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

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

Combination of COO and CNS-IPI improves CNS relapse prognosis in DLBCL

Jan 31, 2019

Bookmark this article

On 7 January 2019, Magdalena Klanova, from Charles University, First Faculty of Medicine, Prague, CZ, and colleagues, published in Blood a secondary analysis from the phase III trial GOYA (NCT01287741) were diffuse large B-cell lymphoma (DLBCL) were treated with either obinutuzumab or rituximab, plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP; G-CHOP versus R-CHOP).

The aim of this analysis was to investigate the impact of cell-of-origin (COO), central nervous system (CNS)-International Prognostic Index (IPI), and BCL2/MYC double-expression on CNS relapse in these patients. The primary endpoint of this retrospective analysis was time to CNS relapse.

Study design

  • N = 1418 previously untreated DLBCL patients, aged ≥ 18 with IPI ≥ 2 or IPI = 1 due to age alone or IPI = 0 with bulky disease (one lesion ≥ 7.5cm), Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2, and ≥ 1 bi-dimensionally measurable lesion
  • In the GOYA phase III trial, these patients were 1:1 randomized according to planned number of CHOP cycles, IPI, and geographic region to either:
    • G-CHOP (n = 706) or;
    • R-CHOP (n = 712)
  • Dosing:
    • G-CHOP: 1000 mg of G on Day 1,8, and 15 of cycle 1 and on Day 1 of cycles 2−8. CHOP for 6 or 8 cycles every 21 days
    • R-CHOP: 375 mg/m2 of R on Day 1 on cycles 1−8. CHOP for 6 or 8 cycles every 21 days
  • COO was assessed using gene expression profiling
  • BCL2 and MYC expression was assessed by immunohistochemistry
  • The impact of COO, CNS-IPI, and BCL2/MYC dual expression on CNS relapse was assessed with a multivariate Cox regression model on all N = 1418 randomized patients in the GOYA trial
  • Baseline characteristics:
    • CNS-IPI score:
      • Low risk: 19.7% of patients
      • Intermediate risk: 63.0% of patients
      • High risk: 17.3% of patients

Key results

  • COO analysis was possible in n = 933 patients, of whom:
    • Germinal center B-cell (GCB) subtype: 57.9% of patients
    • Activated B-cell (ABC) subtype: 26.0% of patients
    • Unclassified DLBCL: 16.1% of patients
  • Both COO and BCL2/MYC protein expression were available in n = 688 patients, of whom:
    • BCL2/MYC double-expressors: 42.9% of patients
  • More patients with the ABC subtype were BCL2/MYC double-expressors (70.5%) than those with the GCB subtype (30.7%) or unclassified DLBCL (36.8%)
  • After a median follow-up of 29 months (range, 24.5−4):
    • CNS relapse: n = 38 (2.7%) patients
      • Of those with CNS relapse, n = 37 patients had radiological signs of CNS relapse and/or infiltrated cerebrospinal fluid
    • Most CNS relapses were localized in the brain parenchyma (71.1%), the rest were leptomeningeal only (15.8%) or parenchymal and leptomeningeal (7.9%) or intraocular (2.6%) or data were unavailable (2.6%)
    • Median time to CNS relapse (range): 8.5 (0.9−43.5) months
    • The majority of CNS relapses occurred within two years from patient randomization (89.5%)
    • Two-year CNS relapse rates:
      • Total cohort: 2.8%
      • Low risk (CNS-IPI): 0.8% (95% CI, 0.0−1.9)
      • Intermediate risk (CNS-IPI): 1.9% (95% CI, 0.9−2.9)
      • High risk (CNS-IPI): 8.9% (95% CI, 4.7−12.9)
      • Patients receiving CNS prophylaxis: 2.8%
      • Patients not receiving CNS prophylaxis: 2.6%
      • In patients with COO available:
        • ABC subtype: 6.9%
        • GCB subtype: 1.3%
        • Unclassified DLBCL: 4.8%
        • Low risk (CNS-IPI): 1.4% (95% CI, 0.0−3.2)
        • Intermediate risk (CNS-IPI): 2.2% (95% CI, 0.9−3.5)
        • High risk (CNS-IPI): 9.6% (95% CI, 4.5−14.5)
      • Median survival after CNS relapse: 5.9 months
      • CNS relapses were similar in the G-CHOP and R-CHOP arms (20 versus 18), with no impact of the treatment on CNS relapse incidence rates
      • No significant association between BCL2/MYC double-expression and the risk of CNS relapse was identified by univariate analysis (P = 0.3196; two-year CNS relapse rate: double-expressors [4%] versus non-double-expressors [2.2%]; n = 688)
      • Multivariate analysis revealed the following factors associated with higher CNS relapse risk:
        • ABC subtype: HR = 5.2; (95% CI, 2.1−12.9); P = 0.0004
        • Unclassified COO subtype: HR = 4.2; (95% CI, 1.5−11.7); P = 0.006
        • High CNS-IPI: HR = 4.0; (95% CI, 1.3−12.3); P = 0.02
      • CNS-IPI and COO were combined to create a modified risk stratification model (CNS-IPI-C):
        • According to this model, three CNS-IPI-C subgroups were identified as having low (48.2%), intermediate (one risk factor; 43.7%) and high (two risk factors; 8.0%) CNS relapse risk
        • The two-year CNS relapse rates were:
          • Low CNS-IPI-C risk: 0.5% (95% CI, 0.0−1.3)
          • Intermediate CNS-IPI-C risk: 4.4% (95% CI, 2.2−6.6)
          • High CNS-IPI-C risk: 15.2% (95% CI, 5.4−24.0)
        • This modified model resulted in a 22-fold higher risk of CNS relapse in the high versus low CNS-IPI-C groups


  • There was no difference in CNS relapse in newly-diagnosed DLBCL patients treated with either G-CHOP or R-CHOP
  • High CNS-IPI score and ABC or unclassified COO subtypes were independent risk factors for CNS relapse in DLBCL
  • Combining CNS-IPI score and COO improved identification of DLBCL patients with different CNS relapse risks
  • No significant difference in the incidence of CNS relapse was observed between the intermediate and low risk CNS-IPI subgroups
  1. Klanova M. et al. Integration of COO into the clinical CNS International Prognostic Index could improve CNS relapse prediction in DLBCL. Blood. 2019 Jan 7. DOI: 10.1182/blood-2018-07-862862 [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

Which treatment do you select for patients with follicular lymphoma after multiple relapses?
0 votes - 6 days left ...


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