t’s been said that geography is destiny. Should we accept this in medicine? Should the amazing advances in cancer therapy just be the sole property of those of us lucky enough to be born in wealthy countries? How do we get “precision medicine” to the millions worldwide who desperately need it?

Precision medicine is the merging of what we’ve learned from years of genetic discovery and functional biology with innovative drug design and manufacturing. The “poster child” of precision medicine is chronic myeloid leukemia (CML), where the unique BCR::ABL1 fusion gene drives the disease, and tyrosine kinase inhibitors (TKIs) directly block the pathogenetic pathway. As a result, patients receiving TKI therapy now live a normal lifespan. By way of comparison, when I came into this field more than three decades ago, the average lifespan of a patient diagnosed with CML was only seven years. That kind of progress sets a very high bar but does demonstrate the potential power of a precision medicine approach.

So, what you need is sophisticated molecular diagnostic testing, advanced drug development pipelines, and wham!, a near-magical result that is the model for all cancer therapy. Of course, this all means little to the vast majority of cancer patients who live in areas without access to the diagnostics or medicines that make this near miracle possible.

What Made This Possible?

For CML, creativity, cross-discipline partnerships, and plain hard work forged fantastic advances in patient care in low-resource areas. This success was fueled by a unique collaboration of a nonprofit (Max), “big pharma” (Novartis, then others), biotech (Cepheid), and academia (the Fred Hutchinson Cancer Center).

The Max Foundation. Established in 1997 in memory of a young CML patient, this group is dedicated to facilitating access to treatment for CML and other malignancies for the world’s most neglected populations. The Max Foundation entered into a partnership with Novartis in 2001 and now supports access to imatinib and five other TKIs for CML patients in 78 low- and middle-income countries. The organization has helped over 60,000 CML patients gain access to imatinib and now works with several drug and diagnostics companies to support access to multiple lines of therapy for CML and other cancers and rare diseases. Altogether, the Max Foundation has helped over 100,000 people in resource-challenged settings worldwide gain access to life-saving treatments.

Cepheid is a diagnostic company that makes a portable, affordable, cartridge-based, automated polymerase chain reaction (PCR) system that allows the rapid quantification of molecular targets with minimal technician hands-on time. Initially, Cepheid was interested in the detection of critical pathogens (for example, the Cepheid platform is used to test for anthrax contamination of the mail, sparked by the post-9/11 attacks on politicians and media). We helped Cepheid develop their quantitative reverse transcription–polymerase chain reaction (RT-PCR) assay for the BCR::ABL1 fusion gene. This was Cepheid’s first cancer test.

Dried blood spots (DBS). If clinics and hospitals do not have a local assay (Cepheid or otherwise), shipping of the sample by air to a referral lab is often the next-best option. However, this is expensive and not scalable. Shipping a single fresh blood sample from Africa to Seattle can cost >$500, and since samples must be sent fresh, batching is not possible. As a workaround, we developed an RNA-based assay for BCR::ABL1 using DBS. (The main hurdle in this work was finding the right paper that would limit RNA degradation but still allow nucleic acid extraction from the paper. This was not trivial.) Samples can now be batched and will yield accurate results even after weeks of travel. Thus, a clinic can send scores of samples for BCR::ABL1 testing even by regular post if economically necessary.

We have recently found that one DBS filter paper (which contains four spots) provides ample material for BCR::ABL1 testing, ABL1 mutation testing, and a full panel of myeloid mutation targets (using the Thermo Fisher Genexus platform). This thereby opens up a wide variety of applications, including blood-borne pathogen testing, mutation testing for other blood cancers, immunoassays (such as B and T cell repertoires), etc.

Less invasive sampling methods. Many clinics in low-resource regions have limited availability of needles and syringes. In addition, many patients must travel relatively long distances for visits, making disease monitoring all but impossible due to time and expense.

Can we develop a method to allow for simpler testing, even at patients’ homes?

Yes! We have worked with the bioengineering company Tasso (Seattle, WA) to test a device that adheres to the upper deltoid muscle and after activation inserts a needle, drawing blood onto a paper medium, creating a DBS from which testing can be performed (see above). We have found that this method yields quite comparable BCR::ABL1 results to normal venipuncture. Thus, community healthcare workers carrying devices and packs of filter paper can make testing available well beyond established medical centers.

So What? From Proof of Concept to Measurable Impact

This work demonstrates what is possible when access, diagnostics, and sustained partnership align:

1. More “curative” therapy to CML patients, everywhere. The remarkable partnership described above has delivered TKIs to tens of thousands of patients worldwide. The ultimate “so what” is the impact of this intervention on survival. So, take this as the ultimate “so what?” response: CML patients in this program have the same survival outcome as CML patients diagnosed and treated in wealthy, industrialized countries!
2. Facilitating treatment discontinuation. A large number of studies show that CML patients who have had a very deep molecular response that persists for years can discontinue their TKI therapy and remain without relapse (so-called treatment-free remission, or TFR) in roughly 50% of the time. TFR has advantages to the patient (improved quality of life from curbing drug-induced side effects) and to the medical system (costs). However, TKI discontinuation requires access to molecular testing so that if a patient does have a relapse, TKI therapy can be promptly reinstated. The Max Foundation supports over 13,000 patients worldwide who have taken imatinib for 10 years or longer, suggesting there is a large pool of people eligible for TKI treatment discontinuation. Indeed, the Max Foundation has recently shown that TKI discontinuation can safely be performed in the low- and middle-income country setting, with outcomes similar to those studies from academic centers in wealthy countries. This is a remarkable result.
3. Placing centralized genetic testing in low-resource areas, concentrating expertise and offering clinically significant testing and monitoring for an expanded set of cancers.
4. Allowing for sampling at a patient’s home, which is important not only in low-resource areas but also in rural areas in affluent countries, where patients must drive long hours to get to a lab. It’s easy to imagine a world where soon drones will be summoned by cell phone directly to the patient, where self-sampling can be performed, with the samples whisked back to a central lab for testing.

From Success to Scale: What It Will Take Next

To go to the next steps, we need:

• Dedication: We need more pharma and biotech companies to make the long-term investments in diagnostic and treatment access through organizations like Max that enable patients to support their families and contribute to their communities, strengthen local health systems, and create opportunities to build sustainable treatment for cancer that enables progress towards local self-sufficiency.
• Resources: We need governments across low- and middle-income countries to recognize the opportunity to improve cancer outcomes and invest what they can in the necessary resources to support the efforts of the nonprofit community with their partners to improve outcomes. Obviously, development and implementation needs creative financial solutions.
• Political commitment and prioritization from both providers and receivers. We will need dedication and a lot of patience, work, persistence, and drive.

We can do this. Let’s get to work. Patients and their families in underserved areas are wanting and waiting.