The blood cancer that became solvable - Works in Progress Magazine

Multiple myeloma is brutal. We may finally have a cure, but American regulatory inertia means that it was discovered abroad.

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.<br>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.

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Multiple myeloma can damage bone, especially the vertebrae in the spine, leading to severe pain and impaired mobility.

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.<br>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.<br>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.<br>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.<br>The brutality of myeloma treatment<br>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.<br>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...