After Multiple Lines of Treatment and Four CAR-T Therapies, Her Disease Still Progressed - She and Her Doctors Are Still Looking for What Comes Next

Follicular LymphomaCAR-T2026-08-21

Summary: In 2020, 41-year-old Ms. Wang (pseudonym) was diagnosed with Grade 3A, Stage IV follicular lymphoma with bone marrow involvement. Over the years that followed, she received chemotherapy, targeted and immunotherapy combinations, clinical-trial treatment, antibody-based therapy, radiotherapy, and multiple CAR-T cell therapies, yet the disease continued to relapse and progress. After she came to Beijing GoBroad Boren Hospital in 2025, Dr. Yajing Zhang and her team reviewed her entire treatment history and repeatedly adjusted the strategy according to tumor burden, target expression, blood counts, and her overall condition. Along the way, autologous CAR-T cells failed to expand effectively, universal CAR-T responses were not durable, and massive splenomegaly and thrombocytopenia became new barriers to treatment. Through splenectomy, CD22 CAR-T, and subsequent sequential treatment, the team kept creating conditions for the next step. Ms. Wang is still receiving treatment and being monitored closely today. Her story is a real account of long-term treatment, repeated reassessment, and the continuing search for another possibility.

Rapid Progression After First-Line Treatment Made Her Realize This Would Be a Long Journey

In the summer of 2020, 41-year-old Ms. Wang sought medical care for persistent abdominal pain and fever.

After ultrasound, CT, PET-CT, and a pathology biopsy, she was diagnosed with Grade 3A, Stage IV follicular lymphoma with bone marrow involvement.

After diagnosis, she received six cycles of R-CHOP followed by two courses of rituximab maintenance. Early follow-up showed a marked reduction in disease, and for a while Ms. Wang thought that once treatment was over, life might finally return to normal.

But not long after completing treatment, new lymph nodes appeared and abnormal findings returned in the bone marrow. The disease was progressing again.

Over the next several years, she enrolled in clinical trials and received therapies with different mechanisms, including targeted and immunotherapy combinations, chemotherapy, antibody-drug conjugate therapy, and splenic radiotherapy.

Some treatments brought a short period of remission. Others showed progression again after only one or two cycles.

For Ms. Wang, the hardest part was not any single piece of bad news. It was the repeated cycle of "just starting to see hope, then having to change course again."

After Three Universal CAR-T Treatments, the Disease Still Could Not Be Controlled for Long

In 2023, Ms. Wang's disease progressed significantly again. On the advice of other patients, she began learning about CAR-T cell therapy.

During evaluation, her own T cells were found to be in poor condition, so autologous CAR-T could not be manufactured as originally planned. She therefore received universal CD19 CAR-T therapy.

After the first infusion, she developed persistent high fever and shortness of breath. One month later, however, follow-up showed a complete metabolic response. Unfortunately, the remission did not last long. Abnormal findings soon returned in both bone marrow and imaging studies.

In 2024, Ms. Wang received a second and then a third universal CD19 CAR-T treatment. Each brought a period of response, but the disease never achieved stable, long-term control.

By early 2025, fever, fatigue, and enlarged lymph nodes had returned. Tests showed involvement of multiple lymph nodes, the spleen, and bone marrow, with abnormal cells also appearing in peripheral blood.

At the same time, years of treatment had reduced both the number and function of her lymphocytes, while her platelet count remained low. Treatment options were narrowing, and her body had less reserve to tolerate further therapy. At that point, her previous attending doctor recommended that she travel to Beijing GoBroad Boren Hospital for further evaluation by Dr. Yajing Zhang and her team.

At Beijing GoBroad Boren Hospital, the Team First Reconstructed Her Entire Treatment History

Ms. Wang first met Dr. Yajing Zhang at the end of February 2025. Rather than focusing only on the latest test report, the team began by reviewing her pathology, every previous treatment, and the pattern of each response and progression since diagnosis.

At this stage, the question was no longer simply, "What drug is left to try?" The team needed to address several issues at the same time:

How high is the current tumor burden?
Which treatment targets are the tumor cells still expressing?
Are the patient's own lymphocytes still suitable for another attempt at cellular therapy?
What level of treatment can her blood counts and overall condition still tolerate?
Could the treatment chosen now limit options later?

