The blood cancer that became solvable

Multiple myeloma is brutal. We may finally have a cure, but American inertia meant that it was discovered in China.

Ruxandra Teslo and Amol Punjabi explain why more and more drugs are being developed in China.

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Multiple myeloma is among the most painful of all cancers. The disease originates in the bone marrow, where a single abnormal plasma cell, one of the blood cells that normally fights against infection, begins to proliferate uncontrollably, crowding out healthy blood-forming cells. In doing so, multiple myeloma destroys the bone from within.

Healthy bone is maintained by a perpetual exchange between osteoclasts, which dismantle old bone, and osteoblasts, which rebuild it. Myeloma disrupts this equilibrium, accelerating the action of osteoclasts and silencing that of osteoblasts – more bone is dismantled and less is rebuilt. The spine is especially exposed: its vertebrae bear the body’s weight and harbor the marrow in which myeloma thrives. As they are eroded from within, the result is a persistent ache, unrelieved by rest and often worse at night. As the disease advances, weakened vertebrae may collapse under the simple burden of standing upright, adding acute fracture pain to a chronic background ebb.

Multiple myeloma can damage bone, especially the vertebrae in the spine, leading to severe pain and impaired mobility. Image credit: Ruxandra Teslo.

During the twentieth century, cancer treatment rested on three pillars: surgery, radiotherapy, and chemotherapy. Surgery has been used against tumors since antiquity and radiotherapy since the discovery of X-rays in the 1890s. Chemotherapy, the newest of the three, was developed in the 1940s and 1950s, its origins tracing back to observations about mustard gas during the Second World War.

These therapies were developed before anyone understood cancer at a molecular level. Blunt and often brutal tools, they work by exploiting the fact that cancer cells tend to divide faster than normal ones, and then doing something destructive enough to kill dividing cells preferentially. And while these treatments can cure some cancers discovered at an early stage, they offer little hope of a real cure for more advanced or relapsed cases.

Then, in the mid-2010s, a new class of genuinely transformative drugs arrived: immunotherapies. These treatments recruit the body’s own immune system to recognize and destroy malignant cells. The results, particularly in metastatic and relapsed disease, have been extraordinary. Multiple myeloma is one of the cancers that illustrates this most vividly, with the immunotherapy Carvytki, which was first approved by the FDA in 2022 for patients who had returning disease after four or more lines of therapy. Carvykti marks a turning point in the treatment of multiple myeloma for two reasons. First, unlike the conventional approach, in which patients endure continuous cycles of treatment, remission, and relapse for the rest of their lives, it is administered as a single, one-time infusion. Second, it is producing something that has never before been seen in this disease: durable, long-term remissions in patients which had been refractory to several other treatments, raising the possibility of a cure.

But Carvykti matters beyond multiple myeloma. In retrospect, its development story, which began in 2016, was an early signal of a transformation that is only now, a decade later, making headlines: the United States is beginning to lose its dominance in drug discovery to China. The foundational science behind Carvykti was largely American, but the therapy that changed the field came from a Chinese company that moved quickly from idea to patient. If the US does not address the regulatory and clinical-trial bottlenecks that slow the generation of early in-human data, more breakthroughs like Carvykti will be developed elsewhere, weakening the ecosystem on which American biopharma depends.

The brutality of myeloma treatment

The treatment regimen for multiple myeloma is particularly brutal, even compared to other cancers. Under the newest standard approach, it often begins with months of induction therapy built around four drugs: daratumumab, an antibody that marks myeloma cells for immune attack; bortezomib, a proteasome inhibitor injected under the skin; lenalidomide, an immunomodulatory drug taken as a pill; and dexamethasone, a steroid powerful enough to restructure the rhythm of every week.

Patients come in and out of the clinic for injections, take pills at home and undergo repeated blood tests, living according to a calendar organized around treatment days and recovery days. They also have to contend with the side effects of the medications. Dexamethasone can produce a sleepless agitation followed by a physical and emotional crash. Bortezomib often damages peripheral nerves, causing tingling and a burning pain in the hands. Daratumumab often leads to immune suppression, leaving patients more vulnerable to infections.

