My husband Carl and I met with Dr. Michael Choi, a researcher in The Thomas Kipps laboratory at the Moores Cancer Center at the University of California – San Diego in La Jolla. We discussed some of the clinical trials and options for CLL/SLL cancer patients who have relapsed. We also discussed some of the unknowns.
RECENT RESEARCH:
Recent worldwide cancer therapy research has focused on
• targeted therapies
(i.e. ibrutinib, idelalisib):
Ibrutinib was FDA-approved July 2014 as a frontline
treatment for 17p deleted CLL/SLL patients. Infinity Pi3K oral inhibitor drug
(idelalisib) was FDA approved July 2014 for relapsed CLL, follicular lymphoma
and small lymphocytic lymphoma (SLL). Inhibitor oral cancer drugs are
successfully tolerated for the most part; however, these targeted therapies
developed to attack only cancer cells still have an effect on other body
tissues, often leaving the body subject to infections and low immunoglobulin
levels.
• monoclonal
antibodies (i.e. rituximab, obinutuzumab, ofatumumab):
According to Dr. Choi, Gazyva (obinutuzumab) is superior to rituximab
and is a new agent. It was FDA approved November 2013. Arzerra (ofatumumab)
received FDA approval to treat CLL April 2014. These monoclonal antibodies also
have an effect on other body tissues, often causing infections and low
immunoglobulin levels.
• targeted chimeric
antigen receptor T-cell (CART) treatments:
This cancer treatment, which is in clinical trial, has cured
a number of leukemia patients, but it has left them with no healthy B-cells,
since the treatment wipes out all B-cells. This means the patients must have
monthly blood infusions. Researchers are continuing to figure out a way to target
only leukemic B-cells.
UNKNOWNS:
One of the unknowns in the CLL research community includes
what to do when ibrutinib stops working. Does the patient move to another
kinase inhibitor (i.e. ABT-199, IPI-145)? Are monoclonal antibodies combined
with the kinase inhibitors? What are the long-term side effects of continuing
to use a drug after the patient has reached clinical complete remission? Can a
patient safely stop or does the cancer return full force?
UCSD CANCER LAB
TRIALS:
I was particularly interested in the ABT-199 and ROR-1
clinical trials at UCSD. There are a number of ABT-199 clinical trials in
Phases 1b to 3 alone and in combination with monoclonal antibodies at UCSD.
Lots of possibilities.
The ROR-1 clinical trial at UCSD is in the early stage of
research. The researchers at the Moores Cancer Center have been working on
addressing the goal of specific leukemic cell targeting without harming other
body tissues. The researchers discovered
that a protein called ROR-1 is found on leukemic cells, but not found on normal
B-cells or other normal body tissues. ROR-1 is also expressed in other cancers.
A monoclonal antibody named Cirmtuzumab (a.k.a. UC-961) was found to bind to
ROR-1 in preclinical tests with laboratory mice without any apparent toxicity.
June 2014 the FDA gave the go-ahead to experiment on relapsed or refractory CLL
patients in a Phase 1 clinical trial to determine safety, optimal dose, and
whether it is tolerable. Patients will be infused intravenously every two weeks
for two months. The experiment will continue based on safety and effectiveness.
Even though this clinical trial is in the early stages of
blood cancer treatment, it could have a profound effect on all cancers. Blood cancer
research is leading the way for the cure of all cancers. It is a good day.
