CheckMate 436: Nivolumab plus brentuximab vedotin for R/R PTCL and CTCL

Patients with relapsed/refractory (R/R) peripheral T-cell lymphoma (PTCL) or cutaneous T-cell lymphoma (CTCL) have poor outcomes.¹  Overexpression of PD-L1 and CD30 is often observed in patients with PTCL (15–41% and 46–100%, respectively) and CTCL (27–73% and 47–76%, respectively).¹ Nivolumab is a checkpoint inhibitor that targets PD-1/PD-L1 binding, and brentuximab vedotin (BV) is an anti-CD30 antibody-drug conjugate.¹ BV was approved by the U.S. Food and Drug Administration (FDA) for the treatment of patients with CTCL, based on results from the phase III ALCANZA trial (NCT01578499) which were previously reported by the Lymphoma Hub.¹

Zinzani et al.¹ recently published an analysis of nivolumab plus BV in PTCL and CTCL cohorts of the phase I/II CheckMate 436 trial (NCT02581631) in Blood Advances, which we summarize below.

Study design¹

• The phase I/II CheckMate 436 trial included adult patients with R/R PTCL or CTCL who had received ≥1 prior line of therapy.
• Patients received 240 mg nivolumab on Day 8 of Cycle 1, and Day 1 of each subsequent 3-week cycle, plus 1.8 mg/kg BV intravenously on Day 1 of each cycle until progressive disease or unacceptable toxicity.
• The primary endpoint was overall response rate.

Key findings¹

Patient characteristics

• In total, 62 patients with PTCL (n = 33) and CTCL (n = 29) received treatment
• The median age was 60 years and 61 years in the PTCL and CTCL cohorts, respectively

Efficacy

• In the PTCL and CTCL cohorts:
  • the median follow-up was 9.6 months and 24.4 months, respectively;
  • the median duration of response was 4.6 months and 27.0 months, respectively;
  • median progression-free survival was 4.3 and 15.6 months, respectively; and
  • median overall survival was 11.1 and 37.2 months, respectively.

Response rates for the PTCL and CTCL cohorts are shown in Figure 1.

CTCL, cutaneous T-cell lymphoma; PTCL, peripheral T-cell lymphoma.
*Data from Zinzani, et al.¹

Safety

• In the PTCL cohort:
  • Overall, 84.8% of patients experienced any grade treatment-related adverse events (TRAEs), most commonly fatigue (24.2%)
  • Grade 3/4 TRAEs occurred in 45.5% of patients, most commonly neutropenia (15.2%)
  • In total, one patient experienced Grade 5 treatment-related pneumonitis
• In the CTCL cohort:
  • Overall, 89.7% of patients experienced any grade TRAEs, most commonly peripheral neuropathy (27.6%).
  • Grade 3/4 TRAEs were reported in 44.8% of patients, of which 13.8% were skin-related.
  • Overall, 40 deaths were reported in the PTCL (n = 26) and CTCL (n = 14) cohorts, most commonly due to progressive disease (n = 21 and n = 11, respectively). One death was due to treatment-related Grade 5 pneumonitis in the PTCL cohort.

Key learnings
The ORR observed with nivolumab plus BV in this analysis was similar to previous studies investigating PD-1 inhibitor monotherapies in patients with PTCL and CTCL; therefore, these results do not support the use of nivolumab plus BV in this patient population. Further studies are warranted to identify which disease subtypes may benefit from this combination therapy.