PATIENT SPOTLIGHT: Andrej Krivda, Wettingen, Switzerland
We interviewed fellow ALKie Andrej Krivda on his very interesting journey with ALK+ lung cancer and all the unexpected twists and turns he’s had to navigate since diagnosis. Andrej is the very first person to enter the Nuvalent NVL-655 clinical trial in Spain and one of the first patients to take part in the trial in all of Europe, and we were very interested in his perspective. He also happens to have a fascinating personal history. Enjoy the read!
Andrej wearing a T-shirt featuring his personal artwork
1) Tell us a little about yourself, your personal and professional background, and your journey with ALK-positive lung cancer so far.
I was born and grew up in Slovakia (what used to be Czechoslovakia) where I was educated and received a degree in Electrical Engineering in the transmission and distribution of electric power. Afterwards I moved to Delft in the Netherlands for further studies and got a PhD in high voltage Electrical Engineering. This explains my eagerness to try out the Novocure electrodes which apply high frequency electric fields (Tumor Treating Fields) across a tumor and gradually eradicate it. I spent my post-doctoral years in Stockholm, Sweden, and Brisbane, Australia. I've lived in Switzerland since 2001, where I worked on high voltage electrical insulation - high voltage cables, transformers, outdoor insulators. In my free time I played chess, painted and exhibited my paintings in small galleries, and listened to music - anything from jazz to classical.
I was diagnosed in May 2019 when I was 52 years old. I used to have high blood pressure and was taking Amlodipine, but I developed a dry cough. This is a listed side effect of Amlodipine. So, I changed to Ramipril, but I still suffered from dry cough (also a listed side effect), so I decided to stop taking Ramipril and do more sports and eat healthy. I have never smoked, and I have not drunk alcohol on a regular basis, so I thought I would manage. But my cough had not gone away even a month after I stopped taking Ramipril. I thought it was odd. And then one day I saw three tiny (1 to 2mm) red traces in my saliva - I thought "These must be tomato pieces I just ate". Two weeks later I saw red traces in my saliva again, but I had not eaten tomatoes. So, I decided to go to my general practitioner, and I was thinking that perhaps I had tuberculosis, although I had not visited any exotic places. So, the doctor performed a lung function test, then an X-ray, and then he sent me to Computer Tomography. The radiologist saw a shade in my left lung, and I was immediately referred to a pulmonologist at the University Hospital in Zurich. There I was sent for a PET CT scan, and that is how everything started. The pulmonologist sent me to an oncologist at the same hospital where they took my blood, and I waited for two weeks for the results. When I went back to the hospital, my oncologist arrived and told me with a big smile on her face "You have an ALK mutation!!" and I thought "???****". Now I understand why [she smiled], but at that time I did not know anything about lung cancer.
I started taking Alectinib within a week. And I suffered from horrible constipation. I started eating more vegetables and fibers, and the situation gradually improved, but it never returned to normal. I spent the first six months at home at 100% salary - this is what my health insurance allowed in Switzerland, but then I was basically kicked back to work where I worked two days a week, but it seemed like the full 5 days a week! I think that work stress contributed to my progression twice, the first time while on Alectinib and later while on Lorlatinib, so my advice would be to avoid stress ... I was taking Alectinib for 18 months and then I progressed rather aggressively. My oncologist unfortunately did not pay attention to my symptoms and did not move up my scheduled CT scan. If she had done this, I would have avoided a month in the hospital hanging between life and death. My legs were swollen as big as tree trunks; I could sleep while sitting, and according to her that was "normal". And so, I progressed on Alectinib with a pulmonary embolism, 1.5 liters of water in my lungs and a bleeding tumor in my left lung. It was very bad; I had shallow and fast breathing, but luckily, we live only 10 minutes' drive to the local hospital in Luzern. Since I had a pulmonary embolism and a bleeding tumor at the same time, estimating the correct dose of blood thinner was tricky, but I’m still here to tell the tale. The most amusing fact for me was that all this happened one day before the scheduled CT in Zurich. The Swiss protocol does not allow taking Lorlatinib before a minimum of two other inhibitors are given to a patient. So, we tried Ceritinib, which both I and my oncologist knew would not work. That was for about one week, when the CT was repeated, and I had to wait for liquid biopsy results for almost three weeks. In the meantime, they cauterized veins leading to the tumor in the left lung to stop it from growing and to stop bleeding and installed a filter into my artery to stop any large circulating blood clots from clogging the veins in my body. And I was moved from Luzern to University Hospital in Basel to have a lung valve installed, so that blood from the bleeding lung tumor did not go to certain parts of the lung, and then back to Luzern because of the health policies of various regions in Switzerland. After Ceritinib I was given one round of chemo (Cisplatin+Pemetrexed), and I ended up hiccupping for five days non-stop.
