Efficacy and safety of rituximab and pembrolizumab in R/R WM: PembroWM trial

Results from a phase II, non-randomized, open-label, single-arm study (PembroWM; NCT03630042) evaluating efficacy and safety of pembrolizumab, a PD-1 inhibitor, and rituximab combination therapy in the treatment of relapsed/refractory (R/R) Waldenstrom's macroglobulinemia (WM) were published by Kothari et al.¹ in British Journal of Haematology.

A total of 17 patients were included; 88% of patients were pretreated with covalent Bruton’s tyrosine kinase inhibitors (cBTKi) and 71% were refractory/intolerant to cBTKi.

The primary endpoint was not met as overall response was only achieved in 7 patients (very good partial response, 1; partial response, 3; minor response, 3) at Week 24.

• The median duration of response was 11.6 months.
• At a median of 3.1 months, the best overall response rate was 52.9%.

Median progression-free survival (PFS) was 13.6 months; 1- and 2-year PFS rates were 58.2% and 19.4%, respectively.

Median overall survival (OS) was not reached; 1- and 2-year OS rates were 92.9% and 67%, respectively.

The 1- and 2-year time to next treatment rates were 72.7% and 43.1%, respectively.

Adverse events (AEs) were observed in 94% of patients.

• Most common Grade 1–2 AEs were anemia, fatigue, fever, raised creatinine, infusion-related reactions, cough, dizziness, hypotension, and neutropenia.
• Five deaths were reported, all unrelated to the treatment.
• One immune-related AE was observed, in line with the known AEs with PD-1 inhibitors.
  

There were no significant improvements in quality-of-life scores in the majority of patients, except for emotional (p = 0.02) and cognitive functioning (p = 0.03).

The results indicate that the combination of pembrolizumab and rituximab is feasible and tolerable in patients with R/R WM, including those who have been heavily pretreated and are refractory to cBTKi. Further research is needed to explore the modulation of PD-1 axis in the management of WM.