CD19 CAR-NK Cell Therapy Yields Complete Responses in Waldenstrom NHL

Early results from the ongoing QUILT-106 clinical trial (NCT06334991) show that the treatment combination of CD19 chimeric antigen receptor natural killer (CAR-NK) cells with rituximab (Rituxan) can yield complete responses (CR) and disease control in patients with Waldenstrom non-Hodgkins lymphoma (NHL).^1,2

The updated results from the QUILT-106 study demonstrate both rapid and durable responses in a heavily pretreated patient population.

To date,100% disease control has been observed in the first 4 patients enrolled. Two patients evaluable for long-term follow-up have demonstrated sustained and ongoing complete remissions at 7 and 15 months, respectively, after receiving their final dose. CRs were observed after only 2 cycles (4 doses of CAR-NK plus rituximab).

Two patients with extensive baseline disease showed remarkable outcomes:

1. Multiple Bone Tumors: A patient presenting with multiple lymphomatous bone lesions achieved a CR that is ongoing for 7 months to date.
2. Extensive Bone Marrow Infiltration: A patient whose bone marrow was approximately 95% replaced by tumor cells achieved a complete bone morphological remission after 4 doses. This CR has been maintained for 15 months and remains ongoing without any further treatment.

Study Overview and Methodology

The QUILT-106 clinical study is an ongoing trial evaluating an allogeneic CD19 CAR-NK cell therapy for patients with Waldenstrom NHL, a rare B-cell malignancy. The study focuses on patients who have previously failed standard treatments, addressing a significant unmet medical need.

The treatment combines CD19 CAR-NK cells with rituximab, an anti-CD20 monoclonal antibody. This dual-targeting approach addresses both CD19 and CD20 markers on lymphoma cells.

The therapy is administered entirely in an outpatient setting. The regimen does not require lymphodepletion, a process that typically involves cytotoxic chemotherapy. Patients receive a total of 4 cycles, with each cycle lasting 21 days. Each cycle consists of 2 doses of CD19 CAR-NK cells and doses of rituximab. Over the full course, patients receive 8 doses of CAR-NK cells and 6 doses of rituximab. After the initial 4 cycles, no further therapy is administered. The response to therapy is evaluated after the first 2 cycles.

Therapeutic Advantages and Patient Benefits

The approach employed in the QUILT-106 study represents a significant departure from conventional CAR-T therapies, offering a more favorable safety profile and greater accessibility.

The entire treatment course is delivered in an outpatient setting, avoiding the need for inpatient hospitalization. No serious adverse events (AEs) have been reported among the treated patients. By being chemotherapy-free and lymphodepletion-free, the regimen avoids the cytotoxic conditioning and associated morbidity traditionally linked to cell-based treatments.

The use of an allogeneic NK cell line means the therapy is "off-the-shelf," potentially simplifying logistics and reducing wait times compared to autologous therapies.

“These data highlight a favorable safety and efficacy profile that is particularly important for patients with indolent yet incurable lymphomas,” said Lennie Sender, MD, chief medical officer at ImmunityBio, in a news release. “To date, all patients have been treated as outpatients with no serious [AEs], demonstrating the feasibility of delivering potent cellular immunotherapy without the morbidity traditionally associated with cell-based treatments.”

Future Directions

Enrollment and follow-up in the QUILT-106 study are ongoing. ImmunityBio plans to build on these successful results with a follow-up study. Additional clinical updates will be provided as more patients become evaluable and the response durability matures.

A new study is being designed to test a 3-part combination of CD19 CAR-NK cells, rituximab, and nogapendekin alfa inbakicept (Anktiva).

REFERENCES

1.ImmunityBio announces durable complete response of 15 months with a chemotherapy-free CD19 CAR-NK cell therapy in Waldenstrom lymphoma. News release. ImmunityBio. January 16, 2026. Accessed January 19, 2026. https://tinyurl.com/3fb87k55

2.Study for subjects with relapsed/refractory non-Hodgkin lymphoma. ClinicalTrials.gov. Updated January 14, 2025. Accessed January 19, 2026. https://clinicaltrials.gov/study/NCT06334991