Brad Rovin, MD

The Future of CAR-T in Lupus Nephritis Treatment, With Brad Rovin, MD

The emergence of CAR-T cell therapy in lupus nephritis has generated significant excitement, but questions remain around how and when this intensive approach should be used. While early studies have focused on patients with refractory disease, the broader clinical vision may extend much earlier in the disease course, particularly as safety and feasibility continue to improve.

 at at the World Congress of Nephrology (WCN) Conference in Yokohama, Japan, Brad Rovin, MD, said the current emphasis on refractory populations reflects regulatory caution, ensuring that higher-risk therapies are first tested in patients with limited alternatives. However, he suggests this approach may not fully capture the therapy’s potential.

Check out part 1 of the interview with Rovin 

Patients with longstanding, treatment-resistant disease often have accumulated, irreversible damage, which may limit the likelihood of achieving full recovery. In contrast, he envisions a future where CAR-T therapy could be used earlier, potentially at the time of diagnosis, to alter the disease trajectory before significant organ damage occurs.

He emphasizes that this shift could be particularly meaningful for the predominantly young patient population affected by lupus nephritis, as conventional treatment regimens often involve prolonged immunosuppression, multiple medications, and significant side effects, all of which can disrupt education, careers, and family planning. If CAR-T therapy can be delivered safely and efficiently, it may offer the possibility of durable remission with reduced long-term treatment burden.

Despite this promise, Rovin notes that logistical barriers remain. Current autologous CAR-T approaches require harvesting and engineering a patient’s own cells, a process that can take weeks and may necessitate holding background immunosuppression. This delay, along with the need for hospitalization, complicates real-world implementation. Looking ahead, he highlights the potential of allogeneic, “off-the-shelf” CAR-T products designed to evade immune rejection, which could streamline delivery and enable outpatient administration.

He also points to emerging alternatives, such as bispecific antibodies that engage T cells without requiring cell harvesting. While these agents may offer greater convenience, they still carry risks such as cytokine release syndrome and require careful evaluation.

Ultimately, he underscores that the future of CAR-T therapy will depend on advances in precision medicine. Identifying which patients are most likely to benefit and aligning treatment strategies with patient preferences will be critical. As the evidence base rapidly expands, he stresses the importance of shared decision-making and continued clinical investigation to define the optimal role of these therapies in lupus care.

Relevant disclosures for Rovin include Biogen, GSK, Genentech/Roche, BMS, Travere, Alexion, Novartis, AstraZeneca, Otsuka, Calliditis, and others.

 Allogeneic anti-CD19 CAR-T cells induce remission in refractory systemic lupus erythematosus. 

https://doi.org/10.1038/s41422-025-01128-1

Hsieh EWY, Chung JB, Amin A, et al. Key considerations for advancing chimeric antigen receptor (CAR) T-cell therapy for systemic lupus erythematosus (SLE): a multi-partner/disciplinary working group perspective. 

https://doi.org/10.1136/rmdopen-2025-005866

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CAR-T therapy in lupus may shift earlier in care, but challenges in access, logistics, and patient selection remain as the field moves toward precision treatment.

Can CAR-T Cell Therapy Transform Lupus Nephritis Care? With Brad Rovin, MD

The treatment of lupus nephritis has long been challenged by profound disease heterogeneity and incomplete responses to standard immunosuppressive therapies. Despite recent advances and newly approved agents, many patients still fail to achieve complete remission. Against this backdrop, the emergence of CAR-T cell therapy represents a potentially transformative step, rooted in the field’s broader shift toward precision medicine and deeper immune modulation.

 at the World Congress of Nephrology (WCN) Conference in Yokohama, Japan, Brad Rovin, MD, explains how the field has historically relied on broadly acting immunosuppressive approaches, such as high-dose cyclophosphamide or mycophenolate, which “treat everything” but fail to account for the biological variability across patients. He says that this one-size-fits-all strategy is increasingly being replaced by efforts to tailor therapy more precisely, particularly as it has become clear that more than half of patients do not achieve complete clinical remission with existing options.

“I think with the idea of using something like a CAR-T cell, we borrow a lot of things from oncology, there's no question about it,” he said. “The idea was, could we affect the immune system in a way that renders it less likely to attack in an autoimmune way for some prolonged period of time? I'm hesitant to use the word cure, because I don't know that we've established cure yet. I think the CAR-T data show that we can, in some patients, achieve a prolonged drug free response. Whether that is a cure in some people, we'll see.”

A key differentiator, Rovin explains, lies in the depth and breadth of B-cell targeting. Unlike conventional anti-CD20 therapies like obinutuzumab (Gazyva), which target a narrower subset of B cells, CAR-T therapies directed at CD19 affect a broader range of the B-cell lineage, including antibody-producing populations. He highlights that CAR-T therapy also appears to induce more complete depletion within lymphoid tissues, including germinal centers, which may be critical for sustained disease control and may go beyond what is achieved with current therapies.

He describes the most striking findings to date as reports of sustained clinical remission lasting up to 4 years without ongoing immunosuppression. However, he emphasizes that these results are not universal, and the therapy carries significant risks, including profound immunosuppression and potential toxicities.

