Oncology and hematooncology - from precise diagnostics to innovative therapies

As noted by Krzysztof Jakubiak, who led the discussion, we spend about 60 million zlotys annually on molecular diagnostics, which is half a percent of all spending on cancer treatment. Meanwhile, a significant portion of new therapies that are covered by reimbursement are only available to patients with specific mutations confirmed by molecular tests - no diagnostics, no modern treatment. - Won't diagnostics block the inclusion of patients in treatment programs, he asked.

Andrzej Tysarowski, M.D., head of the Department of Genetic and Molecular Diagnostics of Tumors at the National Cancer Institute in Warsaw, coordinator of genetic diagnostic guidelines under the National Cancer Strategy, reminded that molecular diagnostics not only allows a patient to qualify for a drug program targeted for a specific mutation, but above all enables the proper diagnosis of cancer. - Today, microscopic testing is not enough," he said. But that's not all - thanks to molecular testing, it is also possible to monitor the progress of treatment, to see how the profile of a cancer cell changes. Last but not least, molecular testing also has preventive significance - when there is a genetic risk associated with cancer.

Molecular diagnostics has more than one name, as it consists of simple tests of a specific gene, complex tests involving several, a dozen or more genes, and tests of several hundred genes or even the entire genome. - We have the technology, equipment, capabilities. The quality and class of research performed in Poland is absolutely comparable with Western European countries or the US. What differentiates us is funding," Dr. Tysarowski pointed out. At the moment, the public payer finances basic gene tests and simple panels - primarily in breast, ovarian, colorectal, pancreatic or melanoma cancers. - We lack funding for advanced testing, which is necessary in some cancers," he stressed. Tests covering 6,000-8,000 genes are not reimbursed, although in sarcomas or certain ovarian and lung cancers, for example, they would make a difference to the patient. - We have the technical capacity to perform these tests, and efforts are underway to include them in funding for adults. The population up to the age of 18 already has guarantees of funding from the Medical Fund," he stressed.

A breakthrough in access to diagnostics would also be to provide funding for liquid biopsy, a test performed from the peripheral blood, which makes it possible to obtain the gene profile of a cancer cell without the need to collect material for testing. - Sometimes a simple biopsy is either impossible or very invasive for the patient, the expert recalled.

Prof. Iwona Hus, president of the Polish Society of Hematologists and Transfusiologists and head of the Hematology Department at the National Medical Institute of the Ministry of Internal Affairs and Administration, stressed that also in the field of hematology, an essential standard for patient diagnosis and treatment is the use of molecular tests. - Proper care is basically impossible without such tests," she said, while adding that it is hard not to notice the progress that has been made in recent years. - Not long ago, during such discussions, we argued for the need to provide or expand reimbursement for innovative therapies.

Because in hematooncological diseases - both chronic and acute myeloid leukemia - the traditional treatments available to date are being supplanted by targeted therapies, but the prerequisite for their use is, of course, the result of a molecular test. - We can use such therapy for acute myeloid leukemia already in the first line of treatment, provided that the gene mutation is determined. The sooner we perform such a test, the sooner the patient will receive treatment," she stressed. Also in the case of lymphomas, Prof. Hus explained, classification is increasingly based on molecular testing, which also determines treatment.

The expert stressed that molecular testing is important not only because it opens the path to treatment for patients (or protects them from the use of ineffective and debilitating therapies). - Thanks to molecular testing, it is also possible to monitor treatment, to determine residual disease, she enumerated. At the same time, she pointed out that even if the payer already finances the necessary tests, as in the case of chronic lymphocytic leukemia, they are reimbursed under the drug program. - However, they must be performed before a patient qualifies for the program. And what happens if the patient cannot qualify?

Continuing on the topic of hematooncological diseases, Prof. Krzysztof Giannopoulos, head of the Department of Experimental Hematooncology at the Medical University of Lublin, pointed out that the results of genetic testing make it possible to make a diagnosis, but also to determine the prognosis. - Plasmocytic myeloma or leukemia is no longer a single disease. There are dozens, even hundreds of them. We have more than a hundred types of lymphomas alone, which differ primarily in genetic characteristics.

The expert explained that for plasmocytic myeloma (or rather - plasmocytic myelomas) there is no targeted therapy. - We have two risk groups, high-risk and standard-risk, and our drug program offers effective treatment to patients who have a worse prognosis because they are at high cytogenetic risk, although standard-risk patients respond to this treatment just as well or even better, he explained. In addition, he said, the drug program - specifically the inclusion criteria - has not kept pace with the update of the risk index, in which significant changes have been made in recent months. Hematooncologists would expect to see changes in the reimbursement rules that would either take into account the expansion of the drug's indications to include patients who meet the unrecognized criteria, or even abolish the inclusion criteria, offering effective, life-prolonging treatment to all patients with plasmocytic myeloma, regardless of which risk group they are in.

