Long-term follow up of the combination of ofatumumab, high-dose methylprednisolone, and lenalidomide for untreated chronic lymphocytic leukemia with biomarker analysis

Julio C Chavez; Ariel Grajales; Jose Sandoval-Sus; Elyce Turba; Lisa Nodzon; Angimar Uriepero-Palma; Mohammad Ammad-Ud-Din; Eva Sahakian; Rami Komrokji; Lubomir Sokol; Frederick L Locke; Bijal Shah; Jeffrey Lancet; Eduardo M Sotomayor; Mohamed A Kharfan-Dabaja; Celeste Bello; Javier Pinilla-Ibarz

doi:10.1016/j.clml.2024.02.001

Long-term follow up of the combination of ofatumumab, high-dose methylprednisolone, and lenalidomide for untreated chronic lymphocytic leukemia with biomarker analysis

Clin Lymphoma Myeloma Leuk. 2024 Feb 13:S2152-2650(24)00060-0. doi: 10.1016/j.clml.2024.02.001. Online ahead of print.

Authors

Julio C Chavez¹, Ariel Grajales², Jose Sandoval-Sus³, Elyce Turba¹, Lisa Nodzon¹, Angimar Uriepero-Palma⁴, Mohammad Ammad-Ud-Din¹, Eva Sahakian⁵, Rami Komrokji¹, Lubomir Sokol¹, Frederick L Locke⁶, Bijal Shah¹, Jeffrey Lancet¹, Eduardo M Sotomayor⁷, Mohamed A Kharfan-Dabaja⁸, Celeste Bello¹, Javier Pinilla-Ibarz⁴

Affiliations

¹ Department of Malignant Hematology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
² Department of Immunology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
³ Department of Medicine, University of South Florida, Tampa, FL, USA.
⁴ Department of Malignant Hematology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA; Department of Immunology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
⁵ Department of Malignant Hematology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA; Department of Immunology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA. Electronic address: eva.sahakian@moffitt.org.
⁶ Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
⁷ Tampa General Cancer Institute, Tampa FL.
⁸ Division of Bone Marrow Transplantation, Mayo Clinic, Jacksonville, FL, USA.

PMID: 38508880
DOI: 10.1016/j.clml.2024.02.001

Abstract

Background: Advancements in frontline therapy and chemotherapy-sparing treatments in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) have altered the treatment algorithms of this disease. We present a frontline alternative for treatment- naïve (TN) CLL/SLL patients.

Methods: This was a single-center, phase 2 study of high-dose methylprednisolone (HDMP) and ofatumumab with lenalidomide and ofatumumab consolidative therapy for all comers with TN CLL/SLL. Treatment was continued until disease progression or intolerable side effects. Patients were assessed for response per iwCLL 2008 criteria after completing cycles 3 and 12.

Results: Forty-five patients were enrolled (median age, 62.6 years). High-risk features included del17p (18%), Del11q (22%), and unmutated IGHV gene (76%). Median treatment duration was 32·2 (2·7-75·9) months. Thirty-six patients discontinued treatment due to disease progression (22%), adverse events (40%), allogeneic hematopoietic cell transplantation (allo-HCT) (7%), consent withdrawal (4%), and secondary malignancies (7%). The best overall and complete response rates were 96& and 29% respectively. At median follow-up of 61·7 (5·6-84·9) months, 9 patients remained on treatment. Median progression-free survival was 54·4 (2·9-77·6) months. Three patients underwent allo-HCT after a median of 3 (3-4) treatment cycles. Treatment was well tolerated, with a grade 3/4 infusion reaction in one patient. The most common grade 3/4 hematological adverse event was neutropenia (69%). Four patients had grade 3/4 infections. No grade 3/4 tumor flares, tumor lysis syndrome, or thrombosis were observed.

Conclusion: The combination of ofatumumab, HDMP, and lenalidomide was effective and relatively well tolerated in treatment-naive CLL/SLL. Its role in the frontline setting remains unclear given the current available and effective treatment options.

Funding: The funders had no role in the study.

Keywords: Lenalidomide; chronic lymphocytic leukemia; high dose steroids; immunotherapy; ofatumumab.