CAR NK

An early look at a study of a chemotherapy-free immunotherapy for patients Waldenström macroglobulinemia (WM), a type of non-Hodgkin lymphoma (NHL), offered encouraging data, according to results released Wednesday by ImmunityBio.¹

QUILT-106 (NCT06334991) is a first-in-human trial evaluating the safety and preliminary efficacy of CD19 chimeric antigen receptor (CAR) natural killer (NK) cell therapy alone and in combination with rituximab, among patients with relapsed or refractory (R/R) CD19⁺CD20⁺ B-cell NHL.² Some patients in the study have WM, which is considered incurable with existing treatment options, making the hunt for novel therapies for these patients a high priority.

What’s more, this treatment is an allogeneic NK cell line, an “off-the-shelf” treatment that expresses a CD19-targeting CAR and a high-affinity CD16 (FcγRIIIa 158V) receptor. Combining CD19 CAR NK cells with anti-CD20 rituximab “could enhance tumor killing,” according to ImmunityBio.

While treatment of different NHL subtypes with personalized CAR T-cell therapy has dramatically shifted the survival prospects for patients with aggressive diseases such as diffuse large B-cell lymphoma, the challenges associated with manufacturing and delivering a treatment for single patients remain. Some patients simply cannot wait several weeks for treatment, so work continues on bispecifics and allogeneic CAR options in multiple blood cancers.

An advantage of CAR NK treatments is that they are powerful and can be combined with other therapies, according to authors of June 2025 paper in Molecular Therapy,³ and this proved the case with the ImmunityBio patients.

ImmunityBio reported that the first 2 evaluable patients with WM, both heavily pretreated, tolerated the new regimen without experiencing significant toxicities. One patient achieved a complete response (CR) with CD19 CAR NK monotherapy, while the second patient achieved CR with CD19 CAR NK in combination with rituximab. Remission was maintained and has been ongoing for 6 months.¹

Of note, infusions were administered in an outpatient setting. ImmunityBio officials said in their statement that study is the first to show the demonstration CRs with chemotherapy-free immunotherapy in late-stage WM patients, thus showing the potential of NK cells.

South African physician and researcher Glenda Gray, MBBCh, DSc, has enrolled 13 patients with NHL at 3 sites in that country, including 3 with WM. To be eligible, participants must express CD19 and CD20 and have active disease after at least 2 lines of chemotherapy-based treatment. All patients receive a lead-in cycle of CD19 CAR NK cell monotherapy, followed by a week of observation for safety reasons. Then, they receive a second cycle of CD19 CAR-NK with rituximab.

Key end points include safety and tolerability and objective response rate (ORR), using standard criteria, according to ImmunityBio.

“The preliminary findings we have submitted for presentation at the American Society of Hematology annual meeting provides the first evidence that novel immunotherapy combinations without chemotherapy lymphodepletion can provide deep and durable remissions in WM even after multiple prior treatments,” lead author Jackie Thomson, MBChB, MMEd, of the Wits University Donald Gordan Medical Center in Johannesburg, South Africa, said in the statement.¹ “Recruitment in this rare subset of lymphoma is ongoing to confirm these findings and to establish this chemo-free strategy as a viable treatment option for relapsed WM.”

Reference

1. ImmunityBio reports complete responses in non Hodgkin Waldenstrom lymphoma patients with chemotherapy free first-in-class CD19 CAR NK immunotherapy. ImmunityBio. August 13, 2025. Accessed August 13, 2025. https://immunitybio.com/immunitybio-reports-complete-responses-in-non-hodgkin-waldenstrom-lymphoma-patients-with-chemotherapy-free-first-in-class-cd19-car-nk-immunotherapy/
2. First patients dosed in phase 1 clinical study of ImmunityBio’s CAR-NK cell therapy for the treatment of relapsed B-cell non-Hodgkin lymphoma. ImmunityBio. October 24, 2024. Accessed August 14, 2025. https://ir.immunitybio.com/news-releases/news-release-details/first-patients-dosed-phase-1-clinical-study-immunitybios-car-nk
3. Hosseinalizadeh H, Wang LS, Mirzaei H, et al. Emerging combined CAR-NK cell therapies in cancer treatment: Finding a dancing partner. Mol Ther. 2025;33(6):2406-2425. doi:10.1016/j.ymthe.2024.12.057.