Category: Clinical Trials

Venetoclax for CLL Patients Who are Relapsed/Refractory to Ibrutinib or Idelalisib

Furman FaceBy Richard Furman, M.D. 

Patients with CLL who relapse after or become refractory to treatments like ibrutinib or idelalisib have poor outcomes. Venetoclax (also known as ABT-199) is an oral inhibitor of the BCL-2 (B-cell lymphoma 2) protein. The BCL-2 protein plays a critical role in preventing cells from undergoing apoptosis (cell death), in healthy cells and in CLL cells. In a recent study presented at the 2016 annual ASH meeting, we evaluated the effectiveness of venetoclax in treating people who relapsed after or were refractory to ibrutinib or idelalisib.

During this phase 2 trial 64 people with CLL were divided into two arms. The first arm consisted of those who were relapsed or refractory to ibrutinib, while the second arm included those who were relapsed or refractory to idelalisib. 43 patients were enrolled in the first arm and were on ibrutinib for a median of 17 months, receiving venetoclax for a median of 13 months, while 21 patients in the second arm were on idelalisib for a median of 8 months and received venetoclax for a median of 9 months. Thirty-nine patients in the ibrutinib arm and 21 patients in idelalisib arm completed the full course of treatment. The objective response rate as determined by investigators was 69% (27/39) for people who were ibrutinib resistant, and 57% (12/21) for the idelalisib resistant. At the time of analysis no median progression free survival or overall survival has been reached. Overall the progression free survival was 72% and overall survival was 90% for all participants.

The results from this trial demonstrate that venetoclax has displayed robust activity and is tolerable for people whose CLL has progressed after treatment with ibrutinib and idelalisib. Although there have been few complete responses, patients will continue to be monitored to chart any further improvements. Additional follow up will be required to assess how long lasting venetoclax responses will be.

Dr. John Leonard Discusses CHOP Versus DA-EPOCH-R for the Use of Untreated Diffuse Large B-Cell Lymphoma

jl-healio

In an interview during the 2016 American Society of Hematology Annual Meeting, Dr. John Leonard discusses results from a phase III trial where researchers compared the treatments R-CHOP to DA-EPOCH-R in DLBCL patients specifically from either the GCB or ABC subtypes.

A full link to the video of Dr. Leonard discussing the trial can be found by clicking above or be seen on Healio.com.

FAT1 Mutations Influence Time to First Treatment in Untreated CLL

john-allan-mdBy John Allan, M.D.

Despite recent strides in mapping the mutational landscape of chronic lymphocytic leukemia (CLL) there is still limited information regarding the clinical impact of some less common gene mutations in the treatment of CLL. As next generation sequencing (NGS) has become more readily available physicians have more information about their patient’s genome, but this information is often lacking in context.

Using a commercially available NGS platform researchers from Weill Cornell Medicine identified a high prevalence of mutations in the FAT1 gene in people with CLL. FAT1 plays a role in regulating WNT signaling and tumor suppression and mutations have previously been associated with leukemia. Given the prevalence of FAT1 mutations in our CLL database and evidence suggesting FAT1 contributes to tumor growth, researchers investigated the clinical impact of FAT1 mutations.

Altogether 172 patients were included in the study. Nineteen (11%) patients were found to have a FAT1 mutation and 153 (89%) were lacking the mutation. In total 21 mutations were identified with 17 being unique. No significant differences were found between groups based on age or co-occurrence of high risk mutations, although 17p deletions occurred significantly more in mutated FAT1 patients (24%) compared to people lacking the mutation (7%). Mutated FAT1 patients had a significantly shorter TTFT at 50 months compared to 143 months for people lacking the mutation.

Researchers identified a higher prevalence of FAT1 mutations in untreated CLL patients than previously reported. FAT1 was found to associate with the 17p deletion, but no other high-risk mutations. We also found a vast difference in TTFT between mutated FAT1 and those lacking the mutation, although there was no difference in response rates when treated with novel agents.

These findings suggest that FAT1 mutations may be more common in patients, who have yet to receive treatment than commonly supposed. Results warrant additional research to investigate the influence of FAT1 mutations and association with the 17p deletion.