In the U.S. and other high-income countries, access to testing and first-, second-, and third-generation tyrosine kinase inhibitors has improved the management and prognosis of patients with chronic myeloid leukemia (CML). Those improvements have not trickled down to the vast number of patients with CML living in low- and middle-income countries, where access to these resources is limited. As part of this year’s ASH Education Program, experts will describe the obstacles to providing these services, as well as international partnerships to overcome them. Here, session chair Hemant Malhotra, MD, and speaker Jerald Radich, MD, preview the discussion.
What are the greatest challenges to providing chronic myeloid leukemia (CML) testing and treatment in resource-poor areas?
Dr. Malhotra: There are several challenges where I practice in India, and also other low- and middle-income countries. First, the average patient travels about 250 kilometers for his or her cancer care. So, it is difficult for a patient with CML to come for frequent blood tests and monitoring. Holidays, festivals, family events, weddings, and other barriers to travel might also preclude a patient from reporting to the clinic on schedule.
The second hindrance is the cost of the tests. BCR-ABL monitoring in India costs about 6,000 rupees, or $100. In the U.S., that may not seem like much; for a country with an average monthly income of about $150 per family, paying for that test is a big issue.
Third, testing labs are few and far between. Few private labs monitor BCR-ABL using the international scale. Quality control in a private lab also is difficult for a treating physician to trust.
Dr. Radich: There are many obstacles that Pat Garcia-Gonzalez, cofounder and CEO of the Max Foundation, a nonprofit organization that donates oncology products to underserved populations, will address in her presentation. The foundation has developed relationships with pharmaceutical companies to offer CML treatment to patients in lower- and middle-income countries free of charge for life, which is rather remarkable. But first, it needs to identify patients with CML. I’ve been working with the Max Foundation for almost two decades to develop low-cost methods for diagnosing CML in these areas and eventually get patients on the path to treatment. Despite the successes we’ve seen, it still can be difficult just to provide the drug to patients in their countries. Some countries want to tax the drug, even though it’s free, so unfortunately, we can’t get to patients everywhere.
It’s a Herculean effort, and the fact that the foundation has been able to pull it off with more than 60,000 patients – who now have the same life expectancy as patients with CML in North America – is remarkable. Frankly, it’s kind of a miracle.
Can you tell us about the Spot On CML project? How is it helping to improve prognosis for patients in limited-resource areas?
Dr. Radich: The Spot On CML project is a partnership between our lab at Fred Hutchinson Cancer Research Center, the Max Foundation, the International Chronic Myeloid Leukemia Foundation (iCMLf), and the biotech company Cepheid. We developed a paper-based test where physicians in resource-limited areas could apply a spot of a patient’s blood to special paper card, then send the card to our lab via snail mail for processing. The previous method – sending vials of blood to labs in Europe or the U.S. for testing – was prohibitively expensive and risked damaging vials in transit. During the first year of using this paper-based method, roughly 500 patients were diagnosed with CML.
Without access to newer treatments or diagnostic testing, how are patients treated? How do local clinicians adapt?
Dr. Malhotra: In India, we have several generic versions of imatinib, one of the tyrosine kinase inhibitors (TKIs) used for frontline treatment. In some institutions and some countries, patients can access the drug without cost because it is available through the government hospital essential drug list. But that applies only to the first-generation TKI. For the patient with CML who has a heavy tumor burden or high-risk disease at diagnosis, we don’t have the option of offering them a second-generation TKI upfront, primarily because of cost.
In my hospital, I start all patients on imatinib and increase the dose if a patient has higher-risk CML. Imatinib works for about 70% of patients. If it doesn’t, we try to arrange access to a second-generation TKI, but this can be a difficult exercise. We try to counsel patients for the first year after their diagnosis to test for BCR/ABL every three months, but after the first year, we test most patients every six months, and sometimes annually. Still, some patients find even that stressful. And, even if the patient has frank resistance to firstline imatinib, we often are not able to run a kinase-domain mutational analysis, because it is available only at a few major centers and some private labs and is unaffordable for many patients.
So, primarily because of patient logistics and costs, we often are not following the standard guidelines for managing CML, such as testing every three months.
Are there efforts to build capacity or provide training for clinicians in these areas?
Dr. Malhotra: I would answer that with an unequivocal yes. Since we have 1.4 billion people in India, we have so many patients living with CML. We are expecting to see about 150,000 patients with CML in the next five years, primarily because patients are living with the disease longer thanks to the excellent treatment options we have.
However, there are too few hematologists and oncologists to care for this large volume of patients. Research groups, such as the Indian CML Study Group, are now going to medical college hospitals, talking to physicians, and providing continuing medical education programs, conferences, or one- or two-hour meetings about diagnosing, monitoring, and managing the disease to help educate the clinicians who will ultimately take care of the CML patients in their local areas.
How important are the international collaborations between medical centers, or the involvement of nonprofit organizations?
Dr. Malhotra: Collaborations are crucial to treating this disease in areas with limited resources, especially collaborations among physicians. I am one of the advisers of the iCMLf, which has an incredible website where clinicians can post challenging cases in a “Clinical Case Discussion Forum” and expect a response within 24 hours from world leaders in the field.
The iCMLf also runs a clinical preceptorship program, in which 20 selected hematologists from lower- and middle-income countries complete a three- to four-week preceptorship at a global CML center of excellence in Europe, the U.S., or Australia. Participants learn about the latest treatment options, laboratory aspects of testing and monitoring, and how to adapt those to the resources available at their home institution. It’s an incredible program.
Dr. Radich: The value of partnerships like Spot On CML is beyond measure. There are so many different moving parts that require so many people working together – from the people on the ground who find patients, to the shipping companies and drug companies willing to sacrifice profits to help us out, to the patients and doctors themselves.