For patients fit enough to withstand it, this induction regimen is followed by a stem cell transplant. This begins with high-dose chemotherapy that destroys the bone marrow entirely, followed by weeks of isolation with no functioning immune system and a recovery that continues for months after discharge. This stage is accompanied by repeated infections, extreme fatigue and mucositis, a painful inflammation of the digestive tract lining from mouth to gut. Patients are also profoundly vulnerable to even ordinarily minor pathogens that would pose no risk in a healthy person. After the transplant, the patient still has to do lenalidomide maintenance.

What is worse is that even after this brutal treatment most patients relapse, meaning their cancer returns. For these patients, what follows is further cycles of treatment. Doctors start patients on new combinations of drugs, including proteasome inhibitors and more chemotherapy. While these combinations can lead to remission, the myeloma almost always relapses again, leaving patients with progressively fewer options. Each treatment cycle means a lower possibility of survival.

Then there is quality of life. Many of the therapies for relapsed multiple myeloma are administered with intravenous injections or infusions and are given frequently, even weekly. For most patients, a one-time shot would represent a major improvement for their quality of life, even if efficacy were the same. What if the one-time shot also prolonged survival by years and appeared to cure relapsed cancers completely in a proportion of patients? This is what CAR-T therapies like Carvykti can offer.

My other car is a T cell

CAR-T therapies make clever use of a patient’s own immune system. T cells, a type of immune cell that can attack tumours, are first extracted from a patient’s blood. Then, they are shipped to a manufacturing facility where they are genetically re-engineered to carry a new receptor on their surface. This is a chimeric antigen receptor, abbreviated as CAR, which is designed to recognize and bind to a specific protein on cancer cells.

The modified cells are then cultured until there are hundreds of millions of them, before they are frozen and shipped back. After a short course of chemotherapy to clear space in the immune system, they are infused back into the patient. From that point, the CAR-T cells are free to seek out cells carrying their target protein and destroy them. Because they are living cells rather than inert drugs, they can persist, proliferate, and continue hunting for months or years.

Multiple myeloma is perfectly suited to this approach for two reasons. First, because multiple myeloma is a blood cancer. Unlike solid tumors which form dense, poorly vascularized masses that T cells struggle to penetrate, myeloma cells circulate through the bone marrow and bloodstream. They are, in the language of immunotherapy, accessible. The same feature that makes blood cancers so difficult to surgically remove makes them unusually vulnerable to a therapy that travels through the blood to find its target.

The second reason comes from a protein called B cell maturation antigen, or BCMA. The fundamental challenge of any targeted cancer therapy is selectivity: the ability to kill tumor cells without destroying healthy ones. Most oncology targets are imperfect in this regard, expressed on tumor cells at elevated levels but present in healthy tissue too, which limits how aggressively they can be pursued. BCMA was first identified in 1992 by a French research group led by Yves Laabi. Laabi’s group were trying to find genes preferentially expressed in mature B cells, but had no idea what use to put their discovery to.

For most of the decade following its discovery, BCMA sat in relative scientific obscurity: an interesting receptor without an obvious clinical application. But researchers gradually began to understand that BCMA was expressed at high levels on malignant plasma cells in multiple myeloma and that it was largely absent from most other tissues in the body.

In 2013, preclinical data from the lab of James Kochenfelder at the National Cancer Institute showed that BCMA-targeted CAR-T cells were effective against myeloma cells in the laboratory. But what followed illustrates the enormous and often underappreciated gap between a promising laboratory finding and a treatment that reaches patients.

CAR-T targeting a cancer cell via BCMA recognition. Image credit: Sun et al.

The importance of being llama

Today, there are two CAR-T cell therapies for multiple myeloma in the US market: Abecma, approved in 2021, and Carvykti, approved in 2022. Both target BCMA on the surface of myeloma cells. Yet they arrived by strikingly different routes: Abecma from American research institutions and corporate laboratories in the early 2010s; Carvykti from an early-stage biotechnology company and a clinical trial first conducted in China in 2016. Only later was it licensed to a Western company and eventually brought to global approval.

Of the two, Carvykti is the clear winner. Its story speaks to the outsized role that China’s 2015 regulatory reforms have played in accelerating the country’s path from laboratory to clinic, and to producing medicines that work. Being first to market or doing the fundamental science counts for far less than being the nimblest in getting to the clinic. Carvykti also carries another important lesson for the industry: never underestimate the llama.

