Is Johnson & Johnson’s CARVYKTI shifting the multiple myeloma treatment curve?

Johnson & Johnson (NYSE: JNJ) has unveiled new long-term data from the Phase 3 CARTITUDE-4 trial that could reshape how oncologists and payers think about the role of CAR-T therapy in relapsed or refractory multiple myeloma. At the 2025 American Society of Hematology (ASH) Annual Meeting in Orlando, Florida, the American healthcare major presented data showing that 80.5 percent of standard-risk patients treated with CARVYKTI (ciltacabtagene autoleucel; cilta-cel) remained progression-free and treatment-free 30 months after a single infusion. These results come from patients receiving CARVYKTI as early as second-line therapy, rather than the late-line salvage setting where most CAR-T treatments have traditionally been used.

The updated data offers one of the clearest signs yet that earlier-line use of CAR-T therapy may unlock more durable remissions by leveraging stronger immune fitness. The median follow-up of 33.6 months in the trial’s as-treated cohort showed a plateau in disease progression, raising hopes that some patients could experience a functional cure.

With more than 9,000 patients now treated globally in both trial and real-world settings, Johnson & Johnson is positioning CARVYKTI as a treatment capable of shifting the paradigm in multiple myeloma—particularly for standard-risk patients after first relapse.

How is CARVYKTI performing in the second-line setting versus standard care?

CARTITUDE-4 is the first randomized Phase 3 trial evaluating the efficacy and safety of CARVYKTI in patients with relapsed multiple myeloma who are refractory to lenalidomide. The study compared CARVYKTI with standard of care regimens, including PVd (pomalidomide, bortezomib, dexamethasone) and DPd (daratumumab, pomalidomide, dexamethasone), in patients who had received one to three prior lines of therapy.

Among the 176 patients who received CARVYKTI in the as-treated arm of the study, 59 had standard-risk cytogenetics. These patients achieved a 30-month progression-free survival rate of 80.5 percent following a single infusion. Notably, every one of the 26 patients in this subgroup who achieved minimal residual disease-negative complete response at 12 months remained progression-free at the 30-month mark. This data set provides one of the strongest arguments to date for moving CAR-T treatment into earlier lines, where immune resilience may enhance therapeutic durability.

Johnson & Johnson emphasized that CARVYKTI is currently the only CAR-T therapy to have demonstrated a statistically significant overall survival benefit compared to standard regimens in this patient population.

What role does immune fitness play in the long-term durability of CARVYKTI?

Beyond the clinical endpoints, Johnson & Johnson also presented new translational analyses that highlight why earlier-line use of CARVYKTI may produce superior outcomes. These analyses, drawn from both CARTITUDE-1 and CARTITUDE-4 data, show that patients treated after one or two prior therapies exhibit stronger immune fitness, including higher levels of CD4⁺ naïve T cells in peripheral blood.

The presence of these immune markers is believed to correlate with improved T-cell expansion and persistence after CARVYKTI infusion. In contrast, patients who receive the therapy after three or more prior lines tend to have more exhausted immune profiles. These differences were also evident in bone marrow samples, where patients treated after just one prior line had a more immune-activated tumor microenvironment compared to those treated later.

By linking these biomarkers with observed progression-free survival outcomes, the data suggests that immunologic health may be a key predictor of CAR-T efficacy. This reinforces the rationale for administering CARVYKTI earlier in the treatment sequence, while patients still possess relatively intact immune systems.

What are the implications for real-world usage of CARVYKTI?

Johnson & Johnson has treated more than 9,000 patients with CARVYKTI across both clinical trials and real-world settings, offering a broad base of evidence for the therapy’s safety and efficacy. As the product moves beyond tertiary academic centers into community oncology practices, the company is placing emphasis on building operational experience, data repositories, and safety protocols that support its use earlier in the treatment pathway.

Jordan Schecter, M.D., Vice President of Research and Development in Multiple Myeloma at Johnson & Johnson Innovative Medicine, said the company’s goal is to treat patients as early as possible, when they have the highest chance of achieving durable remission. He added that CARVYKTI is the first and only CAR-T to show overall survival benefit against standard of care in this space.

Luciano Costa, M.D., Ph.D., Professor of Medicine at the University of Alabama and principal investigator of the CARTITUDE-4 study, noted that treating patients at first relapse could lead to deeper, longer-lasting responses. Both executives emphasized that the results point toward the possibility of achieving long-term remission or even functional cure in select patient subgroups.

How does CARVYKTI differ mechanistically from other multiple myeloma therapies?

CARVYKTI is a B-cell maturation antigen (BCMA)-targeted, genetically modified autologous T-cell therapy. It works by harvesting a patient’s own T cells and reprogramming them to express a chimeric antigen receptor that binds specifically to BCMA, a protein commonly found on the surface of malignant plasma cells.

The CARVYKTI construct features two BCMA-binding domains, enhancing its avidity and targeting precision. Upon infusion, the modified T cells recognize BCMA-positive cancer cells, activate, proliferate, and destroy the target cells. This approach offers a fundamentally different mechanism compared to proteasome inhibitors or immunomodulatory drugs, which act more broadly and require continuous administration.

