Dr Porter on Community-Based CAR T-Cell Therapy Administration for R/R CLL

David L. Porter, MD, director, Cell Therapy and Transplant, Jodi Fisher Horowitz Professor in Leukemia Care Excellence, Perelman School of Medicine, Penn Medicine, discusses the utility of 

CAR T-cell therapy in the community setting

 for patients with relapsed/refractory chronic lymphocytic leukemia (CLL).

Community oncologists and patients must understand the role of CAR T-cell therapy in CLL management, as well as the toxicities associated with these products, Porter begins. However, most importantly, community oncologists need to refer patients to specialized centers with expertise in administering this treatment, Porter emphasizes. Accessibility limitations exist; more patients could benefit from CAR T-cell therapy than those who are currently referred, often due to a lack of comprehensive information, he says. Patients with relapsed or refractory disease should be directed to centers proficient in administering CAR T-cell therapies to at least receive an expert opinion, Porter explains.

Addressing barriers and improving accessibility to CAR T-cell therapy can also be achieved by extending the administration of this therapy into community settings rather than centralizing it solely in major academic centers, he continues. Clinical trial investigators and treating oncologists should continue to collaborate with partners and affiliates to administer CAR T-cell therapy in more community hospitals, Porter states. Although not every oncology practice in the United States will be able to provide CAR T-cell therapy, select community hospitals, even those not directly linked to major academic centers, can develop the necessary expertise to offer this treatment locally, he elucidates.

This initiative has the potential to significantly improve access to CAR T-cell therapy for patients who live far from major academic centers or urban areas, Porter expands. Developing CAR T-cell expertise in community settings will ensure that more patients receive timely and effective treatment, he says. Porter encourages community practices to view this as a collaborative effort, working together with academic institutions to ensure timely referrals and explore ways to disseminate CAR T-cell therapy beyond academic centers. By partnering with community oncologists, academic institutions aim to expand access to this innovative therapy and improve patient outcomes across a broader geographic area, he concludes.

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David L. Porter, MD, discusses the utility of CAR T-cell therapy in the community setting for relapsed/refractory chronic lymphocytic leukemia.

Dr Porter on the Future of CAR T-Cell Therapy in Relapsed/Refractory CLL

David L. Porter, MD, director, Cell Therapy and Transplant, Jodi Fisher Horowitz Professor in Leukemia Care Excellence, Perelman School of Medicine, Penn Medicine, discusses 

 in patients with relapsed/refractory chronic lymphocytic leukemia (CLL).

CAR T-cell therapy in CLL holds promising potential, especially when considering innovative combinations with existing treatments such as ibrutinib (Imbruvica), Porter begins. In a phase 1 clinical trial (NCT02640209), patients previously treated with ibrutinib who did not achieve complete remission (CR), were administered CAR T-cell therapy, he says. The outcomes were remarkably encouraging, with 44% (95% CI, 23%-67%) of patients attaining CR within 3 months, Porter explains. Notably, advanced testing revealed undetectable levels of minimal residual disease in most patients, hinting at a broader scope of CAR T-cell therapy benefit beyond conventional CR measurements, according to Porter. Furthermore, many patients sustained these responses over the long term, indicating the therapy’s enduring efficacy, he elucidates.

The prospect of refining therapies to enhance patient outcomes fuels considerable excitement, Porter continues. Although CAR T-cell therapy has profound efficacy in responsive patients, efforts are underway to extend its benefits to a broader patient population, he explains. Various strategies are being explored, including the use of novel CAR constructs fortified with additional cytokines to amplify CAR T-cell activity, Porter reports. Additionally, studies investigating combination therapies, such as pairing CAR T cells with BTK inhibitors or employing innovative approaches to select more potent CAR T cells, are underway, Porter notes.

Innovations such as allogeneic CAR T-cell therapy and the exploration of alternative CAR-modified cell types, such as natural killer cells, present additional avenues for CLL management, he expands. These approaches offer unique advantages and are poised to contribute significantly to the evolution of cell-based therapies, Porter says. Advancements in CLL-specific CAR T-cell research hold implications beyond this specific disease, shaping the broader trajectory of CAR T-cell therapy development, he states. With rapid progress characterizing the field, the future of CAR T-cell therapy appears increasingly promising, continually advancing toward more effective and accessible treatment modalities, Porter concludes.

David L. Porter, MD, discusses the future of CAR T-cell therapy in patients with relapsed/refractory chronic lymphocytic leukemia.

David L. Porter, MD, discusses knowledge gaps regarding the optimal use of CAR T-cell therapy in relapsed/refractory chronic lymphocytic leukemia.  