The technology developed in Kochenfelder lab was licensed to the biotech start-up Bluebird Bio, which developed it in partnership with the large biopharmaceutical company Bristol Myers Squibb into what would eventually become Abecma, the first CAR-T therapy approved for multiple myeloma. Over 80 percent of patients saw their cancers shrink in the National Cancer Institute’s first-in-human trial, published in 2016. This validated the premise of BCMA targeting and set the field moving.

Meanwhile, a parallel story was unfolding on the other side of the world. In 2014, a team of Chinese scientists began investigating cell therapies for cancer, initially working in what the company describes as a room the size of a freight elevator. After focusing their research solely on BCMA-targeting CAR-T cells in 2015, Legend Biotech began conducting its first clinical trials in 2016.

Central to their approach was a significant departure from convention. Traditional CAR-T constructs relied on using existing antibody fragments, derived from humans, to seek out and bind to their target protein; in this case, BCMA. Legend took a different path, turning to an unlikely source: the llama. Human antibody fragments almost always bind to at least two targets, meaning that if doctors give a patient too much of the drug, they risk causing side effects associated with the second protein the drug binds to.

Camelid animals, including llamas and alpacas, produce a unique class of antibodies known as nanobodies, which can be engineered to do the work of their much larger human counterparts. Their compact size and remarkable stability allow CAR-T cells armed with them to target tumors more efficiently. CAR-T cells using nanobodies also seem to stay active longer and kill tumors more effectively.

The Chinese researchers enrolled their first patient in a clinical trial in 2016, the same year the American team published their initial results. But they moved fast. By 2017, just a year later, they were presenting stunning data at one of the biggest conferences in the field. The decision to learn from the llamas seemed to have massively paid off.

Xi loves you (yeah, yeah, yeah)

It can take years for enough people in a cancer trial to die to clarify that one treatment is prolonging survival over another, so researchers rely on proxies instead. In the American trial, 80 percent of patients responded to treatment, meaning their tumors shrank to some measurable degree, a result already considered impressive given how much these patients had already been treated, to no avail. The Chinese trial did better: every single patient responded. What’s more, 74 percent of patients in the Chinese trial saw their cancer completely wiped out, compared to 56 percent in the American equivalent.

Such results did not go unnoticed. Within months of the 2017 presentation, Janssen Pharmaceuticals, the pharmaceutical subsidiary of the large American company Johnson & Johnson, was in negotiations with Legend Biotech. In December 2017, the two companies announced a global licensing and codevelopment agreement: Legend got $350 million upfront plus half of any revenue generated in the US, while also contributing to half of the development costs.

After years of clinical development, later-stage trial results confirmed what earlier data had suggested: Carvykti was the superior treatment. In later stage trials, oncologists and regulators switch from looking at how many patients respond at all to looking at progression-free survival, or the length of time a patient lives without their disease worsening or claiming their life. The gold standard is overall survival, but it is also the hardest to measure, requiring trials long enough to capture the full arc of a patient’s outcome. For that reason, regulators often grant approval on the basis of progression-free survival data, with overall survival figures following later as evidence accumulates.

On both measures, Carvykti pulled clearly ahead. In the CARTITUDE-1 trial, its 12-month progression-free survival rate was 76 percent. In the KarMMa trial for Abecma, by contrast, this figure was 55 percent. But what happened afterwards is perhaps even more striking: in the Abecma progression free survival curve, the line falls continuously. By contrast, in Carvykti, the line starts to plateau. Extended follow-up at five years confirmed that 33 percent of Carvykti patients remained disease-free. The significance of this result cannot be overstated. These were patients for whom, on average, four prior lines of therapy had already failed and whose immune systems were heavily challenged.

The CARTITUDE-1 trial results led to Carvytki’s approval in 2022 for patients with myeloma who have failed four other lines of treatment. In 2024 the FDA approved Carvytki in patients who have relapsed after just one prior treatment, on the basis of results from the CARTITUDE-4 trial. Here, Carvykti shows even greater benefits over standard care. The best hypothesis as to why has to do with the fitness level of the patients’ T cells. CAR-T therapies are made from the patient’s own T cells, but those cells wear down over years of fighting cancer and enduring multiple rounds of chemotherapy. Used earlier, after just one prior treatment, the harvested T cells are in far better shape, and the therapy built from them is more effective at fighting disease.

