Moskowitz CH, et al. ASH 2017:4085

Pembrolizumab antitumour activity in R/R cHL in KEYNOTE-087: Assessment of response by Revised Response Criteria for Malignant Lymphoma 2007 versus Lugano 2014 classification

Background

Pembrolizumab demonstrated effective antitumour activity and a tolerable safety profile in patients with relapsed or refractory (R/R) classic Hodgkin lymphoma (cHL) in the KEYNOTE-087 trial.1 In this trial, response was assessed using both the 2007 Revised Response Criteria for Malignant Lymphoma (Cheson criteria)2 and the 2014 Lugano criteria.3 The following report, presented at the 2017 ASH Annual Meeting, compared the response assessments of the two criteria in patients enrolled in KEYNOTE-087.4

Study design

  • KEYNOTE-087 was a phase II, open-label, multicentre study of pembrolizumab in patients with R/R cHL.
  • Pembrolizumab 200 mg was given every three weeks for up to two years or until documented confirmed disease progression, intolerable toxicity, or decision to withdraw (by patient or investigator).
  • Response was assessed by independent central review per Cheson 2007 and Lugano 2014 criteria every 12 weeks.
    • Computed tomography was performed every 12 weeks.
    • Positron emission tomography was performed at Weeks 12 and 24 to confirm complete response (CR) and as clinically indicated.
    • Bone marrow biopsy was performed at screening and to confirm CR in patients with bone marrow involvement.
  • Efficacy was evaluated in all patients who received at least one dose of pembrolizumab.
  • Data cutoff for analyses was March 21, 2017.

Key findings

  • The median follow-up was 15.9 months (range: 1.0–20.9).
  • Overall response rate was similar between Cheson and Lugano criteria (71.4% and 73.3%, respectively). (Figure 1)
  • Response per Cheson criteria was confirmed in 150 patients, 139 of whom also experienced a response per Lugano criteria. (Table 1)
    • Eleven patients who were responders per Cheson criteria were not responders per Lugano criteria.
    • Fifteen patients who were responders per Lugano criteria were not responders per Cheson criteria.
  • There was substantial agreement between Cheson and Lugano criteria when evaluating results by nonresponders versus responders (Kappa statistic: 0.67) and by best response (Kappa statistic 0.70). (Table 1)
  • Median time to response and duration of response (DOR) were similar for patients considered responders by either Cheson or Lugano criteria or both. (Figure 2)
  • Median progression-free survival (PFS) also appeared similar for these three categories of patients. (Table 2)

Figure 1. Best ORR per Cheson or Lugano criteria

Table 1. Agreement between responses per Cheson and Lugano criteria

Figure 2. Time to response and duration of response per Cheson and Lugano criteria

Table 2. PFS per Cheson and Lugano criteria

Key conclusions

  • This analysis demonstrated a strong agreement between responses as assessed per Cheson 2007 and Lugano 2014 criteria.
  • Clinical outcomes (DOR, PFS) appeared similar for patients who were classified as responders by both Cheson 2007 and Lugano 2014 criteria.
  • These findings suggest that both sets of criteria are appropriate in assessing response to anti–PD-1 therapy in patients with R/R cHL.

References: 1. Chen R, Zinzani PL, Fanale MA, et al. Phase II study of the efficacy and safety of pembrolizumab for relapsed/refractory classic Hodgkin lymphoma. J Clin Oncol 2017;35(19):2125–32. 2. Cheson BD, Pfistner B, Juweid ME, et al. Revised response criteria for malignant lymphoma. J Clin Oncol 2007;25(5):579–86. 3. Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol 2014;32(27):3059–68. 4. Moskowitz CH, Chen RW, Armand P, et al. Pembrolizumab antitumour activity in relapsed/refractory classic Hodgkin lymphoma in KEYNOTE-087: assessment of response by Revised Response Criteria for Malignant Lymphoma 2007 versus Lugano 2014 classification. ASH Annual Meeting Abstracts 2017:4085.