Pembrolizumab for R/R T-cell lymphoma: Results from a phase II trial

On 2 April 2019, Stefan Barta from the Fox Chase Cancer Center & the University of Pennsylvania, Pennsylvania, PA, USA, and colleagues, published in Clinical Lymphoma, Myeloma & Leukemia results from the first prospective phase II trial (NCT02535247) that investigated the efficacy of pembrolizumab for the treatment of relapsed of refractory (R/R) mature T-cell lymphoma.

Pembrolizumab is a programmed cell death-1 (PD-1) inhibitor. Since PD-1 along with its ligand PD-L1 are commonly expressed in T-cell lymphomas and considering the current unmet need for patients with R/R T-cell lymphomas, the investigators sought to examine whether pembrolizumab is safe and can provide durable responses in this setting. The primary endpoint of this multicenter, prospective, single-arm, phase II trial was progression-free survival (PFS). Secondary outcomes included overall survival (OS), overall response rate (ORR), duration of response (DoR), and safety.

Study design & baseline characteristics

• N = 18 patients with R/R mature T-cell lymphoma who had received ≥ 1 prior systemic therapy, with an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1, aged ≥ 18 years
• Most common patient histologies (N = 17; one patient had ineligible histology):
  • Peripheral T-cell lymphoma not otherwise specified (PTCL-NOS): n = 7 patients
  • Follicular T-cell lymphoma (FTL): n = 4 patients
  • Transformed mycosis fungoides: n = 3 patients
  • Other: n = 3 patients
• Dosing:
  • Pembrolizumab: 200 mg intravenously, every 3 weeks for up to two years until disease progression (PD) or unacceptable toxicity
• Median patient age (range): 71 (18−88) years
• Male patients: 47% (n = 8)
• Median number of prior lines (range): 2 (1−9)
  • Patients who had received > 2 prior lines: 35% (n = 6)
• Patients refractory to last treatment: 65% (n = 11)
• Two-stage study design with early stopping for futility if median PFS was ≤ 3 months (null hypothesis) versus ≥ 6 months

Key findings

• Fifteen out of 17 patients provided response data, since one patient developed pneumonitis after one treatment cycle and the other one died of an unrelated toxicity
• The trial was discontinued early for futility since six out of 11 patients evaluable for PFS at three months were progression free

Patients (response data)	N = 15
ORR (n)	33% (n = 5)	95% CI, 9−57
Complete response (CR; n)	27% (n = 4)	95% CI, 4−49
Median time to best response (range)	114 (81−146) days
Median follow-up	5.9 months	95% CI, 0−18
Median PFS	3.2 months	95% CI, 1.2−3.7
Median OS	10.6 months	95% CI, 3.2−100

• Patients discontinuing study: 88%
  • Reasons for discontinuation:
    • PD: n = 11 patients
    • Death: n = 1 patient
    • Toxicities: n = 2 patients
  • Amongst the responders:
    • None experienced PD on treatment
    • One patient discontinued treatment due to vasculitis
    • One patient came off in CR to receive a hematopoietic stem cell transplant
    • Two patients remain in remission after > 15 months, still receiving treatment (median DoR, 2.9 months; 95% CI, 0−1)

Safety

• The most common adverse events (AEs) were:
  • Rash: 17% (n = 3)
  • Hypothyroidism: 11% (n = 2)
  • Watering eyes: 11% (n = 2)
  • Chills: 11% (n = 2)
  • Edema: 11% (n = 2)
  • Fatigue: 11% (n = 2)
  • Fever: 11% (n = 2)
  • Injection reactions: 11% (n = 2)
  • Dyspnea: 11% (n = 2)
  • Pneumonitis: 11% (n = 2)
• Number of patients who experienced Grade ≥ 3 AEs: 67% (n = 12)
  • Of those, 22% (n = 4) were considered treatment-related
• Most common treatment-related Grade ≥ 3 AEs:
  • Pneumonitis (11%; n = 2)
  • Rash (11%; n =2)
• No treatment-related deaths occurred. But one patient died while on treatment (septic shock)
• Immune-related AEs occurred in n = 12 patients

Conclusions

According to the authors, the ORR observed in this trial (33%), with single-agent pembrolizumab in patients with R/R T-cell lymphoma, is comparable to other available monotherapy agents. In general, the PD-1 inhibitor showed modest activity and the expected toxicity profile. The main limitation of this study was its small sample size. Larger prospective studies are needed to validate the results of this trial.