A second complete remission after myeloma relapse

The mass in Lucy's abdomen had begun to shrink. For a short while, it seemed the latest treatment was working.

After two cycles of salvage therapy, her myeloma had reached a partial response. About a week later, blood markers began rising again. She had barely recovered from the treatment before she was back in the consulting room, discussing what came next.

This time, she did not begin by asking when the next cycle would start.

“Is there another option?”

Lucy was 61 when she was diagnosed with multiple myeloma in July 2020. She had pain in her chest, back and ribs, as well as fatigue, weight loss and anemia.

In retirement, she had liked arranging her own days: running errands, seeing friends, doing things without asking her family for help. As she became ill, a trip out required more thought. Jobs she once finished in one go had to be spread out.

She struggled to explain the change. If someone asked, she would say she was a little tired. Describing how much effort an ordinary day took was harder.

The diagnosis introduced her to a disease she knew little about. Myeloma begins in plasma cells in the bone marrow. These cells normally help the body fight infection; when they become cancerous, they can damage bone and interfere with the production of healthy blood cells. Her disease was advanced, and genetic testing found several high-risk abnormalities.

The doctors discussed an autologous stem cell transplant, which would use her own blood-forming stem cells. She declined.

She wanted treatment, but had concerns about what the procedure would involve, how much her body could take and how recovery might go. Being told to keep going for the sake of getting better did not answer those questions. She wanted to understand the options and have a say in the decision.

She received bortezomib, doxorubicin and dexamethasone. After six cycles, her disease reached complete remission.

While the doctor went over the next steps, she found herself thinking of things she had put off because of pain and exhaustion. When a friend suggested meeting, she could consider whether she wanted to go before thinking about treatment.

Four cycles of consolidation therapy followed, then maintenance treatment. Some drugs proved difficult for her to tolerate, and the doctors adjusted the regimen.

She became better at describing how she felt. Before an appointment, she would think through what had been hardest: which symptoms interfered with eating or sleeping, which made it difficult to leave home. She had once worried that saying too much would sound like complaining. Now she understood why the doctors needed to hear it.

In May 2023, the tests changed.

The M-protein associated with her myeloma became detectable again, and other markers of disease activity continued to rise. She then noticed a lump in her lower right abdomen. Imaging showed a mass in the right side of her pelvis, almost 13 centimeters at its longest point.

Until then, much of her understanding of myeloma had come from blood tests, bone marrow examinations and bone pain. The abdominal mass was something she could feel. Sometimes she found herself putting a hand over it, then pulling away, knowing she could not judge what was happening by touching it.

A biopsy showed plasmablastic features and very rapid cell growth. The disease had formed a tumor outside the bone marrow and was behaving aggressively.

At the same time, the proportion of plasma cells in her marrow was relatively low. This confused her. The doctors had to consider the scans and tissue findings together; the marrow result alone did not reflect the extent of this relapse.

A new combination of drugs was prescribed at reduced doses because of her tolerance. Even so, she developed severe neutropenia, a shortage of infection-fighting white blood cells, with fever.

She found it difficult when people told her to “hang in there.” She knew they meant well. She was willing to continue, but wanted to know whether what she was enduring might buy her more than a brief response.

After two cycles, the mass was smaller and the disease met the criteria for a partial response. About a week later, the markers rose again.

The team now had to contend with fast-moving disease, short-lived benefit from treatment and her poor tolerance of further chemotherapy. She remained unwilling to have an autologous stem cell transplant.

Another test offered a possible way forward. Her bone marrow cells showed substantial expression of BCMA, a protein that can be targeted by CAR-T cells.

The doctors described a process that would begin with collecting T cells from her blood. The cells would be modified in a laboratory so they could recognize the target, then infused back into her body to attack the cancer.

She understood that the treatment would use her own immune cells. That did not make the decision simple. Previous treatments had worked before the disease returned. She wanted to know what would happen while the cells were being prepared, what the team would watch for after infusion and how complications would be managed.

After discussing the risks of her disease, the limited alternatives and the possible benefits and adverse effects of CAR-T therapy, she decided to proceed.

Her T cells were collected in November 2023. While they were being prepared, she received five sessions of radiotherapy to the remaining abdominal mass as a bridge to CAR-T treatment.

The mass did not change appreciably in size.

She had hoped to see it shrink before the infusion and was disappointed. For now, the tumor was still there, and the next stage of treatment remained ahead of her.

She received three days of preparatory chemotherapy. On January 9, 2024, the modified CAR-T cells were infused.

Afterward, she developed grade 2 cytokine release syndrome, an inflammatory reaction associated with CAR-T therapy. It lasted about five days and was treated with tocilizumab and other measures. Her neutrophil and platelet counts also fell.

She did not develop the associated neurologic toxicity syndrome. Her low blood counts recovered over roughly three months.

At the first formal assessment, one month after infusion, the tumor had shrunk enough for a partial response.

Lucy was pleased, but cautious. She remembered how quickly the last improvement had been followed by rising markers. She wanted to see what the next scan would show before sharing the news widely.

At three months, PET/CT and other assessments showed complete remission.

She had heard those words once before. This time, she knew both their value and their limits. First she asked about medication, follow-up appointments and the changes she should report. After the doctor had finished, she allowed herself to enjoy the result.

Because her disease was high-risk, the team started pomalidomide maintenance treatment at about three months after infusion, hoping to prolong the remission.

Around 15 months after CAR-T therapy, she remained in stringent complete remission, a particularly deep response. Testing for minimal residual disease was negative: no tiny traces of disease were found within the sensitivity of the test.

It was a sustained remission, not proof of a cure. But after the rapidly growing abdominal tumor and the brief response to salvage therapy, she had time to think beyond the next treatment.

She began answering invitations differently. Where she had once said, “Maybe another time,” she now asked about the time and place, then checked her medical appointments. If she was not up to going, she could say so.

One day a friend mentioned a place where they could take a gentle walk together.

Lucy asked how far away it was and whether there were places to sit along the way. Once she had her next follow-up appointment arranged, she said, they could settle on a date.