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from the moment he received the admission letter, yuhao (pseudonym) began to look forward to his university life.

yuhao is 19 years old this year. he has a buzz cut and is full of youthful vigor. he likes to stay at home and play games, but he also likes running, walking, and riding bicycles with friends at night. this year, he was admitted to nanjing university of posts and telecommunications, a double first-class university, with a score of more than 600. tomorrow (september 7) is the official start of school. as a new college student, he is full of expectations for the upcoming four years of college life.

it is hard to tell that this teenager is a cancer patient. just before the start of school, he had just finished his fourth chemotherapy cycle.

i thought it was just tonsillitis.

around the qingming festival this year, yuhao felt some changes in his body. he always had a headache after waking up every day, accompanied by difficulty breathing and swollen tonsils. after a check-up at a local hospital, he thought it was a simple tonsillitis and was given intravenous drips in the hospital for a week, but the effect was minimal.

after evening self-study, he always ran one or two laps in the school playground, but even after the "treatment", he still often "got tired after walking a few steps" and had a headache so severe that he couldn't attend class. it wasn't until early may that his parents realized the seriousness of the situation and took him to the hospital for a pathological biopsy. "at the time, they suspected it was lymphoma, so they asked us to go to a tertiary hospital for confirmation."

yuhao's parents panicked and immediately took the pathology slides to the zhongda hospital affiliated to southeast university in nanjing. a week later, yuhao was diagnosed with diffuse large b-cell lymphoma (dlbcl), a highly invasive and rapidly developing blood system malignancy.

lymphoma is one of the most common malignant tumors in china and one of the few malignant tumors that can be cured. according to the pathological characteristics of tumor cells, lymphoma is mainly divided into hodgkin lymphoma (hl) and non-hodgkin lymphoma (nhl), of which nhl accounts for about 90% of all lymphomas.¹the most common type of nhl is dlbcl, which yuhao suffers from, accounting for about 35%-50%²。

dlbcl is similar to other subtypes of lymphoma in that it can originate in any organ or tissue of the body. symptoms include systemic symptoms such as unexplained fever, night sweats, weight loss, skin itching and fatigue, as well as local symptoms such as dyspnea and sputum in the lungs. the most common manifestation is painless progressive lymphadenopathy. therefore, in most cases, the disease is hidden and difficult for patients to detect.

"yuhao actually had symptoms because the mass grew in his nasal cavity, causing nasal congestion and then headaches," said zhang xiaoping, yuhao's attending physician and deputy chief physician of the zhongda hospital affiliated to southeast university. he added that because he sought medical treatment relatively promptly, yuhao's condition was classified as stage ii according to the ann arbor staging system, involving the nasal cavity and one lymph node area. "it is not serious and the prognosis is good."

zhang xiaoping. photo provided by the interviewee

on the other hand, dlbcl is also relatively difficult to treat among all lymphomas. zhang xiaoping explained that the difficulty in treatment lies in its recurrence and refractory nature. according to the data, the 5-year overall survival rate of dlbcl patients is about 60%-70%, which is not low. more than half of the patients can achieve and maintain complete remission after first-line treatment.ease³(the tumor disappears completely and lasts for at least one month.) however, the remaining 30%-40% of patients usually relapse within 2 years after the first-line treatment.⁴。

“once it relapses, it is very difficult to treat."zhang xiaoping said that although there are second-line and later-line treatment options for relapsed/refractory dlbcl, the overall survival rate of patients is not high, and such patients often have a worse prognosis and a shorter survival period.therefore, when seeing patients with dlbcl who are being treated for the first time, doctors hope to give them a better first-line treatment plan. as long as there is no relapse within two years, the chance of relapse will drop significantly, and if there is no relapse for five years, "then the disease is basically cured.”

before 2023, the standard treatment for first-line dlbcl worldwide was the r-chop regimen, which is a targeted drug rituximab (r) combined with four chemotherapy drugs (chop, each letter represents a chemotherapy drug). "the r-chop regimen has been in power for more than 20 years. the medical community has actually been making various attempts, such as increasing the intensity of chemotherapy, and adding another chemotherapy drug to form the r-chop+x regimen, but none of them have further improved the first-line efficacy." zhang xiaoping said that until january 2023, vepotuzumab (pola) was approved for marketing in china, with the indication of first-line treatment of dlbcl in combination with r-chp, giving patients a higher chance of cure.

a breakthrough in first-line treatment

yuhao was the first to try the new first-line treatment option of pola-r-chp.

because they didn't want to put too much psychological pressure on yuhao, his parents didn't tell him the details of his illness in time, but just explained that it was a little inflammatory and he needed to hang intravenous drip for a day to reduce inflammation. yuhao himself also took the college entrance examination very seriously. this was the time to reap the rewards after years of hard work, and an ideal result would be worthy of the years of hard work.

there were still more than 20 days before the college entrance examination. dlbcl is a highly invasive disease. if it is not controlled in time, the growth of the tumor in his body may be further accelerated, and the consequences will be even more disastrous. after discussing with dr. zhang xiaoping, his parents decided to use a one-day dose first. "use the best, no matter what the cost, as long as the effect is good," said yuhao's mother.

the treatment recommended by zhang xiaoping is the vepotuzumab regimen. she explained that the reason for choosing this regimen is that haoyu is relatively young and will soon take the college entrance examination, and "pola has fewer side effects"; secondly, it is based on the characteristics of the drug itself, "r is a cd20 monoclonal antibody, and pola is the world's first antibody conjugate (adc) targeting cd79b. the drug molecule consists of three parts: antibody, linker and cytotoxic drug. the antibody has a high affinity for the cd79b antigen widely expressed on the surface of b lymphocytes, which can achieve precise positioning; at the same time, it has a killing effect on tumor cells. after the antibody targets b lymphocytes, it releases highly lethal cytotoxic drugs through lysis, inducing tumor cell apoptosis."

yuhao's physical condition also confirmed the relatively good results.