Finally, the results of the liquid biopsy arrived and showed that I had the ALK G1202 mutation, and I was allowed to take Lorlatinib. The pain disappeared within one hour!!! I was astonished. After three weeks in the hospital spent mostly lying in bed, I lost almost 25 kg (I went from about 92kg to about 67 kg). So, I came home, and a very slow recovery process started. My wife walked with me for 10 meters outside of the house (the road was icy and rather slippery) and back - that was my first walk outside! Every day I tried to push the limit by 2 to 3 more meters... It was very frustrating to see eighty-year-old pensioners with a walking stick zip by next to me with incredible speed. It took me nine long months to slowly recover. I went back to work two afternoons per week, but it felt like the full week, and after two months of work I progressed again, and a liquid biopsy in January 2022 showed a double mutation G1202/G1269. Having no other options, I started chemotherapy, Carboplatin+Pemetrexed, but after five rounds my creatinine values jumped to 200 (the limit is below 110) and my eGFR kidney filtration rate to 30% (healthy persons have eGFR>90%). In the meantime, I was trying to apply for the dendritic cell ALK vaccine trial in Lausanne, Switzerland, but they needed fresh tissue which I did not have. They did not find any tumor tissue even when they removed the lung valve in Basel. The lung valve was causing infection in my lungs which resulted in spitting mouthfuls of blood if I irritated the place where it was installed by, for example, vacuum cleaning or biking on a bumpy road ... I asked my oncologist to apply for the Novocure electrodes which I started wearing in May 2022. Novocure has two European centers, one in Germany and one in Switzerland, and they also performed one of their trials for brain and lung cancer almost a decade ago in Switzerland with huge success.
Despite all my efforts, I progressed again in October 2022 when the liquid biopsy confirmed the double mutation from January 2022. I already knew about the Nuvalent 655 trials in the US and their openings in Europe in Paris, France, and Barcelona, Spain, and my oncologist applied for these trials and told me that Paris was full with a long waiting list, but that Barcelona was open, their only condition being that I had to stay there for the first two months nonstop due to all the testing. And so, I became their first Nuvalent patient, perhaps even the first in Europe! Once I arrived in Barcelona, qualifying tests started. The major issue was my creatinine values which were about 200 and eGFR around 40%. But by taking the powerful antioxidant acetylcistein, which protects kidneys against damage, and omega 3 and coenzyme Q10 supplements and going on an all-plant diet with no meat, I managed to lower it below 170. They also thoroughly check your eyes as some other inhibitors have caused vision problems in the past. And then the most important period started - I had to stop taking Lorlatinib for 7 days. The first three days were OK, because Lorlatinib was still in my body, but the last four days were very difficult since my body had no protection against cancer which was growing insanely fast. I could barely walk, and I was coughing every five meters. Walking up the stairs or uphill, even on a gentle slope, was practically impossible. But then I started with the first pill and spent 12 hours in the hospital for observation. In the morning there was a meeting with my oncologist, and in the afternoon I was given the first pill. Within two hours I felt an enormous surge in energy and my coughing decreased by 50-60%. Since this is a new experimental medication, for which Nuvalent has to find the correct dose, we started with 25 mg per day. Nuvalent so far has not disclosed the exact molecular weight or bioavailability of their new medication, so it is not possible to calculate how many molecules of Nuvalent 655 are needed per human cell. But even 25 mg work quite well for me since my tumors decreased by 50% within the first six weeks of treatment. I think I must thank the superb molecular design of Nuvalent 655, since the medication was designed to treat the G1202/G1269 compound mutation. I also consider Nuvalent 655 the best inhibitor ever because it avoids various neurological problems which plagued other experimental inhibitors. This is achieved by avoiding TRK pockets and selecting only ATP pockets in ALK despite being 70% similar to others - only superior molecular design allows this. I just hope that there will be no long-term side-effects which would stop the treatment with Nuvalent 655 and that in the meantime a CURE will be developed for this nasty disease!!!
2) What do you know now that you wish you knew back when you were first diagnosed? What would you advise a newly diagnosed patient?
Learn as much as possible about your disease because your conventional oncologist may not know everything. Sometimes they simply do not care as much as they should, and you should inform your oncologist on the latest developments. If they do not listen to you, then it is time to change oncologists. Try to read professional papers on ALK lung cancer even if you understand very little. When you read the next paper, you will already understand a bit more, and gradually you will become more educated about your disease. It takes a lot of energy and effort, but in my opinion it is worth it.
Always look for new treatments in case your cancer progresses, because then you are at least mentally prepared, and you can act fast or push your oncologist to act fast. Unfortunately, ALK lung cancer can spread very rapidly, and it is not localized like some cancers which can grow in one location over a long period of time, and you also must act fast without delay.
Having a clean PET CT scan does not mean much since the resolution of the standard PET CT scan is 3 mm x 3 mm x 3 mm, and anything smaller is not visible to the scanner, and even a small, say 1mm in diameter, tumor can easily contain hundreds of millions of cancer cells. In addition to the PET CT scan, I like to add the CEA tumor marker value, and if I see that it is below the limit or it has a decreasing trend based on monthly observations, then I am satisfied. I had several scans which showed negative results over a period of 7-8 months, but my tumor marker was increasing up to 200 (the limit is 5 and at the diagnosis my CEA was around 600) - and the scan was still negative! I knew that something was going on despite having a clean scan.