After a comprehensive assessment, the team initially aimed to reduce the tumor burden and create the conditions for another attempt at autologous CD19 CAR-T therapy.

After lymphocyte collection, tumor-reduction treatment, and lymphodepleting conditioning, Ms. Wang received an autologous CD19 CAR-T cell infusion on April 7, 2025.

Autologous CAR-T Cells Failed to Expand, So the Team Quickly Looked for a New Treatment Window

After the CAR-T infusion, repeated monitoring showed no effective cellular expansion. Even after pomalidomide was used in an attempt to stimulate expansion, the expected response did not occur.

For Ms. Wang, this was another heavy blow. But the team did not stop at the conclusion that the treatment had "failed." Based on her disease status and the narrow treatment window at the time, they moved promptly to universal CD19 CAR-T on day 12 after the autologous infusion.

The new CAR-T cells did expand in her body. Ms. Wang developed high fever, capillary leak syndrome, diarrhea, and low blood pressure, but with close monitoring and supportive care, these problems gradually stabilized. Her spleen shrank substantially, and her blood counts also improved.

Even so, the effect of this CAR-T treatment did not last. Subsequent monitoring again showed no sustained cellular expansion, further attempts at stimulation did not produce the hoped-for response, and her platelet count continued to fall.

Treatment had reached another crossroads.

Massive Splenomegaly and Low Platelets Became the Next Bottleneck - Splenectomy Reopened the Path to Treatment

As treatment continued, Ms. Wang's massive splenomegaly and thrombocytopenia increasingly became major barriers to the next stage of care.

The spleen continued to enlarge. This reflected the tumor burden, while also interfering with recovery of her blood cells.

With platelets too low, many treatments could not be given safely.

After repeated assessment, Dr. Yajing Zhang's team concluded that treating the spleen was not simply about solving a local problem. More importantly, it could create new room for subsequent treatment.

The team actively coordinated with a partner hospital in the medical network to move the surgical plan forward.

On May 26, 2025, Ms. Wang successfully underwent total splenectomy. After surgery, her blood counts and overall condition gradually improved. Fever and night sweats eased, her weight began to recover, and most importantly, she became physically able to continue treatment.

For Ms. Wang, the surgery also helped her understand something important: long-term treatment is not about continuously adding more drugs. At each stage, the team first has to identify the problem that most limits the next step - and address that problem first.

As Tumor Targets Changed, the Treatment Strategy Changed with Them

After splenectomy, follow-up still found a small number of abnormal B cells in the bone marrow and peripheral blood. Because the tumor cells were still expressing CD22, the team decided to try CD22 CAR-T therapy.

After the July 2025 infusion, the CAR-T cells initially expanded but soon became undetectable again. Drug-based stimulation and reinfusion of the remaining cells also failed to produce a durable effect.

Over the following months, the disease continued to fluctuate. The team repeatedly adjusted targeted therapy, antibody therapy, and cellular immunotherapy based on peripheral blood tests, bone marrow examinations, PET-CT, and reassessment of tumor targets.

Sometimes the abnormal cells fell and then rose again. Sometimes a new combination worked briefly but could not maintain the response.

Ongoing treatment was also changing the tumor itself. CD19 expression had shifted, which meant that approaches that had worked before - or had once seemed theoretically possible - could not simply be repeated.

Ms. Wang gradually came to understand why the doctors kept repeating bone marrow tests, blood tests, and target-expression testing.

They were not treating an unchanging disease called "follicular lymphoma." They were treating a disease that could evolve under treatment pressure.

Every Time the Disease Progresses, Four Questions Need to Be Asked Again

For a patient with relapsed or refractory disease like Ms. Wang, every progression requires the team to reassess four questions:

Where is the disease mainly active now?

Is it in the bone marrow, spleen, lymph nodes, or several sites at the same time?

Which targets are the tumor cells expressing now?

Are targets such as CD19 and CD22 that were previously usable still present?

What treatment can the patient tolerate at this point?

Platelet count, immune function, organ status, and damage from previous therapies can all change what is feasible next.

Could this step affect the options that come after it?