As Prof. Giannopoulos stressed, the response of patients to this treatment varies, sometimes even following a relapse. This is also why, he said, the treatment of a patient with a high cytogenetic risk needs to be planned much more precisely, choosing optimal options. - If a patient is qualified for transplantation, it is best to perform a tandem transplant six months apart, he recommended. Maintenance treatment also plays an important role, which Polish researchers have shown to be effective in the ATLAS trial. - The three-drug regimen is proving more beneficial for patients than the single-drug regimen, the expert said. As he reminded, the current standard for maintenance treatment after bone marrow transplantation is the administration of lenalidomide, while the ATLAS study showed that the KRd three-drug regimen, in which carfilzomib and dexamethasone are used in addition to lenalidomide, is more effective. - We are currently waiting for reimbursement decisions. Reimbursement was requested by the medical society through the national consultant, because the study was non-commercial, he recalled.

A powerful problem in Polish oncology, as discussed by Aleksandra Wilk, director of the Lung Cancer Section, TO SIĘ LECZY Foundation, is prevention. According to the latest data, already from the post-pandemic period, only 13 percent of lung cancer patients reach doctors at a stage where they can be operated on. They are the ones who stand the best chance of reaping the benefits of innovative therapies that can be incorporated after surgery, although life extension opportunities are also emerging for patients in more advanced stages of lung cancer. - Modern therapies are changing the face of lung cancer treatment, Aleksandra Wilk stressed. Medicine is offering patients much more than chemotherapy, which, the expert admitted, "didn't extend life very much." At the moment there are targeted therapies, which of course require advanced molecular diagnostics. There is immunotherapy, included after chemotherapy, which reduces the risk of relapse by more than half. Based on the results of the study, 250-300 patients could currently benefit from such innovative treatment, although, Aleksandra Wilk said, if there were a breakthrough in prevention and patients were brought to doctors early enough, this number would certainly increase significantly.

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When we say "prevention" we think "education" and - at the same time - "awareness". - An aware patient will not agree to the automatic application of current treatment regimens, he will inquire about the possibility of innovative treatment, to perform more advanced diagnostics," admitted the representative of the foundation. The problem is that this awareness of the patient is built - very often - already at the stage of diagnosing the disease, while before that there is a lack of (usually) education resulting in a more regular control of one's condition.

It is certainly worth posing the question of whether and to what extent patients - especially those diagnosed with cancer - have an idea of the possibilities of modern diagnostics and treatment. But knowledge is one thing, and needs are another. - Patients, especially those with rare mutations, need comprehensive molecular testing. There are drugs for them, but they need to be accurately diagnosed in order to benefit from them," recalled Aleksandra Wilk.

Mateusz Oczkowski, head of the Reimbursement Department of the Department of Drug Policy and Pharmacy at the Ministry of Health, when asked if the department has data on what proportion of innovative therapies approved in previous years - and currently approved for reimbursement - requires the use of precise diagnostics, said that no analyses had been conducted in this regard, although he stipulated that they would be prepared if necessary. The answer would be, as Krzysztof Jakubiak, who moderated the discussion, explained, to the extent that reimbursement decisions seem to be ahead of solutions allowing access to diagnostics, without which there is, as experts stressed, no real availability of drugs. The health ministry representative agreed that just as for many years there were the biggest delays in reimbursement issues, in recent years the "reimbursement express" has overtaken everyone: not only in diagnostics, but also in the very contracting of drug programs there are delays. - The Ministry is setting the pace," he stressed, adding that this can't be stopped, which is why the new reimbursement lists will again include novelties. - In 2022, we have reimbursed 115 new molecular indications, forty of them in oncology, he recalled. In the first six months of this year, the ministry decided on 58 new molecular indications (39 in oncology). - There will also be a lot going on in July," Oczkowski stressed, signaling that not all demands will be met in the summer. - As for new options in lung cancer, perhaps a decision will be made in September, he said.

Tomasz Latos, chairman of the Parliamentary Health Committee, also said that changes in diagnostics must accelerate. - In terms of the organization of oncology treatment, we are dealing with almost tectonic changes after the introduction of the National Oncology Network. The changes in diagnostics are not so visible," he admitted. As he said, since in just over seven years "we have practically more than doubled health expenditures," expectations are enormous. - One would like spectacular solutions, he stated. And such achievements, he stressed, are occurring in reimbursement. - This used to not be the case. They were even looking for arguments not to reimburse medicines," he referred to his long parliamentary career. As he said, patients and patient organizations see these changes and appreciate them.

