Hairy Cell Leukemia: Making an Impact...

About 2.5 years ago, I blogged regarding a new drug I read about and brought to the attention of the Hairy Cell Consortium.  It's a Bruton's Tyrosine Kinase (BTK) inhibitor known as PCI-32765, and was inspired by a rare disease known as XLA, in which the body doesn't produce B-cells due to a BTK gene defect.  Developed to treat NHL, when I read about it, I thought the underlying mechanism warranted investigation for treating HCL.

Here's a link to the post:

http://jonshclblog.blogspot.com/2010/11/i-want-new-drug.html

Well, the email describing the mechanisms and potential of the drug that I sent to the Hairy Cell Consortium had an impact.  They performed in vitro studies of the drug, and it was found to be highly effective in stopping HCL proliferation!

http://files.shareholder.com/downloads/PCYC/0x0x620800/0228F1DA-BFD9-4E43-9CD4-3688E1ECB36A/SAT_Poster_HCL-ASH2012_Sivina_FINAL_Dec_3_APPROVED.pdf

Clinical trials using this drug to treat relapsed and refractory Hairy Cell Leukemia patients are now underway at The Ohio State University Medical Center (Go Buckeyes!!!) and The Karmanos Cancer Institute in Detroit Michigan!

http://www.clinicaltrials.gov/ct2/show/NCT01841723?term=Hairy+Cell+Leukemia&rank=4

The drug goes by the trade name Ibrutinib.  Let's hope it lives up to the potential I anticipated in my post back in 2010!  Seems like our arsenal and options are really piling up.  Translational medicine and targeted therapies are taking off, and will hopefully make chemo a distant memory someday soon. 

On a personal note:    Back in April, I went on a 5 day trek to the Royal Arch Loop of the Grand Canyon South Rim with some friends from work.  It was awesome!  The second to last day we hiked 13 hours in 80 degree weather and ran out of water, so we banded a team of 5 together for a 3-hour night hike down to the Colorado River to collect 40 liters of water for the rest of the team (9 of us altogether), so we could hike out the next day.  Awesome!  5 years ago, I couldn't climb 13 steps without stopping to catch my breath.  The last day of the Royal Arch trek, I hiked 4000 feet vertically with 32 pounds on my back for over 7 miles and felt fantastic!!!

I go for my annual re-staging at NCI/NIH on June 26th.  Wish me luck...

Elves' Chasm

Rappelling down a canyon wall

The Ravine to Royal Arch Creek

The Royal Arch!

Desert Blossom

Toltec Beach on The Colorado River

Night Hike and Water Filtering Mission

Hairy Cell Leukemia: I Want a New Drug ...

I want a new drug... 

Okay, maybe not yet, but it looks like there are lots of new potential candidates for treating HCL that still have yet to be explored.  Two posts ago, I mentioned a new third-generation antibody that has the potential of being 5 to 100 times more powerful than Rituxan but hasn't been used to treat HCL yet.  I'm hoping some preliminary in-vitro studies will be conducted soon.

Today, I found another one -- a Btk (Bruton's tyrosine kinase) Inhibitor, PCI-32765, that is currently in Phase I clinical trials in patients with B cell malignancies (specifically Non-Hodgkin's Lymphoma).  Btk is an essential signalling factor needed for the development of  B-cells.  By inhibiting it, the Btk protein production is blocked and B-cells can't develop.  The inspiration for developing the drug was born from a disease, XLA, in which B-cells are absent from the peripheral blood because Btk is not produced due to a Btk gene defect. 

What's great about this drug is that it's a pill, taken orally, that inhibits Btk production and thus B-cell production.  Since HCL is a B-cell malignancy, I've asked the Hairy Cell Consortium if they are familiar with the drug and whether it may be a candidate for a Phase 1 trial to treat relapsed and refractory HCL patients.  I'll let you know if they respond. 

"This is a very selective compound for B-cells, and it could represent an important alternative to rituximab therapy for the treatment of B-cell NHL. Other obvious applications include autoimmune disorders such as rheumatoid arthritis and lupus, and Pharmacyclics also has strong preclinical efficacy with PCI-32765 in these disease models," said Dr. Mark Genovese, Professor of Medicine and Co-Chief of the Division of Immunology and Rheumatology at Stanford University Medical Center and member of Pharmacyclics' Scientific Advisory Board. [Taken from Pharmacyclics Press Release dated April 13, 2009]


Wouldn't it be great if we HCL'ers could knock out minimal residual disease (MRD) and then take a pill as maintenance therapy so that we'd never have to worry about it ever coming back?  Even better if it could act as the first-line therapy someday and eliminate the need for chemotherapy altogether (and side-effects like increased secondary cancer risk and impact to T-cell counts), or provide  a new treatment alternative for patients with HCL-V (the variant form of HCL that doesn't respond as well to Cladribine).