 Dr Porter on Understanding Gaps in CAR T-Cell Therapy for R/R CLL

David L. Porter, MD, director, Cell Therapy and Transplant, Jodi Fisher Horowitz Professor in Leukemia Care Excellence, Penn Medicine, discusses knowledge gaps regarding the optimal use of CAR T-cell therapy for patients with relapsed/refractory chronic lymphocytic leukemia (CLL), as presented at the Vanderbilt Stem Cell Transplant and Cellular Therapy Symposium.

CAR T-cell therapies have shown high responses in relapsed/refractory CLL, with some patients remaining in remission for nearly 14 years, Porter begins. Despite the efficacy of this drug class, limited patients will experience this benefit, he notes. For instance, the phase 1/2 TRANSCEND CLL 004 trial (NCT03331198) demonstrated high responses with the CAR T-cell therapy lisocabtagene autoleucel (liso-cel; Breyanzi) in pretreated patients for whom no other treatment is effective, supporting the 

FDA's decision to grant accelerated approval to liso-cel

 in pretreated relapsed/refractory CLL or SLL in March 2024. However, the complete response rate achieved with liso-cel in the overall population (n = 65) was only 20% (95% CI, 11.1%-31.8%), Porter details.

Improving these response rates is crucial, Porter continues. One promising approach involves combination therapies, such as administering CAR T-cells alongside ibrutinib (Imbruvica) or other BTK inhibitors. These combinations may enhance response rates and durability, he explains. Additionally, long-term follow-up is essential to monitor these patients effectively. Given that CLL is a chronic disease, late relapses are possible, although the likelihood is low among patients with advanced multiple-relapsed disease, Porter adds.

Another critical aspect is addressing the recent concerns about secondary primary malignancies and T-cell lymphomas associated with CAR T-cell therapies, Porter says. The FDA has updated the boxed warnings for all approved CAR T-cell therapies to include the serious risk of T-cell malignancies, highlighting the need for ongoing long-term follow-up. This vigilance is necessary not only for patients with CLL, but for all patients receiving CAR T-cell therapies. These efforts will help address the serious risks and optimize the long-term benefits of CAR T-cell therapies for CLL and other hematologic malignancies, he concludes.

David L. Porter, MD, discusses knowledge gaps regarding the optimal use of CAR T-cell therapy in relapsed/refractory chronic lymphocytic leukemia.
 

Dr Porter on Understanding Gaps in CAR T-Cell Therapy for R/R CLL

Dr Porter on the Efficacy of CAR T-Cell Therapy in Relapsed/Refractory CLL

David L. Porter, MD, director, Cell Therapy and Transplant, Jodi Fisher Horowitz Professor in Leukemia Care Excellence, Penn Medicine, discusses data supporting the use of CAR T-cell therapy alone or in combination regimens for patients with relapsed/refractory chronic lymphocytic leukemia (CLL), as presented at the Vanderbilt Stem Cell Transplant and Cellular Therapy Symposium.

Considerable data have emerged regarding the use of CAR T-cell therapy in the treatment of patients with relapsed/refractory CLL, highlighting the transformative potential of this treatment modality, Porter says. Notably, conventional CLL treatments have elicited suboptimal outcomes in this patient population, underscoring the need for novel therapeutic approaches, Porter emphasizes. Clinical trials with CAR T-cell therapy over the last decade have yielded pivotal findings, including overall response rates (ORRs) and complete response (CR) rates ranging from approximately 30% to 60%, Porter notes. Although CAR T-cell therapy is not universally effective, these products often produce sustained CRs for patients with CLL. This is particularly impressive considering the limited treatment alternatives available for this patient population, Porter explains. The data accrued with CAR T-cell therapy in CLL strongly indicate that many patients achieving a CR with these products may also achieve long-term disease eradication, representing potential cures, according to Porter.

Additional studies in patients with CLL have explored the combination of CAR T-cell therapy and BTK inhibitors, such as ibrutinib (Imbruvica). Data from these trials, including those conducted at Penn Medicine, have shown enhanced ORRs and a substantial likelihood of achieving minimal residual disease negativity following sequential treatment with ibrutinib and CAR T-cell therapy, further reinforcing interest in this combination regimen, Porter says. Although treatment outcomes with CAR T-cell therapy alone in relapsed/refractory CLL are promising, ongoing research suggests that greater efficacy can be achieved with these products through the integration of novel therapeutic modalities, Porter concludes.

David L. Porter, MD, discusses the use of CAR T-cell therapy alone or in combination regimens in relapsed/refractory chronic lymphocytic leukemia.

David L. Porter, MD

Articles

Dr Porter on Community-Based CAR T-Cell Therapy Administration for R/R CLL

Dr Porter on the Future of CAR T-Cell Therapy in Relapsed/Refractory CLL

Dr Porter on Understanding Gaps in CAR T-Cell Therapy for R/R CLL

Dr Porter on the Efficacy of CAR T-Cell Therapy in Relapsed/Refractory CLL