Ofatumumab, Methylprednisone, Lenalidomide Regimen Feasible as Frontline Therapy in CLL/SLL

New long-term phase 2 data show the combination of ofatumumab (Kesimpta; Novartis), high-dose methylprednisolone (HDMP), and lenalidomide (Revlimid; Celgene) is effective and relatively safe as a frontline treatment for patients with chronic lymphocytic leukemia (CLL) and small lymphocytic leukemia (SLL).

White blood cells | Image credit: Sebastian Kaulitzki - stock.adobe.com

The report, which followed some patients for more than 5 years, was published in the journal Clinical Lymphoma, Myeloma, & Leukemia.

Corresponding author Eva Sahakian, PhD, of the H. Lee Moffitt Cancer Center and Research Institute, and colleagues explained that despite the current incurability of CLL, a growing number of useful treatments are available. Chemoimmunotherapy has historically been the go-to frontline therapy, but they said newer, less-toxic agents are increasingly being used, particularly in patients who are young and fit.

Ofatumumab is a fully humanized monoclonal antibody (mAb) to CD20 and has been approved in the US to treat relapsing multiple sclerosis (MS). However, Sahakian and colleagues said previous research has shown it to be a feasible therapy in combination with lenalidomide for patients with relapsed or refractory CLL.

“Furthermore, the combination of high-dose methylprednisolone with a mAb has shown favorable use for managing this disease,” they wrote. “On the basis of these data, we hypothesized that the combination of HDMP and ofatumumab as a debulking strategy, followed by ofatumumab therapy plus lenalidomide, would be an active and safe regimen as a frontline regimen for CLL.”

To test their hypothesis, the investigators recruited 45 patients with treatment-naive CLL/SLL and began them on the above treatment regimen. The patients had a median age of 62.6 years, but they ranged in age from 48 to 86 years old. Many of the patients had high-risk features, including del17p (18%), Del11q (22%), and unmutated IGHV genes (76%).

The median duration of treatment was 32.2 months, and most patients (n = 36) discontinued their treatment. The most common reasons were adverse events (AEs; 40%) disease progression (22%), allogeneic hematopoietic cell transplantation (7%), and secondary malignancies (7%).

In terms of safety, the investigators said treatment-related hematological AEs were among the most common AEs. Most notably, 69% of participants reported grade 3 or 4 neutropenia. Eleven percent of patients reported grade 3 or 4 thrombocytopenia, and 2% of patients reported grade 3 or 4 anemia.

Infectious complications were also common, with 58% of patients experiencing grade 1 or 2 infections, and 9% of patients experiencing grade 3 or 4 infections, including severe sepsis.

In terms of long-term efficacy, at a median follow-up of 61.7 months, 9 patients remained on the regimen. The best overall response rate came at 36 months, when there was a 96% overall response rate among the 24 patients continuing on the therapy. That same time point had the highest complete response rate, 29%.

Though the investigators said their study supported the use of this regimen in some patients, they also noted that more recent advances could limit the regimen’s use. In particular, they said the role of lenalidomide in the current era is less clear in light of the approval of therapies such as venetoclax (Venclexta; Abbvie/Genentech) to treat CLL.

“Frontline BTK inhibitors and venetoclax-based therapies remain as standard frontline approaches given their sustained clinical efficacy and survival benefit,” they said.

Sahakian and colleagues concluded that their data suggest that ofatumumab, HDMP, and lenalidomide are a feasible alternative treatment option for treatment-naive patients, although treatment options continue to evolve and the best course for a particular patient will depend on a number of different factors.

Reference

Chavez JC, Grajales A, Sandoval-Sus J, et al. 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. Published online February 13, 2024. doi:10.1016/j.clml.2024.02.001