nonevaluable patients (10%) were counted as nonresponders.

With a minimum follow-up of 9.4 months, the 9-month modified progression-free survival (defined as time to disease progression/relapse, death, or next therapy) was 92%. Among 38 patients with available Hodgkin Reed-Sternberg programmed cell death ligand 1 expression data, those with expression in the highest two quartiles had more favorable responses to N-AVD (P = .041).

Adverse Events

Grade 3 or 4 treatment-related adverse events occurred in 59% of patients, with the most common being neutropenia (49%) and febrile neutropenia (10%). Thirty patients (59%) received growth factors, all after starting combination therapy and usually as secondary prophylaxis.

Treatment-related serious adverse events occurred in 14% of patients, most commonly febrile neutropenia (4%) and infection (4%). Endocrine immune-mediated adverse events, consisting of hyperthyroidism/thyroiditis in nine patients (18%) and hypothyroidism in four (8%), were all grade 1 to 2 and did not require high-dose corticosteroids. Adverse events led to treatment discontinuation in four patients (8%), with causes consisting of febrile neutropenia, hyperthyroidism, abnormal hepatic function, and interstitial lung disease.

The investigators concluded: “Nivolumab followed by N-AVD was associated with promising efficacy and safety profiles for newly diagnosed, advanced-stage [classical Hodgkin lymphoma].”

Radhakrishnan Ramchandren, MD, of the University of Tennessee, Knoxville, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by Bristol-Myers Squibb, the Center for Immuno-Oncology of the Dana-Farber Cancer Institute, a National Cancer Institute grant, and Miller Family Fund. For full disclosures of the study authors, visit jco.ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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