Treatment needs to control the disease as much as possible while also preserving the patient's ability to move on to the next stage of care.

In May 2026, testing again showed disease progression, with a higher proportion of abnormal cells in the bone marrow and new lesions on PET-CT. Instead of repeating approaches that had already stopped working, the team used the latest target-testing results to switch to inotuzumab ozogamicin combined with targeted therapy.

After the first cycle, abnormal cells in peripheral blood fell markedly. At the June follow-up, peripheral blood immunophenotyping temporarily showed no abnormal population.

The treatment also caused a further drop in platelets, so the team adjusted the treatment schedule again and replanned the next steps. This was still not the endpoint, but it showed that even as the disease changed, there were still directions worth exploring.

In Long-Term Treatment, It Is Not Only About the Tumor - It Is Also About Whether the Patient Can Keep Going

Over the years, Ms. Wang has already gone through many different treatments. In addition to the disease itself, she has had to deal with repeated testing, treatment side effects, financial pressure, and the psychological impact of one progression after another.

One thing she values about working with the team is that the doctors do not look only at tumor markers on a report. They also ask whether she can still eat, sleep, and move normally; whether her blood counts can support the next treatment; and whether the financial and physical burden of the current plan is manageable. Dr. Yajing Zhang once even gave her a small duck mascot nicknamed "Turn Negative" - a lighthearted good-luck charm for better test results.

Whenever a test result is disappointing, the team explains why the plan needs to change and what options may still remain, rather than simply saying, "We will try another regimen." That kind of understanding and communication has helped Ms. Wang keep moving forward after repeated setbacks.

She Is Still in Treatment, but She No Longer Treats Every Test Report as a Final Verdict

Ms. Wang's weight has now recovered from a low of about 45 kg to more than 55 kg. Her energy, stamina, and appetite have also improved compared with when she first arrived at the hospital.

She is still receiving treatment and undergoing dynamic follow-up. The disease has not ended, and there is still considerable uncertainty. But unlike before, she no longer sees the next test report as a "verdict" that decides everything.

Looking back over the past six years, there are three things she most wants to share with other patients:

Q: If one treatment does not work as expected, does that mean there are no other options?

Not necessarily.

In relapsed or refractory lymphoma, disease status, target expression, and the patient's physical condition can all change after each treatment. The next step needs to be based on a new assessment.

Ms. Wang has experienced multiple treatment challenges: failure of autologous CAR-T cells to expand, a universal CAR-T response that was not durable, and only brief expansion after CD22 CAR-T. Each time, the team returned to the latest test results to look for another potentially usable treatment direction.

Q: Why does relapsed or refractory lymphoma require repeated target testing?

Because the tumor does not stay the same.

Ongoing treatment can create selective pressure on the tumor, changing target expression and clonal composition. A target that was present before may later decrease or change, so after progression the treatment direction needs to be reconsidered using updated test results.

Q: During long-term treatment, what matters besides controlling the tumor?

Blood counts, infection, organ function, nutrition, physical strength, and whether the patient can tolerate the next stage of treatment all matter.

For patients with complex relapsed disease, keeping the patient well enough to remain eligible for treatment - and creating an opportunity for the next effective intervention - is itself an important long-term goal.

