Ofatumumab plus high dose methylprednisolone followed by ofatumumab plus alemtuzumab to achieve maximal cytoreduction prior to allogeneic transplantation for 17p deleted or TP53 mutated chronic lymphocytic leukemia^*

* Presented in part at the 2015 American Society of Hematology Annual Meeting, Orlando, FL, December 5–8, 2015

Abstract

We hypothesized that ofatumumab with sequential methylprednisolone – alemtuzumab would be an effective and tolerable regimen for patients with high-risk chronic lymphocytic leukemia (CLL) with TP53 dysfunction. Thirty CLL patients with TP53 dysfunction (15 treatment naive (TN), 15 relapsed/refractory (R/R)) were enrolled in this phase II study. Therapy included ofatumumab with methylprednisolone for 2–4 monthly cycles, then ofatumumab with alemtuzumab for 4–24 weeks, then allogeneic transplantation or maintenance. The rate of overall response, complete response, marrow minimal residual disease (MRD) negativity, 3-year progression-free survival and overall survival were 80, 13, 80, 53, and 66%, respectively, in TN patients and 68, 0, 54, 25, and 53%, respectively, in R/R patients. Notable grade 3/4 toxicities included neutropenia and infection in 43 and 40% of patients, respectively. At median follow-up of 45 months, 13 patients died, and 10 patients are alive posttransplant. Overall, we observed high rates of MRD-negativity and acceptable tolerability in high-risk CLL.

Keywords:

• CLL
• deletion 17p
• TP53
• MRD
• alloHSCT

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online at https://doi.org/10.1080/10428194.2018.1519814.

Additional information

Funding

The authors acknowledge the patients and their caregivers for their participation in this trial, as well as funding through a cooperation between the National Comprehensive Cancer Network (NCCN) and Glaxo-Smith-Kline (GSK). This work was also supported by Novartis Pharma.