As he stated, "one always wants more." However, this "more" will have to be realized in the next term, in which the challenge is expected to be to make valuations of medical procedures more realistic and (further) rationalize spending in health care. The head of the Health Committee admitted that there is much to be done in the area of diagnostics, but it is necessary to approach the problem systemically. - At the moment we are spending hundreds of millions of zlotys on state-of-the-art equipment for diagnostic imaging. But realistically, there is beginning to be a shortage of specialists to describe examinations, and as a result, patients are waiting longer for the result of the examination than for the examination itself," Latos admitted. In his opinion, it is also impossible to avoid discussing the overuse of examinations, when it is known that in up to one-fifth of cases the standards of diagnostic procedure are not followed - for example, because a CT scan is performed instead of an MRI. - The question arises about the possibility of even inducing new cancers through excessive use of the test using ionizing radiation, he reminded.

Although the MP praised the Health Ministry for its progress, it was not without a spoonful of tar. This is because he admitted that not all decisions are being made as quickly as they should and could, in his opinion. He pointed to the lung cancer screening program, which uses low-dose CT, as an example. The pilot program is about to end, and there is still no decision on placing such a test in the basket of guaranteed benefits. - We have discussed this many times, but decisions are made in other bodies," he recalled.

Prof. Anna Latos-Bieleńska, chairwoman of the Council on Rare Diseases and national consultant in clinical genetics, also stressed the importance of systemic changes. - There will be no improvement in the area of genetic diagnosis if we do not have a law on genetic testing, she said. In her view, although there has been talk of the need for such legislation for years, it is only advances in the field of genetic testing that have changed the urgency status of the issue, so to speak. - Until recently, there was no high-throughput genomic testing, the results of which give access to huge amounts of data. This information must be protected. Genomic testing is done for strict medical indications, she stressed, but it has also become a "fashion" for such tests, and some laboratories are adapting their offerings to market demand. - The patient does not know which laboratory to use, which tests to perform. This is a breeding ground for swindlers," she concluded, adding that this is not just a Polish problem, because all over the world legislation is lagging behind the development of genetics.

This, however, does not change the fact that we need to hurry with the passage of the law, if only because without it there is no way to certify laboratories. As the expert said, the demand for genetic testing is growing by leaps and bounds. On the one hand, their development is envisaged by the National Cancer Strategy, on the other hand, all the time, she said, patients are waiting for the availability of these tests in the area of rare diseases. An opportunity for a breakthrough is the implementation of the National Plan for Rare Diseases. The problem is that patients are waiting, but they can't wait. Prof. Bieleñska-Latos admitted that we should already be performing four, maybe even five times as many tests - and in oncology alone. Speaking about the potential of genetic diagnostics, she said bitterly that what saves the situation is the fact that tests are not being performed, or rather, very few are being performed. - Otherwise, I don't know how long we would be waiting for a result.

The problem, of course, is personnel. A certain lifeline turned out to be the Law on Laboratory Medicine, because there it introduced a catalog of majors (including biology, biochemistry), the completion of which allows one to start specializing in medical molecular genetics.

Needless to say, without a quality law, it is difficult to ensure, the expert said, the proper quality of genetic testing. - The requirements for personnel, equipment, which laboratories will have to demonstrate, must be written there, she stressed. However, the environment is not waiting with folded hands for the law - voluntary certification of laboratories is already underway, the process is likely to be completed in September. - I will strive to ensure that only certified laboratories will be able to perform genetic tests, financed with public funds," Prof. Bieleñska-Latos said.

Quality and availability. Prof. Krzysztof Giannopoulos pointed out that contrary to popular judgment, the availability of patients for genetic diagnostics is not geographically determined. - If a doctor is aware that a test is needed, feasible and funded, he or she has no problem outsourcing such a test. I know small centers that provide much better diagnostics than huge hospitals," he stressed.

He also reminded that in order to maintain high quality, certificates cannot be given to laboratories "once and for all," that they must even constantly - regardless of whether they win national or European certificates - undergo evaluation. The condition for the quality (but also indirectly and availability) of diagnostic tests is, in the expert's opinion, the knowledge of both doctors and diagnosticians, but also their exemplary cooperation. Only then are reliable results obtained, which are the basis, he reminded, for optimal therapeutic decisions for patients.