It would be great to have one-or-two-page-long ALK lung cancer manual with advice for new patients - a quick summary of best practices by leading oncologists. For example, get a liquid/tissue biopsy when you are progressing. When you are progressing and ALK does not show any new mutations, check for MET amplification using the FISH test; what to do when you are progressing on Alectinib, and what to do when you are progressing on Lorlatinib, and so on.
3) You are one of the very first Europeans to take part in the Nuvalent clinical trial. How has your experience and results been so far? Any challenges with logistics or side effects? Anything else important the ALK community should know about the trial?
I have already mentioned the Nuvalent trial above. I just want to add that Hospital Vall d'Hebron in Barcelona, Spain, has huge experience in conducting various Phase 1 trials. For example, at the hospital I met another ALK group member who has been participating in a Phase 1 Lorlatinib trial since 2018 and Lorlatinib has been working for her for the last five years! This kind of news can really give hope to other patients.
The team at Vall d'Hebron is very professional and friendly, and it has nothing to do with me bringing them 3 kg of the finest Swiss chocolate for their work :-). Testing during the first two months was quite intensive. I had to go to the hospital two to three times per week, and sometimes I spent 10 hours at the hospital. I was living in Barcelona with my brother's father-in-law.
I would like to emphasize that ALK patients have to be aware of potential kidney damage by chemotherapy which can disqualify them from clinical trials. Some patients can take twenty rounds of chemotherapy without too many problems, while I managed only five rounds. So, watch out for those creatinine and eGFR values for kidneys when you are on chemotherapy.
4) You are always on the lookout for new research, new therapies, new products that can help with this disease, and you always actively update the members of our Support Group on your findings. Other than the Nuvalent trial, are there any other therapies, trials, or research that makes you excited? Anything you currently have your eyes on?
Cancer research is very dynamic, and the areas where I would invest my money today would change as new ways of combating cancer are developed. In general, I am looking for a CURE, as inhibitors do not work for everyone, and they may have unpredictable side effects. I am a great fan of immunotherapy, in which your own body fights cancer cells, and if I had 100 million dollars, I would invest 60 million into development of an ALK vaccine, as I consider this to be a potential cure, especially a vaccine for which you do not need tissue sample, because it may not be available in many cases. The remaining 40 million I would probably invest in various projects related to the basic science of understanding ALK cancer. We still do not know why one patient develops the G1202R mutation and the other, say, the L1196M mutation, or why one suffers from sensitive skin while the other suffers from swollen legs. Just by following various ALKtALKs, one can see that there are many ideas to follow, but we would have to try them out one-by-one. For example, I was quite fascinated by the idea of preventing formation of ALK fusion protein pairs, as these signal cell centers to multiply. Would it work? I do not know, but we would need human and financial resources to find it out. Also, Lorlatinib analogues, which are molecules very similar to Lorlatinib but much more efficient than Lorlatinib for certain ALK mutations, would be worth pursuing further.
We do not know what new technologies, which would allow us to find new ways to treat cancer, will be available in future. For example, two hundred years ago people did not have any idea about computers, DNA, electron microscopy etc., and thus they were not even able to generate ideas to treat cancer.
I would also like to make several points which I consider quite important.
First of all, I wish that every ALK patient would have such strong support from their partners, family and friends as I have.
Implementation of new cancer medications is too slow for many cancer patients, and we need to find ways to accelerate this process.
The cost of cancer medication is insane, and I see waiting rooms full of cancer patients. This is not sustainable, as neither governments nor health insurance companies can afford it in the long term. Lorlatinib was only introduced in Denmark in 2022 and in Switzerland in 2019 due to cost, and Lorlatinib is still not fully approved in Canada. In the meantime, patients are dying. It is sad to realize that your government does not care about you only because you stop paying taxes when you are ill, and you are too expensive to be treated. Even in Switzerland, while I was dying on a hospital bed in 2021, there was a protocol which did not allow me to take Lorlatinib before two other inhibitors had been tried out. Such restrictive protocols must be changed for critically ill patients, as disease can progress very fast, and there is no time to “dilly-dally” with another inhibitor when a patient is dying. And unless you have cancer, you rarely understand what it means to have it.
Also, I hope that one day the world will unite and start spending money on issues which really matter for humanity and not waste precious resources on senseless wars. The present war in Ukraine is already costing taxpayers of many countries several trillions of dollars. Imagine if this money was spent on cancer research!!!
We should convince very rich people to invest more into cancer research. At the present time they rarely do so, and if the disease affects them personally, then it is too late for them. What would happen if we could convince Elon Musk to spend some of his billions on curing ALK lung cancer?
Interview by: Christina Weber