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).

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Publication Details

Journal
Blood Advances
Published
2025-11-10
DOI
https://doi.org/10.1182/bloodadvances.2025016845
Citations
1
Primary Topic
CAR-T cell therapy research
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article
Field-Weighted Citation Impact
1.05

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article

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

Mehrdad Abedi, Elad Sharon, Emanual Maverakis, Alexander A. Merleev et al.
1 citations
Blood Advances
CAR-T cell therapy research
1.05
article

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

Mehrdad Abedi, Elad Sharon, Emanual Maverakis, Alexander A. Merleev, Tamer Adel Othman, Joseph M. Tuscano, Aaron S. Rosenberg, Rasmus T. Hoeg, Christina Poh, Matthew Mei, Basem M. William, Raghuveer Ranganathan, Edward M. Newman, Lihua E. Budde, Paul Frankel, Guillaume Luxardi, Samantha Herbert, Dipenkumar Modi, Christopher Ruel, Francine M. Foss, Caitlin Costello, HOWARD Z. STREICHER, Jasmine M. Zain, H. Kent Holland, Alexey V. Danilov
article en
1 citations

Abstract

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).

Blood AdvancesVol. 10(4)
Northside Hospital (US), University of Southern California (US), City Of Hope National Medical Center (US), University of New Mexico Hospital (US), Memorial Sloan Kettering Cancer Center (US), University of California, San Francisco (US), Wayne State University (US), Yale Cancer Center (US), University of California San Diego (US), The Barbara Ann Karmanos Cancer Institute (US), City of Hope (US), Michigan United (US), Dana-Farber Cancer Institute (US), Short and Associates (United States) (US), National Cancer Institute (MY), National Cancer Institute (US), VA Northern California Health Care System (US), University of California Davis Medical Center (US), UC Davis Health (US), The Ohio State University (US), University of San Francisco (US), University of California, Davis (US)
AstraZeneca, Mallinckrodt Pharmaceuticals, BeiGene, Incyte, Seagen, Ipsen, National Institutes of Health, Genentech, Daiichi Sankyo Europe
Openalex Percentile: Top 16%
CAR-T cell therapy research
1.05
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