A Phase I Study of Blinatumomab/Lenalidomide in Relapsed/Refractory B cell Lymphoma; Toxicity, Efficacy and Correlative Analysis Open Access

• Blinatumomab and lenalidomide was well tolerated and produced encouraging responses and durable remissions in heavily pre-treated B-Cell NHL

• Correlative analysis provides a better understanding of the mechanism of action and identification of predictive biomarkers

Despite a recent increase in therapeutic options, patients with relapsed B-cell non-Hodgkin lymphoma (R/R B-NHL) eventually require novel therapies. We conducted a phase I trial of blinatumomab and lenalidomide in R/R B-NHL. Three dose levels representing 2 schedules were explored. The primary endpoints were adverse events (AEs) and determining the MTD/RP2D. Thirty-five patients were enrolled, and thirty-four 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 two dose levels. Dose level 3, 20 mg of lenalidomide daily on days 1-21 and days 29-49 of a 56 day induction cycle plus blinatumomab 9 µg/day continuous intravenous infusion (CIVI) on days 1-7, 28 µg/day CIVI on days 8-14, and 112 µg/day CIVI on days 15-56 was determined to be the MTD/RP2D. The most common grade 2 or higher AE was neurotoxicity in 11/34 (32%), with 4/16 (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 ORR was 80% (95% CI, 56-94) with a CRR of 70%, and 8/34 (24%) had durable remissions lasting more than 2 years. GranB+ CD56bright CD16dim CD11b+ NK cells and memory T reg 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 pre-treated R/R B-NHL. NCI Protocol # 9924