A phase 1 study of blinatumomab/lenalidomide in relapsed/refractory B-cell lymphoma: toxicity, efficacy, and correlative analysis.

Despite a recent increase in therapeutic options, patients with relapsed/refractory B-cell non-Hodgkin lymphoma (R/R B-NHL) eventually require novel therapies. We conducted a phase 1 trial of blinatumomab and lenalidomide in R/R B-NHL. Three dose levels representing 2 schedules were explored. The primary end points were adverse events (AEs) and determining the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D). Thirty-five patients were enrolled, and 34 patients initiated treatment with a median number of prior regimens of 3 (range, 2-8). There were no dose-limiting toxicities (DLTs) in the first 2 dose levels. Dose level 3, 20 mg of lenalidomide daily on days 1 to 21 and days 29 to 49 of a 56-day induction cycle plus blinatumomab 9 μg/d continuous IV infusion (CIVI) on days 1 to 7, 28 μg/d CIVI on days 8 to 14, and 112 μg/d CIVI on days 15 to 56 was determined to be the MTD/RP2D. The most common grade ≥2 AE was neurotoxicity in 11 of 34 patients (32%), with 4 of 16 patients (25%) at the RP2D. At the RP2D, there was 1 DLT, a patient with grade 2 tremor and word-finding difficulty. For all patients completing induction, the overall response rate was 80% (95% confidence interval, 56-94) with a complete response rate of 70%, and 8 of 34 patients (24%) had durable remissions lasting >2 years. GranB+ CD56bright CD16dim CD11b+ natural killer cells and memory regulatory T cells in the peripheral blood at baseline were predictive of response. Concomitant administration of lenalidomide appeared to reduce blinatumomab-mediated T-cell exhaustion. In conclusion, encouraging activity was seen with blinatumomab and lenalidomide in heavily pretreated R/R B-NHL (NCI Protocol no. 9924).