"after i got the drip that day, i told my parents that i felt much better. apart from being a little tired and wanting to sleep, everything else was fine." yuhao recalled the first treatment. he didn't feel particularly uncomfortable. he still went to class as usual during the day. evening self-study was cancelled at the request of his parents, so he had more time to rest. on the night after the college entrance examination, his parents told yuhao about his condition. he was not surprised. "i knew i wasn't well, but i didn't know it was so serious." the next day, his parents took him to the hospital and started formal treatment.

yuhao is preparing for the exam. photo/provided by the interviewee

"his ldh (lactate dehydrogenase) was very high before, and the tumor growth index was also very fast, but the disease did not progress in the more than 20 days after the first medication." zhang xiaoping immediately started to use the pola-r-chp combination regimen for yuhao. the treatment was carried out according to a 21-day course of treatment (7 days of medication + 14 days of recovery). after completing three courses of treatment in mid-august, yuhao was evaluated again in the middle of the year.

according to the deauville lymphoma scoring system, yuhao's mid-term evaluation result showed a score of 3, which means that although there are still some residual masses in the body, there is no tumor activity. "according to pet-ct, he has achieved complete remission, which is a very good therapeutic effect." at the same time, zhang xiaoping is also optimistic about yuhao's follow-up treatment.

she mentioned that a previous phase iii polarix study based on the pola-r-chp treatment regimen (the study was a global, multicenter, randomized, double-blind, placebo-controlled clinical trial that included 879 patients），the results showed that compared with the control group, the 2-year progression-free survival (pfs) rate of the pola-r-chp group reached 76.7%.⁵"the proportion of patients who were free of relapse at 2 years in the pola-r-chp group was higher. if patients can maintain a sustained remission after first-line treatment, they will have a greater chance of being cured."

yuhao is also full of hope that he may be cured. "now i am not particularly afraid of this disease. i just listen to the doctor and my parents. they said i can be cured, so i don't care about anything else." the only regret is that on the first night of the college entrance examination, he did not listen to his parents' advice and insisted on taking a walk as usual without knowing his actual condition, which made him extremely tired. when he took the physics test the next day, he always felt that "the questions were right in front of him", which led to his unsatisfactory performance.

looking forward to benefiting more patients

because of the side effects of chemotherapy drugs, yuhao is particularly concerned about his hair. he feels that his hair is constantly falling out, "i'm afraid i'm going bald." but zhang xiaoping frankly said that yuhao is relatively lucky. the chemotherapy drug in pola-r-chp has been selected for him, which is liposomal doxorubicin with relatively fewer side effects. if it had been ordinary doxorubicin, his hair might have fallen out.

"but in most cases, not every patient can afford pola-r-chp in our actual clinical practice." zhang xiaoping did some calculations. because pola has not yet been included in medical insurance, patients can only use it at their own expense. a patient needs to be injected with at least 3-4 injections of pola, which is 30,000-40,000 yuan. six courses of treatment is a complete treatment cycle, which requires the patient to pay about 200,000 yuan.

therefore, even though pola-r-chp has been recommended as a grade i treatment for patients with newly diagnosed dlbcl in the 2024 csco lymphoma diagnosis and treatment guidelines, in actual clinical practice, pola-r-chp is not necessarily the first choice for doctors. first-line treatment options need to be recommended based on the patient's actual economic situation.

taking the zhongda hospital affiliated to southeast university as an example, zhang xiaoping introduced that not many patients in their hospital use pola-r-chp as the first-line treatment. zhang xiaoping mentioned that there was a dlbcl patient in his 20s who did not choose pola-r-chp as the initial treatment plan. although he achieved complete remission at that time, he relapsed during the follow-up examination six months later. "he was engaged to a girl before he was diagnosed. the girl's father was a little dissatisfied when he heard that he was ill. now he has relapsed again, and he is very upset. and a lot of money he spent before is equivalent to wasted, and he has to start all over again (treatment)."

the battle against cancer is a war without the smoke of gunpowder. it requires not only personal persistence and will, unconditional support and protection from the family, but also innovation in medical technology to bring new hope to patients. on the other hand, the accessibility of drugs is equally important. if the economic burden of treatment becomes an unbearable burden for many patients and their families, the significance of advanced treatment options will be greatly reduced. as zhang xiaoping said: "pola has a good prospect. if it can be included in medical insurance, we will recommend it to more suitable patients, and patients will benefit more."

yuhao rides his beloved bicycle again. photo/provided by the interviewee

of course, any drug treatment plan or advanced treatment method is a post-emergence response after the disease occurs, and it is still at the "bottom" in the health management system. for us, the best measure for any disease management is still "prevention". zhang xiaoping specifically mentioned that dlbcl patients are mainly middle-aged and elderly patients. although 19-year-old yuhao is an "accident", there is actually a trend of younger people. this is related to people's long-term staying up late, excessive exercise, excessive physical overdraft, and psychological pressure leading to decreased immune function.

she suggested that people should never overdraw their youth and should not stay up late just because they think they are still young. in addition, people should exercise in moderation and within their ability, avoid sitting for long periods of time, maintain a healthy lifestyle, and pay attention to improving their immunity.

starting tomorrow, yuhao will start his new life. in addition to continuing to cooperate with the treatment, he said that he has become more "healthy" now, no longer stays up late, does not lose his temper easily, and keeps a good mood. after all, with a good body, all good things and possibilities will follow.