Carvykti is currently being evaluated in clinical trials as a first-line treatment, which means that it would be given to newly diagnosed myeloma patients before any other therapy has been tried. If the trial results are positive, this would be a historic game-changer in how patients are treated, with a one-time injection becoming the standard over the arduous procedure of induction regimen, bone marrow transplant and lenalidomide maintenance.

Progression free survival curves show that Carvytki clearly outperforms Abecma. Source: Rodriguez-Otero et al. and San-Miguel et al.

Kochenderfer's lab at the National Cancer Institute first validated BCMA as a target and ran the first-in-human trial. Most of the intellectual groundwork was largely laid in Bethesda, Maryland, in the US. But the therapy that ultimately reached patients and that is now rewriting the prognosis for multiple myeloma did not emerge from that lineage. This was an early sign that China would become an important force in biotechnology.

Made in China

Just last week, in late May 2026, the New York Times ran an article reporting on a clear shift at ASCO, oncology’s most prestigious annual conference. The stage was increasingly dominated by novel therapeutics developed in China. Global pharmaceutical companies are racing to license Chinese-developed drugs, drawn by a combination of lower costs, faster development timelines and a streamlined regulatory environment. The end result of this is a realignment of where the world’s medicines are being discovered. Roughly half of all major drug licensing deals struck so far this year involve drugs originating from China. What is striking is that this share was nearly zero just a decade ago.

The Carvykti case should have been an early warning. Already by 2016, the same year Legend began the clinical trial that would first reveal Carvykti’s potential, China had overtaken the United States in the number of cell-therapy clinical trials. The gap has been growing since.

China’s ongoing biotechnology transformation is the product of deliberate industrial policy. The Made in China 2025 initiative explicitly identified biotechnology and advanced medical technologies as strategic national priorities, and a series of targeted policies followed. Among them was the Thousand Talents Plan, designed to draw overseas Chinese scientists back from Western institutions. BeiGene, Innovent, and Junshi, which are now three of China’s leading oncology biotechs, were all founded or are now led by researchers who had trained in the United States before returning home.

Yet perhaps the most consequential advantage China has built lies in its clinical trial ecosystem. Chinese hospitals make extensive use of investigator-initiated trials. These are early-stage studies that allow oncologists to quickly assess whether a drug shows genuine promise. In China, such a trial can be up and running within roughly six months of a patient consultation with an academic oncologist. In the United States, the same process can take eighteen months or more, bogged down by regulatory preparation that includes a lengthy Investigational New Drug application. This is a document that can run to thousands of pages and is laden with a host of requirements which are unnecessary at such an early stage of development.

The most valuable thing early-stage trials enable is iteration. They allow tight feedback between the clinic and the lab. There are countless ways to engineer a better CAR-T cell, and many cannot be evaluated in the laboratory alone. No cell culture or animal model fully replicates the complexity of a human tumor, and AI is unlikely to close that gap anytime soon. We simply lack the training data to capture what tumors are actually like in vivo: their geometry, vascularization and biomechanical properties.

China’s ability to run these trials quickly and at scale gave it a structural advantage in that learning process, whereas the US is currently undermining itself through burdensome manufacturing requirements and regulatory bureaucracy that make early experimentation slower and more costly than it needs to be. The policy world has, belatedly, taken notice of this. A proposal in the President’s 2027 FDA budget would streamline early-stage trials. This a welcome recognition that regulatory friction on early experimentation is a competitive liability. But a budget proposal is not a policy and will remain aspirational unless Congress acts.

For now, American and European pharmaceutical companies largely retain the upper hand in the later stages of clinical development, as shown by the fact that Legend ultimately licensed Carvytki to a large American biopharmaceutical company to get it approved. But the pipeline that feeds those late-stage trials is increasingly Chinese. Such early-stage dominance turned into vertical integration of the entire chain in solar panels, batteries and electric vehicles, and LCD panels. The question is how long Western companies can sustain their advantage at the later stages, when the discoveries that make those stages possible are increasingly being made elsewhere.

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Ruxandra Teslo is an editor at Works in Progress. Amol Punjabi is chief product officer at OpenEvidence.