All content on this site is intended for healthcare professionals only. By acknowledging this message and accessing the information on this website you are confirming that you are a Healthcare Professional. If you are a patient or carer, please visit the Lymphoma Coalition.

The Lymphoma Hub uses cookies on this website. They help us give you the best online experience. By continuing to use our website without changing your cookie settings, you agree to our use of cookies in accordance with our updated Cookie Policy

Introducing

Now you can personalise
your Lymphoma Hub experience!

Bookmark content to read later

Select your specific areas of interest

View content recommended for you

Find out more
  TRANSLATE

The Lymphoma Hub website uses a third-party service provided by Google that dynamically translates web content. Translations are machine generated, so may not be an exact or complete translation, and the Lymphoma Hub cannot guarantee the accuracy of translated content. The Lymphoma Hub and its employees will not be liable for any direct, indirect, or consequential damages (even if foreseeable) resulting from use of the Google Translate feature. For further support with Google Translate, visit Google Translate Help.

Steering CommitteeAbout UsNewsletterContact
LOADING
You're logged in! Click here any time to manage your account or log out.
LOADING
You're logged in! Click here any time to manage your account or log out.

The Lymphoma & CLL Hub is an independent medical education platform, sponsored by Beigene and Roche, and supported through educational grants from Bristol Myers Squibb, Ipsen Biopharmaceuticals, Pfizer, and Pharmacyclics LLC, an AbbVie Company and Janssen Biotech, Inc., administered by Janssen Scientific Affairs, LLC. View funders.

2019-05-21T21:42:26.000Z

CheckMate 205: Nivolumab monotherapy followed by AVD combination for naïve, aggressive cHL

May 21, 2019
Share:

Bookmark this article

Nivolumab, a programmed death protein 1 (PD-1) antibody, is under accelerated approval by the US Food and Drug administration (FDA)1 for patients with relapsed and refractory (R/R) classical Hodgkin lymphoma (cHL), who have relapsed or progressed after autologous stem cell transplant (ASCT). For newly-diagnosed cHL, multiagent chemotherapy is the current standard of care.2,3 This has proved a good treatment strategy for early-stage, naive cHL but remains suboptimal for advanced-stage patients.2

The CheckMate 205 (NCT02181738)  phase II trial4 demonstrated that nivolumab monotherapy has an acceptable safety profile and leads to good and durable responses in patients with R/R cHL. In an extended cohort (Cohort D) of the CheckMate 205 study, single-agent nivolumab followed by a period of nivolumab in combination with doxorubicin, vinblastine, and dacarbazine (N-AVD), was evaluated for safety and efficacy in advanced-stage previously-untreated cHL. These results were published in the Journal of Clinical Oncology3 by Radhakrishnan Ramchandren from the University of Tennessee, Knoxville, TN, USA, and colleagues on 21 May 2019.

The primary endpoints of this analysis were safety and tolerability, measured as an increase in Grade 3–5 treatment-emergent adverse events (TEAEs) between first dose and one month after last dose. Secondary endpoints, included overall response rate (ORR) and complete response (CR) rate, as assessed by an independent radiology review committee (IRC).

Study design & baseline characteristics

  • Cohort D, CheckMate 205: N = 51 patients with untreated, advanced-stage cHL (Ann Arbor III–IV; or bulky Stage IIB), aged ≥18 years, with Eastern Cooperative Oncology Group (ECOG) performance status 0–1, and hemoglobulin-adjusted carbon monoxide lung diffusion capacity >60%
  • Patients were treated with nivolumab monotherapy and then with N-AVD combination therapy, as follows:
    • Nivolumab monotherapy phase: 4 doses of intravenous (IV) nivolumab (240mg over 30 minutes), once every 2 weeks
    • N-AVD combination phase: 12 doses of IV N-AVD, once every 2 weeks (six cycles):
      • Nivolumab: 240mg
      • Doxorubicin: 25mg/m2
      • Vinblastine: 6mg/m2
      • Dacarbazine: 375mg/m2
    • After the N-AVD combination phase, patients entered follow-up assessments at 39, 65, and 104 weeks after last N-AVD dose
  • Response assessment was performed by fludeoxyglucose-positron emission tomography (FDG-PET) and computed tomography (CT) or magnetic resonance imaging (MRI) at:
    • Baseline
    • End of monotherapy phase
    • After 2 combination therapy cycles (N-AVD)
    • End of treatment (EOT; 9 ±2 weeks from last dose)
Table 1. Key baseline characteristics

Baseline characteristic

Patients (N = 51)

Median age (range)

37 (18–87) years

Ann Arbor stage:

II

III

IV

 

20% (n= 10)

24% (n= 12)

