Adding Umbralisib and Ublituximab (U2) to Ibrutinib in Patients with CLL: A Phase II Study of an MRD-Driven Approach

Autor: Lindsey E. Roeker, Tatyana A. Feldman, Jacob D. Soumerai, Victoria Falco, Gail Panton, Colleen Dorsey, Andrew D. Zelenetz, Lorenzo Falchi, Jae H. Park, David J. Straus, Camila Pena Velasquez, Sonia Lebowitz, Yehudit Fox, Kristen Battiato, Carissa Laudati, Meghan C. Thompson, Elizabeth McCarthy, Sabrina Kdiry, Rosalba Martignetti, Teja Turpuseema, Michelle Purdom, Dana Paskalis, Hari P. Miskin, Peter Sportelli, Lori A. Leslie, Anthony R. Mato
Rok vydání: 2022
Předmět:
Zdroj: Clinical Cancer Research. 28:3958-3964
ISSN: 1557-3265
1078-0432
DOI: 10.1158/1078-0432.ccr-22-0964
Popis: Purpose: Ibrutinib has transformed the management of chronic lymphocytic leukemia (CLL), though its use is limited by toxicity and resistance. In this study, we utilized an “add on” approach for patients who had been treated with ibrutinib in the front-line or relapsed/refractory settings with detectable MRD. Umbralisib and ublituximab (U2) were added on to ibrutinib, patients were treated until achieving undetectable-MRD (U-MRD), and then they entered a period of treatment-free observation (TFO). Patients and Methods: Patients were eligible if they received ibrutinib in any line of therapy for at least 6 months and had detectable MRD (flow cytometry, Results: Twenty-eight patients were enrolled of whom 27 were evaluable for efficacy. Patients received ibrutinib for a median of 21 months (range 7–67) prior to study enrollment. Fourteen patients (52%) have achieved U-MRD per protocol whereas 78% had at least one U-MRD evaluation. Seventeen patients (63%) have entered TFO after a median of 6.4 months on triplet therapy. Progression-free survival at 12 months was estimated at 95%. Grade ≥3 adverse events were hypertension 7%, diarrhea 4%, and increased ALT/AST 4%. Conclusions: This triplet approach utilizes the addition of U2 to ibrutinib as an MRD-driven time-limited therapy. This therapy was well tolerated and effective. TFO following this therapy appears durable in ongoing follow-up.
Databáze: OpenAIRE
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