Looking ahead, Rovin stresses the importance of careful patient selection, transparent communication, and continued clinical investigation. While CAR-T therapy may represent a paradigm shift in lupus care, defining its long-term role and balancing its promise with its risks will be essential as the field moves forward.

“I think now it's up to us to continue the investigations, which are ongoing, and now trials are enrolling pretty well and and try to sort these issues out, but like any new therapy, there's going to be bumps, and I think that this is important to think about when we talk to our patients and families about this,” he said.

Editors’ Note: Relevant disclosures for Rovin include Biogen, GSK, Genentech/Roche, BMS, Travere, Alexion, Novartis, AstraZeneca, Otsuka, Calliditis, and others.

Brooks A. FDA Approves Obinutuzumab (Gazyva) for Lupus Nephritis. RheumatologyLive. October 20, 2025. Accessed March 29, 2026. 

https://www.rheum-live.com/view/fda-approves-obinutuzumab-gazyva-for-lupus-nephritis

Musa R, Rout P, Qurie A. Lupus Nephritis. StatPearls. January 16, 2025. Accessed March 29, 2026. 

https://www.ncbi.nlm.nih.gov/books/NBK499817/

CAR-T therapy shows potential for deep, durable remission in lupus nephritis, but questions remain on safety, durability, and patient selection.

future of IgAN treatment, highlighting the BlyS/APRIL axis.

The Future of IgA Nephropathy Treatment

This is a video synopsis/summary of a panel discussion involving Jonathan Barratt, PhD, FRCP, and Brad Rovin, MD.

In this discussion, Jonathan Barratt, PhD, FRCP, and Brad Rovin, MD anticipate the imminent release of phase three data for drugs targeting the BAFF (B-cell activating factor) and APRIL (A proliferation-inducing ligand) axis, particularly April only and April and BAFF approaches. They foresee the potential availability of these drugs on the market within the next 24 months if they prove effective and gain approval.

The conversation shifts to safety concerns, emphasizing the favorable risk profile regarding hypogammaglobulinemia and infections associated with BAFF and APRIL inhibitors. Notably, the discussion touches on the crucial issue of vaccine responsiveness, highlighting preliminary data suggesting a less pronounced negative impact on vaccine responses compared to CD20-depleting therapies, especially relevant during the COVID-19 pandemic.

Dr Barratt concludes by urging viewers to keep a close eye on developments in the BAFF/APRIL axis, predicting its integration into the daily practice of healthcare professionals specializing in kidney diseases. He highlights the excitement surrounding established drugs like sibeprenlimab and atacicept, as well as promising newcomers like povetacicept, encouraging viewers to stay informed about forthcoming clinical data in this rapidly evolving field.

Video synopsis is AI-generated and reviewed by HCPLive editorial staff.

Jonathan Barratt, PhD, FRCP, and Brad Rovin, MD, discuss the future of IgAN treatment, highlighting the BlyS/APRIL axis.

clinical trial data regarding the use of povetacicept for the treatment of IgAN.

Use of Povetacicept in Treatment of IgA Nephropathy

Jonathan Barratt, PhD, FRCP, and Brad Rovin, MD, discuss the latest data on drugs targeting the B-cell activating factor (BAFF) and A proliferation-inducing ligand (APRIL) axis in IgA nephropathy (IgAN), presented at the American Society of Nephrology (ASN) meeting. The conversation highlights the growing interest and excitement in the nephrology community about these emerging therapies.

Dr Barratt mentions recent data on sibeprenlimab and povetacicept and emphasizes the significant attention these drugs received at the ASN meeting. He specifically discusses the promising results from sibeprenlimab, showcasing consistent and effective APRIL inhibition, resulting in a reduction in galactose-deficient IgA1 (Gd-IgA1) and translation to reduced proteinuria.

Dr Rovin provides insights into the presentation of data on povetacicept, emphasizing its impressive proteinuria reduction, even at what is referred to as a "low dose." Both experts acknowledge the need for further dose-ranging studies to determine optimal dosing.

The discussion extends to the potential applications of these drugs beyond IgAN. Dr Barratt highlights a patient with membranous nephropathy treated with povetacicept, showing a significant reduction in anti-PLA2R titers, suggesting a potential broader impact on autoantibody-mediated diseases.

The experts discuss the ability of these drugs to target different cell populations, providing a unique advantage in diseases where both pathogenic antibodies and autoantibodies play a role. Dr Barratt emphasizes the potential benefits in lupus, envisioning combined approaches with BAFF and APRIL inhibition.

Dr Rovin concludes by expressing excitement about the multifaceted applications of these drugs in various diseases and suggests rethinking the use of immunosuppression, aiming for effective treatment with reduced overt immunosuppression. The conversation underscores the transformative potential of BAFF and APRIL inhibitors in reshaping the landscape of nephrology therapeutics across multiple diseases.

Drs Jonathan Barratt and Brad Rovin comment on clinical trial data regarding the use of povetacicept for the treatment of IgAN.

Brad Rovin, MD

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