Zinzani PL, et al. ASH 2017:2833
Efficacy and safety of pembrolizumab in patients with R/R PMBCL: An updated interim analysis of the phase II KEYNOTE-170 study
Prognosis is poor for patients with relapsed or refractory (R/R) primary mediastinal B-cell lymphoma (PMBCL). Treatment options are especially limited for patients who have failed or who are ineligible for autologous stem cell transplantation (ASCT).1–3 In a phase Ib trial, pembrolizumab demonstrated promising antitumour activity with a manageable safety profile in patients with R/R PMBCL.4 Updated results of the phase II KEYNOTE-170 trial, which is investigating the efficacy and safety of pembrolizumab in this patient population, were presented at the 2017 ASH Annual Meeting.5
- KEYNOTE-170 is an ongoing, multicentre, phase II study investigating the efficacy and safety of pembrolizumab in patients with R/R PMBCL and in patients with R/R Richter syndrome.
- The present analysis included only the patients with PMBCL.
- The primary endpoint was overall response rate (ORR) by blinded, independent central review per International Working Group 2007 criteria.
- Secondary endpoints included duration of response (DOR), safety, and tolerability.
- Response assessments (by positron emission tomography/computed tomography scan) occurred at Week 12 and every 12 weeks thereafter.
- The efficacy population was comprised of the first 29 treated patients, all of whom had reached the Week 24 assessment or discontinued earlier by the time of database lock.
- All patients who received at least one dose of pembrolizumab were included in the safety population.
- A sample size of 50 patients was planned to allow 88% power to detect an ORR of 35% or higher with pembrolizumab compared with a 15% fixed control rate, using the exact binomial test.
Baseline characteristics and disposition
- A total of 53 patients were enrolled in the study.
- Median age was 33 years (range: 20–61).
- The majority of patients were female (57%), transplant ineligible (74%), had an Eastern Cooperative Oncology Group performance status of 1 (57%), and were positive for programmed death-ligand 1 (PD-L1) (64%).
- Patients received a median of three prior lines of therapy (range: 2–8) and had received rituximab as a prior treatment.
- Of all treated patients (n = 53), 19 (36%) are still undergoing treatment and 34 (64%) have discontinued treatment.
- Reasons for discontinuation were:
- Progressive disease (n = 14);
- Clinical progression (n = 12);
- Adverse event (n = 4);
- Physician decision (n = 3); and
- Complete response (n = 1).
- In the efficacy population (n = 29), 22 patients (76%) were positive for PD-L1, one patient (3%) was PD-L1 negative, and six patients (21%) had missing data.
- At the database cutoff of August 15, 2017, median duration of follow-up was 10.5 months (range: 0.1–17.7) in the efficacy population (n = 29).
- ORR was 41%, including 24% with complete responses and 17% with partial responses. (Table 1)
- Median time to response was 2.8 months (range: 2.4–5.5).
- Best responses in key patient subpopulations are summarized in Table 2.
- Median duration of response was not reached (range: 1.1+ to 13.6+ months).
- At the time of analysis, seven responses were ongoing and no responders had progressive disease.
- In three patients, partial response was converted to a complete response over time.
- Two patients underwent ASCT while in remission.
- A reduction in target lesions was observed in 16 of 22 evaluable patients (73%).
- Median duration of pembrolizumab treatment in all patients was 3.5 months (range: 0.03–17.2).
- Treatment-related adverse events (AEs) are summarized in Table 3.
- Immune-related AEs are summarized in Table 4.
- In patients with R/R PMBCL, including heavily pretreated patients, pembrolizumab had:
- A high response rate;
- An ability to induce durable responses, with some responses deepening over time; and
- A manageable safety profile consistent with prior experience of pembrolizumab in other tumour types.
References: 1. Martelli M, Di Rocco A, Russo E, et al. Primary mediastinal lymphoma: diagnosis and treatment options. Expert Rev Hematol 2015;8(2):173–86. 2. Zinzani PL, Pellegrini C, Chiappella A, et al. Brentuximab vedotin in relapsed primary mediastinal large B-cell lymphoma: results from a phase 2 clinical trial. Blood 2017;129(16):2328–30. 3. Jacobsen ED, Sharman JP, Oki Y, et al. Brentuximab vedotin demonstrates objective responses in a phase 2 study of relapsed/refractory DLBCL with variable CD30 expression. Blood 2015;125(9):1394–402. 4. Zinzani PL, Ribrag V, Moskowitz CH, et al. Safety and tolerability of pembrolizumab in patients with relapsed/refractory primary mediastinal large B-cell lymphoma. Blood 2017;130(3):267–70. 5. Zinzani PL, Thieblemont C, Melnichenko V, et al. Efficacy and safety of pembrolizumab in patients with relapsed or refractory primary mediastinal large B-cell lymphoma: an updated interim analysis of the phase 2 KEYNOTE-170 study. ASH Annual Meeting Abstracts 2017:2833.