nanotech detection of minimal residual disease (MRD)

[Guest guest]

Thank you, Liz, for sharing this important development that hopefully will

address an URGENT UNMET NEED –

… how to know if therapy was successful or not and how much treatment is

sufficient to meet the goal of enjoying a durable remission and possible cure?

Presently we complete therapy based on average outcomes in trials, the protocol

based often on the maximum tolerated dose and cumulative toxicities (CHOP-R x 6,

or FCR x 6).

… Then we use imaging to measure responses of tumors (knowing that individual

tumor cells are too small to see with CT or PET).

… So we image repeatedly ... and in clinical trials we image often in order

to measure time to relapse " events, " so we can compare one therapy to another

for groups (not individuals) ... based on when the disease comes back.

This to guide clinical practice for others based on average outcomes ... All of

this imprecise group information can take many years to assess – and for the

indolent lymphomas providing very, very, weak evidence for comparative

effectiveness in respect to survival – which is the true measure of success.

But this is not how it's done AIDS!

From the ODAC AA meeting:

" Accelerated approval [for AIDS/HIV] was based on short-term viral load changes

at 24 weeks, with confirmation of a durable viral load suppression at 48 weeks,

and we looked for concordance with other markers, as well.

So the typical accelerated approval study design, really post this validation

process and pre, has been a randomized, placebo-controlled, usually two-armed

study, sometimes more if there's multiple doses studied, in patients who have

failed multiple drug regimens but usually have maybe one or two drugs left.

So arm one would consist of a new regimen of optimized therapy with approved

drugs, and arm two is optimized therapy plus the investigational drug. And if

viral suppression does not occur or occurs and rebounds, then the patient is

considered a virologic non-responder, and they can exit the trial [helping

enrollment too].

So the patients liked this, clinicians liked it, statisticians liked it,

everybody was happy.

So that once a virologic failure was documented, they could go on to other

therapies, and we've captured our endpoint and didn't really mess up the

trials. "

== end ODAC

And that (a reliable marker for a quality response) dear friends, was the

primary reason for the rapid progress against HIV … and the fact that agents

active against a virus are much easier to screen for compared to for cancers,

and also the high enrollment rates for trials in HIV (25% vs. 3% for cancer).

(NOT activist patient advocates, although they did drive important reforms in

the review process.)

So particularly in the indolent lymphomas we have an urgent need for a endpoint

that can be assessed in months rather than years .. the absence of minimal

residual disease (MRD negativity)

Finally to the article describing a technology that might bring us there.

=Nanotechnology Cancer Detection Technology Moves to Clinical Trial

The Gray Sheet. 2011 Mar 14, Z Miners

A first-in-man clinical trial to measure very small levels of residual leukemia

cells using a unique nanotechnology-based magnetic imaging method has enrolled

its first 35 patients.

The technology, in development by Senior Scientific and nanomedicine-focused

investment firm Manhattan Scientifics, is still years from reaching the market,

but the firms say they are in active partnering discussions with several large

drug, device and imaging companies.

The trial, which will enroll 60 patients in all, is expected to be completed

within two years. In leukemia, the focus is on monitoring the effect of

chemotherapy by detecting residual disease. The technique also has applications

in gauging therapy response in a range of other cancers, according to the

developers.

“If you’re doing chemotherapy, hyperthermia or even surgery, we can use our

device to see that you get it all,†said Flynn, founder and president

of Senior Scientific. “The leukemia case is just one example.â€

The companies are also assessing the tool for early detection of breast cancer,

other malignancies and Alzheimer's disease, he said.

Magnetically Measuring Cancer Cells

The technique being studied in the leukemia trial involves first extracting bone

marrow cells from leukemia patients; injecting the cell sample with magnetic

nanoparticles linked to antigens that preferentially bind to leukemia cells

rather than normal cells; and measuring the concentration of leukemia cells in

the sample by employing a patented magnetic biopsy needle and a specialized

sensor array for magnetic fields.

Flynn says the technology can detect " minimal residual disease " down to 0.3% of

a sample.

Details: http://bit.ly/gpNGAW

Karl

PAL www.lymphomation.org