CD19 CAR-NK Cell Therapy Achieves 15-Month CR in Rare B-Cell Lymphoma

Treatment with a CD19 CAR-natural killer (NK) cell therapy and rituximab (Rituxan) induced sustained complete responses (CRs) among a small group of patients with Waldenström lymphoma, a rare B-cell lymphoma, in the phase 1 QUILT-106 trial (NCT06334991), according to a news release from the developers, ImmunityBio.¹

Specifically, the CAR-NK cell therapy conferred a CR of 7 months and 15 months, respectively, among 2 evaluable patients who received 8 doses of therapy plus rituximab and no subsequent treatment. Moreover, a disease control rate (DCR) of 100% was observed across 4 patients treated with 8 doses of therapy after experiencing disease progression following standard-of-care treatment. Furthermore, the developers highlighted the rapid onset of CR after 2 cycles and the durability of CR in the absence of subsequent treatment as potential for long-term immune-mediated disease control.

“This updated follow-up reinforces the central thesis that restoring and activating the immune system can deliver durable control of disease without chemotherapy or lymphodepletion,” Patrick Soon‑Shiong, MD, founder, executive chairman, and global chief medical and scientific officer of ImmunityBio, said in the news release.¹ “Seeing [CRs] persist beyond a year after treatment has stopped, in patients who had exhausted available options, represents a meaningful advance for patients with this rare disease of Waldenström lymphoma and validates CAR-NK as a potential next-generation immunotherapy platform.”

Additional findings revealed that 2 patients with extensive disease at baseline observed CRs after 4 doses of the CAR-NK–based combination, including 1 patient with 95% of bone marrow infiltrated with tumor cells and another with multiple lymphomatous bone lesions. In the patient with significant bone marrow involvement, complete bone morphological remission was sustained in addition to the 15-month CR following the fourth dose of therapy.

The developers engineered the targeted high-affinity NK cell therapy as an off-the-shelf treatment designed to express a CD19-specific CAR and a high-affinity CD16 receptor. Intended as a means of facilitating dual anti-tumor mechanisms, the combination of CD19 CAR-NKs with rituximab, an anti-CD20 monoclonal antibody, could target both CD19- and CD20-expressing lymphoma cells to enhance tumor elimination.

The first-in-human, ongoing study enrolled patients with CD19- and CD20-expressing relapsed/refractory B-cell non-Hodgkin lymphoma and assigned the initial 3 to receive the study therapy in a staggered fashion, with a 7-day interval to manage toxicities.² Subsequent patients received one 3-week cycle of the CAR-NK therapy as a single agent, and following a 1-week safety pause, began one 3-week cycle of the treatment in combination with rituximab.

Following first tumor assessment, in the absence of progressive disease, patients could receive up to 2 additional 3-week cycles of the combination regimen.

The coprimary end points of the trial included the safety of the combination as well as the incidence of treatment-emergent and serious adverse effects. The secondary end point was best tumor response per Lymphoma Response to Immunomodulatory Therapy Criteria.

Those eligible for enrollment on the trial included patients 18 years and older who had completed at least 2 prior lines of cytotoxic chemotherapy, received prior rituximab or an anti-CD20 antibody, had measurable disease per Lugano classification within 8 weeks of enrollment, and had CD19- or CD20-positive disease on diagnostic or repeat biopsy specimen. Additional inclusion criteria included having an ECOG performance status of 0 or 1 and expected survival of greater than 16 weeks.

According to the developers, a follow-up study is planned to assess the CAR-NK cell therapy with nogapendekin alfa inbakicept (Anktiva) and rituximab in indolent lymphomas.

“These data highlight a favorable safety and efficacy profile that is particularly important for patients with indolent yet incurable lymphomas,” Lennie Sender, MD, chief medical officer of Liquid Tumors and Cell Therapy at ImmunityBio, expressed in the news release.¹ “To date, all patients have been treated as outpatients with no serious adverse events, demonstrating the feasibility of delivering potent cellular immunotherapy without the morbidity traditionally associated with cell-based treatments.”

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 16, 2026. https://tinyurl.com/4kxyxawv
2. Study for subjects with relapsed/​refractory non-Hodgkin lymphoma. ClincialTrials.gov. Updated January 14, 2025. Accessed January 16, 2026. https://tinyurl.com/2t2d887d