Case Commentary by Dr. Fangfang Cheng, Attending Physician: Ms. Wang has a typical case of relapsed or refractory follicular lymphoma, but the difficulty of her treatment is substantially greater than in many other patients who have relapsed after multiple lines of therapy. She has had a long disease course and many prior lines of treatment, with recurrent involvement of the bone marrow and spleen. By the time she transferred to our hospital, she had a high tumor burden together with significant thrombocytopenia, impaired immune function, and poor lymphocyte quantity and function. These factors not only affect drug efficacy; they also directly limit cell collection, manufacturing, expansion in the body, and the range of subsequent treatment options. The team first reduced the tumor burden to create better conditions for cellular therapy. When the autologous CD19 CAR-T cells failed to expand effectively, we used the treatment window available at the time to transition promptly to universal CD19 CAR-T, which temporarily improved both splenomegaly and blood counts. Later, massive splenomegaly and thrombocytopenia became the main barriers to continuing treatment, so the team facilitated total splenectomy. After surgery, her fever, night sweats, blood counts, weight, and quality of life all improved, and she became physically able to proceed with CD22 CAR-T and subsequent sequential therapy. Since then, we have continued adjusting treatment according to peripheral blood, bone marrow, imaging, and target-expression results rather than mechanically repeating previous regimens. A recent new treatment led to a marked drop in abnormal cells in peripheral blood, but close dynamic follow-up is still needed. This case shows that the goal in complex relapsed disease cannot be reduced to any one drug or any one cell infusion. The more important task is to identify the key problem at each stage, control the tumor while managing infection, blood counts, and organ function, and preserve the patient's treatment fitness as much as possible so there is still an opportunity for the next effective intervention. The long-standing trust, understanding, and cooperation of the patient and her family have also been essential in allowing this journey to keep moving forward. Commentary by Dr. Yajing Zhang: Do Not Predetermine the Endpoint - Keep Looking for Better Options as the Disease Changes Follicular lymphoma is generally considered an indolent lymphoma with a relatively slow course and multiple treatment options. But having "many options" does not mean that every patient will achieve a long and stable remission. Ms. Wang had Stage IV disease with bone marrow involvement at diagnosis and progressed soon after first-line immunochemotherapy. Her responses to several subsequent treatments with different mechanisms were short-lived, showing that her lymphoma had strongly refractory features. As the number of prior treatments increased, she gradually developed a high tumor burden, massive splenomegaly, bone marrow involvement, thrombocytopenia, immunoglobulin deficiency, reduced lymphocyte number and function, and changes in tumor targets and phenotype. The team was therefore not facing a single question of "which drug should we choose?" We were dealing with a system in which disease biology, damage from previous treatment, and the patient's overall ability to tolerate therapy were all intertwined. For a patient like this, treatment cannot be understood as a series of isolated regimens, and hope cannot be placed entirely on any single cell infusion. The core approach is full-course sequential management: first identify the most important problem at the current stage, then consider how tumor reduction, targeted therapy, antibody therapy, cellular therapy, surgery, and supportive care can work together to create the conditions for the next step. When Ms. Wang's autologous CD19 CAR-T cells failed to expand effectively, we used the treatment window at that time to transition promptly to universal CAR-T, which still produced meaningful splenic shrinkage and improved blood counts. The subsequent splenectomy was not simply a replacement for drug therapy. It was intended to relieve the bottleneck created by massive splenomegaly and blood-cell consumption, improve her overall condition, and reopen treatment options. Another defining feature of relapsed or refractory lymphoma is that the tumor is not static. Treatment creates selective pressure. Target expression, clonal composition, and the tumor microenvironment can all change as a result. That is why every progression requires a new assessment rather than a plan based only on the original pathology label or previous target results. The team must keep asking four questions: ·Where is the disease mainly active now? ·What are the tumor cells expressing now? ·What can the patient tolerate now? ·Could this treatment step affect what can be done next? Cellular therapy also cannot be judged only by whether a target is present. Cell source and quality, the effect of prior treatment on T cells, whether the cells can expand and persist in the body, tumor burden, the immune microenvironment, and infection risk can all influence the outcome. Failure of one cell product to expand does not mean that every cellular therapy will fail. Likewise, one remission does not mean that monitoring can stop. True individualized care means putting all of these variables on the same treatment map and reprioritizing them as the patient's condition changes, rather than simply stacking one therapy on top of another. The team also pays close attention to the patient's overall condition. Beyond disease control, the ability to eat, sleep, and remain active; whether blood counts can support the next treatment; whether infections can be prevented; whether the patient understands the plan; and whether the financial and psychological burden is manageable all influence how far long-term treatment can go. "Not giving up" does not mean promising that every treatment will work, and it does not mean adding more therapy when there is no evidence to support it. As long as the patient still wishes to continue and there remains a medically reasonable opportunity to intervene, the team will keep looking for a more appropriate next step through scientific assessment, risk control, and full communication. Even when treatment needs to slow down, we try to preserve the patient's ability to keep living - and to keep having choices. For relapsed or refractory lymphoma, the most meaningful kind of persistence is to keep identifying problems as they change, create the conditions for the next step, and continue walking this long road together with the patient.

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