Lenalidomide and obinutuzumab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) demonstrates promising efficacy and tolerability in newly diagnosed diffuse large B-cell lymphoma (DLBCL), yielding a high rate of undetectable minimal residual disease (MRD) by circulating tumor DNA (ctDNA), according to a study presented at the 2022 ASCO Annual Meeting.

This single-center phase 1b/2 study enrolled patients with previously untreated CD20-positive DLBCL. Patients received 6 cycles of CHOP with intravenous (IV) obinutuzumab 1000 mg on days 1, 8, and 15 during cycle 1 and day 1 during cycles 2 to 6, and oral lenalidomide on days 1 to 14 of each cycle.

The primary aims of the study were to determine the maximum tolerated dose of lenalidomide and evaluate the efficacy of lenalidomide and obinutuzumab with CHOP. Researchers collected plasma sample for ctDNA analysis.

A total of 53 patients were enrolled, 6 in the phase 1b portion of the study and 47 in the phase 2 portion. At a maximum tolerated dose of lenalidomide at 15 mg, no patients experienced dose-limiting toxicities.

There were 50 evaluable patients, 49 (98%) experienced an overall response and 45 (90%) experienced a complete response. The median follow-up was 4.5 years. The 4-year progression-free survival was 87.4% and overall survival was 91.3%.

Any grade adverse events (AEs) were reported by 100% of patients and grade 3 to 4 AEs were reported in 70% of patients. Grade 3 to 4 AEs included neutropenia (38%), thrombocytopenia (17%), fatigue (13%), neutropenic fever (13%), and infection (9%). In total, 4 patients developed venous thromboembolism.

At baseline, 31 (94%) of 33 patients had detectable ctDNA with CAPP-Seq. Of these patients, 24% had high ctDNA ( > log 2.5 hGe/ml) and 24 (77%) were evaluable by LymphGen classifier. The molecular subtypes included EZB (n = 5, 21%), ST2 (n = 5, 21%), MCD (n = 4, 17%), and other (n = 9, 38%). All 5 patients with EZB and 4 of the 5 patients with ST2 were germinal center subtype while 2 of 4 patients with MCD pts were non-germinal center subtype.

Of those who received lenalidomide and obinutuzumab plus CHOP, 13 (72%) of 18 patients achieved early response and 11 (73%) of 15 patients achieved a major molecular response. Overall, 16 (89%) of 18 patients had no detectable ctDNA after ≥5 cycles of lenalidomide and obinutuzumab plus CHOP, by PhasED-Seq.

“[Lenalidomide and obinutuzumab plus CHOP] demonstrates high efficacy and tolerability in newly diagnosed DLBCL, leading to a high rate of undetectable [MRD] by ctDNA,” concluded Hua-Jay Jeffery Cherng, MD, MD Anderson Cancer Center, Houston, and colleagues.

“Noninvasive molecular subtyping is feasible as a supplement to tissue diagnosis and should be incorporated in future studies aiming to improve on RCHOP,” they added.

Source:

Cherng HJ, Alig S, Oki Y, et al. Long-term outcomes and circulating tumor DNA analysis from a phase I/II study of lenalidomide and obinutuzumab with CHOP for newly diagnosed diffuse large B-cell lymphoma. Presented at: ASCO Annual Meeting; June 3-7, 2022. Chicago, IL; and virtual. Abstract 7553.