At the 2017 ASH Annual Meeting in Atlanta, GA, Dr. Brian Koffman interviewed Dr. Michael Choi from the University of California in San Diego (UCSD) regarding the utility of HDMP (high dose methylprednisolone) in combination with obinutuzumab for the treatment of CLL.
HDMP is an ultra-high dose steroid therapy that has been studied for the last 10-15 years as an alternative to chemotherapy. This dosing is much, much higher than the doses of steroids used to treat asthma or the autoimmune complications of CLL such as autoimmune hemolytic anemia (AIHA) or immune thrombocytopenic purpura (ITP). Studies have shown the high doses of steroids can rapidly kill tumor cells in patients with CLL. When combined with anti-CD20 antibodies (for example, rituximab), HDMP is associated with high response rates and remissions which can last several years, even in patients with 17p deletion. HDMP can be associated with side effects, including diabetes, serious bone problems, and psychiatric issues. Due to an increased risk of infections with HDMP, patients require concurrent treatment with antibiotics, antifungals, and antiviral agents.
Obinutuzumab is an anti-CD20 antibody that is approved in combination with the chemotherapeutic agent chlorambucil for patients with newly-diagnosed CLL. CD20 is a protein that is expressed on B lymphocytes, which are the cells responsible for CLL. Anti-CD20 antibodies, therefore, target B lymphocytes, resulting in CLL cancer cell death. For more information on how CD20 antibodies works in CLL please see the interview with Dr. Sanjay Sharma from the St. Jude Medical Center published in 2015.
Dr. Januario E. Castro from the USCD Moores Cancer Center reported at ASH 2017 on a study of HDMP in combination with obinutuzumab in patients with CLL. Obinutuzumab is an engineered anti-CD20 antibody, similar to rituximab. When used in combination with chemotherapy, obinutuzumab was shown to be superior to rituximab. Obinutuzumab is current approved by the FDA in combination with chlorambucil in patients with newly-diagnosed CLL.
Take Away Points:
- 41 patients were enrolled in this trial, 21 who had not received any previous treatment and 20 who has relapsed or refractory CLL
- 10% of patients with relapsed or refractory CLL had 17p deletion
- 100% of patients who had not received previous treatment responded to HDMP plus obinutuzumab; 95% of patients with relapsed or refractory CLL also responded
- The median length of time to disease progression was 24.3 months in previously-untreated patients and 15.3 months in patients with relapsed or refractory disease
- Most adverse events were mild with very few infections due to antibiotic treatment.
- Serious adverse events (grade 3 or 4) included neutropenia and thrombocytopenia. Adverse events occurred with less frequency compared to those seen in a study of obinutuzumab and chlorambucil.
HDMP is a steroid that at high doses can rapidly kills tumor cells. Studies with HDMP in combination with antiCD20 antibodies have shown high response rates in patients with CLL. Early trial results of HDMP in combination with obinutuzumab indicate nearly all patients respond to treatment with the majority of adverse events being mild.
The potential advantages of using non-chemotherapy-based treatments includes a reduction of adverse events, often seen with chemotherapy, including myelosuppression, hepatotoxicity, infertility, gastrointestinal toxicity, and secondary malignancies.
More clinical trials are necessary to further elucidate the effectiveness of HDMP in combination with obinutuzumab; however, these early results are encouraging. The potential for another non-chemotherapy option for the treatment of CLL is exciting news for patients with CLL.
Watch the interview with Dr. Choi below or read the transcript here.
Here is the link to the ASH abstract:
Joanne Faysal 4/10/18