Immunochemotherapy combining lenalidomide and obinutuzumab with cyclophosphamide, doxorubicin, vincristine, and prednisone (LO-CHOP) appears to have high efficacy in the treatment of newly diagnosed diffuse large B-cell lymphoma (DLBCL), according to a recently published study in Blood Advances.

Currently, the immunochemotherapy regimen of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) constitutes the mainstay of therapy for patients with DLBCL. However, approximately 33% of patients have poor responses to this regimen, Hua-Jay Jeffery Cherng, of the Columbia University Medical Center in New York, and colleagues noted.

Although previous studies that assessed the efficacy of lenalidomide and obinutuzumab individually showed discouraging results, findings from the GALEN study suggested that the combination of the 2 drugs could have a synergistic effect, the researchers added.

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“Patients treated with the combination experienced activation of [natural killer (NK)] cells and reversal of an immature NK cell phenotype as determined by cell surface markers,” the authors wrote.

Taking into account these findings, the authors hypothesized that LO-CHOP could have high efficacy and tolerability in patients with recently diagnosed DLBCL. The open-label, single-arm phase 1b/2 study aimed to assess the efficacy and tolerability of LO-CHOP in a cohort of 53 patients with confirmed DLBCL diagnosis. All patients had recently been diagnosed with the disease and were scheduled to receive 6 cycles of LO-CHOP.

Efficacy was measured through overall response rate (ORR) and complete response rate (CRR) with imaging. Safety was defined as the absence of unmanageable grade 3 nonhematologic adverse effects. 

At the end of therapy, ORR was 98%, and CRR was 90%, only 1 patient experienced progressive disease. After 54 months of median follow-up time, 6 patients had disease progression, and 4 died. The overall survival rate at the end of the follow-up period was 81%.

Regarding safety, over 70% of patients experienced a grade 3 or 4 adverse effect. However, there were no fatal adverse effects. The most common adverse effects included fatigue, anemia, myalgia, and constipation. The most common grade 3 adverse effect included neutropenia followed by thrombocytopenia and febrile neutropenia.

“In summary, LO-CHOP as a modified frontline regimen for DLBCL in this single-arm phase 1b/2 study had high rates of radiographic and molecular response, durable remissions with long-term follow-up, and an expected safety profile,” the authors concluded.

Reference

Cherng H, Alig S, Oki Y, et al. A phase 1/2 study of lenalidomide and obinutuzumab with CHOP for newly diagnosed DLBCL. Blood Adv. Published online November 11, 2022. doi:10.1182/bloodadvances.2022008174