A phase 2 clinical trial showed that ofatumumab with methylprednisolone followed by ofatumumab with alemtuzumab achieved a high rate of minimal residual disease (MRD) negativity as well as acceptable tolerability among patients with high-risk chronic lymphocytic leukemia (CLL).1 Trial results were published online October 15, 2018, in Leukemia & Lymphoma.
A total of 30 patients with CLL and TP53 dysfunction were enrolled in the trial between December 2011 and May 2014. Half of the patients were treatment-naive, and half had a relapsed/refractory status. Patients underwent 2 to 4 monthly cycles of ofatumumab with methylprednisolone followed by 4 to 24 weeks of ofatumumab with alemtuzumab. Then, patients underwent allogeneic hematopoietic stem cell transplantation (alloHSCT) or maintenance.
For treatment-naive patients, overall response was 80%, complete response was 13%, MRD negativity was 80%, 3-year progression-free survival was 53%, and overall survival was 66%. For relapsed/refractory patients, overall response was 68%, complete response was 0%, MRD negativity was 54%, 3-year progression-free survival was 25%, and overall survival was 53%. Common grade 3 and grade 4 toxicities were neutropenia and infection. Ten patients are still alive after alloHSCT at a median follow-up of 45 months.
“In summary, our regimen induced a high rate of MRD negativity in TP53-deleted CLL, thereby allowing many patients to move on to alloHSCT with maximal cytoreduction,” the study authors wrote. “Our findings support the use of this regimen for selected patients with high-risk CLL who seek to undergo alloHSCT with the goal of long-term disease-free survival.”
Disclosure: The work was funded in part by pharmaceutical companies. For a full list of disclosures, please refer to the original study.
- Davids MS, Kim HT, Yu L, et al. 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 [published online October 15, 2018]. Leuk Lymphoma. doi: 10.1080/10428194.2018.1519814