Ofatumumab Approved for Use in Combination with Fludarabine and Cyclophosphamide to Treat Patients with Relapsed CLL

The Backstory

Last month, the FDA approved the use of ofatumumab in combination with fludarabine and cyclophosphamide to treat patients with relapsed chronic lymphocytic leukemia (CLL).

This is the 4th FDA approval received by ofatumumab for the treatment of patients with CLL. Ofatumumab was initially approved in 2009 for the treatment of patients with CLL who are refractory to fludarabine and alemtuzumab, and subsequently approved in April 2014 for use in combination with chlorambucil for previously untreated patients with CLL. In January 2016 ofatumumab was approved for the treatment of patients with recurrent or progressive chronic lymphocytic leukemia (CLL) who are in complete or partial response following at least two prior treatment therapies.

What is ofatumumab?

Ofatumumab is a human monoclonal antibody designed to target the CD20 molecules found on the surface of CLL cells and B-cell lymphocytes. CD20 molecules are found in over 90% of B-cell lymphomas. Ofatumumab is an immunotherapy that works by attaching itself to the CD20 molecule found on the surface of B-cells and directs the immune system to kill the cancerous B-cells.

Why was ofatumumab granted FDA approval?

The latest approval for ofatumumab was based on improved progression free survival (PFS) results in the phase III COMPLEMENT-2 study. PFS refers to the length of time following the course of treatment, that a patient’s disease does not get worse, or progress. In this study the median PFS of ofatumumab combined with chemotherapy was 28.9 months compared to 18.8 months for only the fludarabine and cyclophosphamide combination.

Were there any side effects?

Side effects were similar to the side effects found in previous trials. They included infusion reactions, neutropenia, thrombocytopenia, anemia, nausea, leukopenia, vomiting, pyrexia, rash, fatigue, and pneumonia.

How can you access ofatumumab now?

While all available WCM trials with ofatumumab for people with CLL have recently closed, our understanding of how best to use ofatumumab continues to increase. You can look to this space for further updates on CLL trials examining the use of ofatumumab.

A full list of trials open at WCM for patients with CLL is available on our Joint Clinical Trials website.

Venetoclax for the Treatment of CLL Patients who have Relapsed after or are Refractory to Ibrutinib/Idelalisib


By Richard Furman, M.D.

CLL patients who relapse after or are refractory to ibrutinib or idelalisib often have few treatment options and poor outcomes. In an ongoing phase II study, presented at the 2016 annual ASCO meeting, researchers investigated the activity of venetoclax in patients with CLL who have relapsed or become refractory to ibrutinib or idelalisib. Venetoclax (Venclexta, ABT-199), is the first FDA-approves treatment that inhibits the BCL-2 (B-cell lymphoma 2) protein. The BCL-2 protein plays an important role in enabling CLL cells to survive. CLL cells and other lymphomas over express and are more dependent upon BCL-2 protein than normal cells. Therefore, when venetoclax inhibits the protein, the CLL cells die, while the normal cells continue unharmed.

54 patients were enrolled into the two arms of the trial based upon whether they were relapsed or refractory to ibrutinib (Arm A, 38 patients) or idelalisib (Arm B, 10 patients). 48 patients were evaluable for responses. The overall response rate for ibrutinib treated patients was 61% (CR=8%; PR=53%) and for idelalisib was 50% (CR=0%; PR=50%). Side effects were found in less than 20% of patients with the most common including neutropenia, diarrhea, nausea, anemia, fatigue, and hypophosphatemia. These results show that venetoclax displays promising activity for CLL patients who have relapsed or are refractory to both ibrutinib and idelalisib and can be safely administered.

Further research is required to demonstrate the depth and duration of response, but these initial results are positive.

Effectiveness of Ibrutinib Treatment in Patients with Relapsed or Refractory CLL/SLL with del17p

Dr. Richard Furman
Dr. Richard Furman

CLL patients with a deletion of chromosome 17p on iFISH demonstrate an aggressive course with rapid disease progression and resistance to chemotherapy. The 17p status had been previously confirmed by iFish a test that examines individual cells for chromosomal changes that are significant in predicting disease outcome The missing portion  of chromosome 17 contains the gene for p53, which is one of the most important tumor suppressor genes. The Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib has demonstrated efficacy for patients with the del17p and been approved by the FDA.

In this trial, CLL patients with del17p received ibrutinib once daily until disease progression or unacceptable toxicity.  63% of patients were Rai stage III or IV and 39% had received ≥3 prior therapies. At the median follow-up of 11.5 months, the overall response rate  for all patients was 83%, with a 12 month progression free survival and overall survival  of 79% and 84% respectively.

These results provide further evidence of ibrutinib’s efficacy in prolonging the survival of high risk patients. For more information about available trials for CLL/SLL at Weill Cornell Medicine please follow the link to our new clinical trials listing.

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