Five years after a single infusion of ciltacabtagene autoleucel (cilta-cel; Carvykti), one in three patients with heavily pretreated multiple myeloma is still alive and progression-free. This result has forced doctors to rethink what is possible for these patients. The idea of a functional cure, once out of reach, is now part of the conversation—if the right patients get the right treatment at the right time.
As of 2026, two BCMA-directed CAR-T therapies—idecabtagene vicleucel (Abecma) and ciltacabtagene autoleucel (Carvykti)—are approved for multiple myeloma, with Carvykti first approved in 2022.
Sidana, who leads the Myeloma CAR T program at Stanford, put it simply: "For the majority of patients, CAR T first makes sense." Hansen, from Moffitt Cancer Center, pointed to the International Myeloma Working Group guidelines and German data showing that making cilta-cel earlier leads to better product quality—healthier T cells and more successful infusions. Mewawalla, at Allegheny Health Network, said the real-world impact is huge: "When CARTITUDE-1 data came out—especially the 1-in-3 patients being progression-free and alive at 5 years in a population that was so heavily pretreated, with no prior treatment anywhere close to that—that is what made us start using the word 'cure' or defining cure in myeloma."
Cilta-cel is now moving into earlier lines of therapy. According to 2026 clinical materials, cilta-cel is considered a second-line option for patients at their first relapse, especially those with relapsed or refractory disease. The latest National Comprehensive Cancer Network (NCCN) guidelines now separate relapse after 1–3 lines of therapy from relapse after more than three lines. This shows a clear trend toward using targeted and T-cell–redirecting treatments earlier. Cilta-cel is also listed as an option for patients who are lenalidomide-refractory and have had at least one prior therapy, which supports its use earlier in the disease.
The U.S. Food and Drug Administration (FDA) continued to expand the therapeutic arsenal for multiple myeloma in 2026, granting accelerated approval to an iberdomide combination on August 13, 2026, underscoring the growing competition in earlier lines of therapy.
Managing expectations is tricky. Two-thirds of patients will not reach five years. Both Mewawalla and Hansen are careful to separate population-level data from what any one patient might expect. Still, the chance for a treatment-free period—sometimes years without chemotherapy—has changed how patients see their disease. Many, after relapse, ask for a second CAR T just for the chance to live without daily reminders of cancer.
Community oncologists are now key to this shift. Mewawalla called for universal referral at diagnosis, using telehealth to cut down on travel and making sure that when advanced therapies are needed, relationships and records are ready. Hansen warned against starting holding therapy before checking trial eligibility and said not to use lymphotoxic drugs or T-cell engagers before apheresis. The main point: community and academic centers must stay in close, real-time contact.
Discharge after day 28 is not the finish line. Mewawalla described a smooth handoff: a short, one-page summary to the community team, monthly telehealth check-ins, and a direct phone line for late toxicities. Hansen laid out a strict follow-up plan—weekly labs, quarterly visits, and a vaccination series starting at month three. Standard care includes acyclovir and Pneumocystis prophylaxis, with IVIG arranged locally for up to a year.
Delayed toxicities are now a major concern. Hansen pointed to two: movement neurocognitive syndromes (like Parkinsonism) and immune effector cell–associated enterocolitis (IEC-E). Both can show up weeks or months after infusion, sometimes in the same patient. Early signs—flat facial expression, shuffling walk, or subtle mood changes—should prompt quick action. Dexamethasone is used for those at risk. IEC-E, which often looks like non-bloody diarrhea, needs endoscopic confirmation and is now treated with JAK inhibitors or T cell-directed therapies, not anti-TNF drugs. Because these toxicities can overlap, both academic and community teams need to stay alert.
These challenges are not unique to myeloma. Similar issues have come up in other CAR T uses, like the reported earlier efforts to expand CAR T to solid tumors by exposing hidden cancer markers. The takeaway: science is moving fast, but who benefits will depend on how well teams coordinate and follow the evidence on sequencing.
As CAR T moves up in the myeloma treatment plan, the success rate from apheresis to infusion is now close to 100%. This is thanks to lower disease burden and better bridging strategies. The shared-care model—built on clear discharge notes, telehealth, and direct communication—now anchors safe, effective CAR T delivery. For the field, the message is clear: late-line, last-ditch CAR T is over. The future belongs to those who can deliver these therapies earlier, more safely, and in real partnership with the community. Anything less risks missing the chance for a functional cure.
