• Lenalidomide, obintuzumab, and CHOP chemotherapy is an efficacious and well tolerated treatment for newly diagnosed DLBCL

  • LO-CHOP led to high molecular response rates by circulating tumor DNA sequencing during and after treatment in this phase Ib/II study

Diffuse large B-cell lymphoma (DLBCL) can be cured with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone immunochemotherapy (R-CHOP), but a third of patients experience refractory or relapsed disease after frontline R-CHOP. Randomized studies comparing R-CHOP with modified regimens replacing R with obinutuzumab (O) or adding lenalidomide (L) to R-CHOP have not resulted in improved outcomes, but the combination of L and O may enhance NK-cell mediated antibody dependent cellular toxicity when paired with CHOP. Here, we report on long term outcomes of a phase Ib/II study (NCT02529852) where 53 patients with newly diagnosed DLBCL received 6 cycles of LO-CHOP. End of treatment overall and complete response rates in the 50 evaluable patients were 98% and 90%, respectively. After a median follow up of 4.5 years, 4-year progression free and overall survival rates were 87.4% and 91.3%. Grade 3-4 adverse events were experienced by 70% of patients and included neutropenia (38%), thrombocytopenia (17%), fatigue (13%), neutropenic fever (13%), and infection (9%). Of 33 patients profiled with circulating tumor DNA (ctDNA) sequencing, 31 (94%) had detectable pre-treatment ctDNA with CAPP-Seq, 24/31 (77%) were classifiable by LymphGen classifier, and 15/20 (75%) and 12/17 (71%) patients achieved early and major molecular responses after 1 and 2 cycles, respectively. Using PhasED-Seq, 16/18 evaluable patients (89%) had no detectable ctDNA after at least 5 cycles of LO-CHOP. LO-CHOP demonstrates high efficacy and tolerability in newly diagnosed DLBCL, leading to a high rate of undetectable minimal residual disease by ctDNA by end of therapy. This trial is registered at www.clinicaltrials.gov as NCT02529852.

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