The therapy received its first U.S. Food and Drug Administration approval in February 2022 for use in adult patients with RRMM who had received four or more prior therapies. In April 2024, it became the first and only CAR-T therapy in the U.S. approved for use after just one prior line of treatment, provided the patient is refractory to lenalidomide. The European Medicines Agency approved a similar label expansion shortly thereafter.

What do earlier trials like CARTITUDE-1 contribute to the CARVYKTI case?

While CARTITUDE-4 focuses on earlier-line use, the earlier CARTITUDE-1 study laid the foundation for CARVYKTI’s approval in late-line settings. That open-label Phase 1b/2 trial enrolled heavily pretreated patients, 99 percent of whom were refractory to their most recent therapy. Importantly, 88 percent of participants were triple-class refractory, meaning they had failed all three major drug classes used in multiple myeloma treatment.

Despite these challenges, CARVYKTI showed a median progression-free survival significantly longer than the expected sub-six-month benchmark for this population. The safety profile observed in CARTITUDE-1 also informed outpatient dosing protocols that are now being tested in follow-up trials.

Together, CARTITUDE-1 and CARTITUDE-4 help build a compelling longitudinal case for CARVYKTI across multiple treatment lines, patient profiles, and healthcare settings.

How does this impact the broader outlook for multiple myeloma care in 2026?

Multiple myeloma remains the third most common blood cancer globally and is still considered incurable. In 2024, more than 35,000 new cases were expected in the United States alone, with over 12,000 deaths projected. The five-year survival rate stands at approximately 59.8 percent, and patients typically cycle through multiple lines of therapy over the course of their disease.

Given the chronic and relapsing nature of multiple myeloma, a one-time treatment that offers multi-year remission without ongoing maintenance represents a significant step forward. CARVYKTI’s long-term data now positions it as a front-runner among cell therapies seeking to occupy earlier positions in the treatment sequence. If future updates continue to confirm durability and manageable safety in broader patient populations, it may push payers and clinical guidelines to rethink sequencing logic.

Additionally, biomarker-driven selection based on immune fitness could become a new layer of personalization in how cell therapies are deployed, particularly in standard-risk cytogenetic populations.

What is the institutional sentiment and investor outlook for Johnson & Johnson?

Shares of Johnson & Johnson (NYSE: JNJ) remained stable following the ASH 2025 presentation, reflecting cautious optimism from institutional investors. Analysts tracking the oncology pipeline believe the new CARTITUDE-4 data strengthens the company’s cell therapy franchise and enhances its oncology competitiveness, particularly in the hematologic malignancy segment.

Market observers expect increased engagement with payers on value-based pricing models for CARVYKTI, especially as its use moves into earlier lines where competing regimens are often less costly. However, manufacturing capacity and logistics will remain critical in determining scalability and profitability.

General sentiment from institutional desks is constructive, with a hold-to-buy bias depending on risk appetite, reimbursement assumptions, and upcoming regulatory updates. The oncology division is viewed as a strategic asset within Johnson & Johnson’s broader pharmaceutical portfolio, especially as other pipeline candidates approach late-stage milestones in 2026.

What are the key takeaways from Johnson & Johnson’s CARTITUDE-4 CARVYKTI data update?

• 80.5 percent of standard-risk patients remained progression-free and treatment-free at 30 months after a single infusion of CARVYKTI in the second-line setting, according to new Phase 3 CARTITUDE-4 trial data.

• All 26 patients who achieved minimal residual disease-negative complete response at 12 months remained progression-free at the 2.5-year mark, highlighting the potential for deep and durable remission.

• Immune biomarker analysis showed that patients treated earlier had stronger immune fitness, including higher CD4⁺ naïve T cells and more immune-activated bone marrow profiles, which correlated with longer progression-free survival.

• Johnson & Johnson emphasized CARVYKTI as the first and only CAR-T therapy to demonstrate overall survival benefit in a head-to-head comparison with standard-of-care regimens like PVd and DPd.

• The company has now treated over 9,000 patients globally with CARVYKTI, offering substantial clinical and real-world data to support broader use beyond academic centers.

• CARTITUDE-4 findings support moving CARVYKTI earlier in the treatment sequence, particularly in standard-risk patients after first relapse, where immune systems are more intact.

• Label expansions in the U.S. and Europe in 2024 have already enabled use after just one prior therapy, significantly expanding the eligible patient population.

• CARTITUDE-1 continues to validate CARVYKTI’s efficacy in late-line, triple-class refractory patients, forming the foundation for ongoing outpatient studies and safety monitoring.

• Institutional sentiment toward Johnson & Johnson’s oncology franchise remains cautiously optimistic, with analysts tracking cell therapy manufacturing scalability, value-based pricing, and regulatory outcomes.

• CARVYKTI’s positioning in 2026 could trigger a broader reassessment of multiple myeloma treatment sequencing, potentially displacing older regimens in earlier treatment lines.