57% (n= 29)

International Prognostic Index (IPI) score:

0–1

2–3

≥4

Unreported

 

24% (n= 12)

41% (n= 21)

25% (n= 13)

10% (n= 5)

Bulky disease

31% (n= 16)

Extranodal disease

49% (n= 25)

Key findings

Safety

  • Number of patients with TEAEs of any grade: 96% (n= 49)
  • Observed hematological toxicities of any grade:
    • Neutropenia: 55% (n= 28)
    • White blood count reduction: 14% (n= 7)
    • Febrile neutropenia: 10% (n= 5)
    • Anemia: 10% (n= 5)
    • Alanine aminotransferase (ALT) increase: 8% (n= 4)
    • Amylase increase: 6% (n= 3)
  • Number of patients with Grade 3–4 TEAEs: 59% (n= 30)
  • Most common Grade 3–4 hematological toxicities:
    • Neutropenia: 49% (n= 25)
    • White blood count reduction: 2% (n= 1)
    • Febrile neutropenia: 10% (n= 5)
    • Anemia: 4% (n= 2)
    • ALT increase: 4% (n= 2)
  • Patients with infusion-related reactions (all Grade 1–2):
    • During monotherapy: 29% (n= 15)
    • During N-AVD combination therapy: 6% (n= 3)
  • One Grade 5 TEAE was reported (combination cycle 5) leading from acute respiratory infection, febrile neutropenia, congestive heart failure, and acute respiratory failure

Efficacy

Table 2. Efficacy data per IRC at different study stages

 

At end of nivolumab  monotherapy

After two N-AVD combination cycles

At end of N-AVD combination treatment (EOT)

ORR (95% CI)
(N = 51)

69% (54–81)

90% (79–97)

84% (71–93)

CR rate (95% CI)
(N = 51)

18% (8–31)

51% (37–65)

67% (52–79)

Tumor lesion burden reduction >50%
(n/total evaluable patients)

71% (35/49)

98% (45/46)

100% (46/46)

Progressive disease (PD)

-

-

6%

  • At EOT, five patients (10%) were not evaluable for response due to:
    • Consent withdrawal (n= 1)
    • Lost to follow-up (n= 1)
    • Death (n= 1)
    • Monotherapy continuation at EOT (n= 1)
    • Lack of EOT assessment (n= 1)
  • ORR at EOT without the non-evaluable patients above (IRC; n= 46) was 93% and CR rate was 74%
  • With a minimum follow-up of 9.4 months:
    • Nine-month progression-free survival (PFS): 92% (95% CI, 80–97)
    • Median PFS: not reached
    • Nine-month overall survival (OS): 98% (95% CI, 86–100)

Conclusions

Nivolumab monotherapy, followed by a period of nivolumab in combination with AVD chemotherapy, showed a manageable safety profile and led to very good responses in previously-untreated, advanced-stage patients with cHL.

  1. FDA, 2016. Nivolumab (Opdivo) for Hodgkin Lymphoma | FDA. URL https://www.fda.gov/drugs/resources-information-approved-drugs/nivolumab-opdivo-hodgkin-lymphoma (accessed 04.06.19)
  2. Gordon L.I. et al. Randomized phase III trial of ABVD versus Stanford V with or without radiation therapy in locally extensive and advanced stage Hodgkin lymphoma: An intergroup study coordinated by the Eastern Cooperative Oncology Group (E2496). J Clin Oncol 2013 Feb 20;31(6):684-91. DOI: 10.1200/JCO.2012.43.4803 [Epub 2012 Nov 26]
  3. Ramchandren R. et al. Nivolumab for Newly Diagnosed Advanced-Stage Classic Hodgkin Lymphoma: Safety and Efficacy in the Phase II CheckMate 205 Study. J Clin Oncol. 2019 May 21:JCO1900315. DOI: 10.1200/JCO.19.00315 [Epub ahead of print]
  4. Armand P. et al. Nivolumab for Relapsed/Refractory Classic Hodgkin Lymphoma After Failure of Autologous Hematopoietic Cell Transplantation: Extended Follow-Up of the Multicohort Single-Arm Phase II CheckMate 205 Trial. J Clin Oncol. 2018 Mar 27. JCO2017760793. DOI: 10.1200/JCO.2017.76.0793 [Epub ahead of print]

Understanding your specialty helps us to deliver the most relevant and engaging content.

Please spare a moment to share yours.

Please select or type your specialty

  Thank you

Your opinion matters

HCPs, what is your preferred format for educational content on the Lymphoma Hub?
26 votes - 4 days left ...

Newsletter

Subscribe to get the best content related to lymphoma & CLL delivered to your inbox