CD19 t-haNK Leads to Complete Responses in Waldenstrom Macroglobulinemia

The CD19-directed CAR-NK cell therapy CD19 t-haNK displayed encouraging responses in patients with late-stage Waldenstrom macroglobulinemia (WM), according to preliminary data from the phase 1 QUILT-106 study (NCT06334991).1

Initial data from QUILT-106 revealed that the first 2 patients treated with CD19 t-haNK achieved complete responses (CRs). Both patients were heavily pretreated. One patient achieved a CR with CD19 t-haNK monotherapy and the other experienced a CR following treatment with CD19 t-haNK in combination with rituximab (Rituxan). The remissions were maintained and, to date, are ongoing for 6 months. In terms of safety, the regimens were tolerable, and no significant toxicities were reported.

“The preliminary findings we have submitted for presentation at the American Society of Hematology Annual Meeting provide the first evidence that novel immunotherapy combinations without chemotherapy lymphodepletion can provide deep and durable remissions in [patients with] WM even after multiple prior treatments,” Jackie Thomson,MBChB, MMed, a clinical hematologist and the director of the Transplant Program at Wits University Donald Gordon Medical Center in Johannesburg, South Africa, and the lead author of the study, stated in a news release. “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.”

CD19 t-haNK is a high-affinity, off-the-shelf, allogeneic natural killer cell line that is designed to express a CD19-specific CAR and a high-affinity CD16 (FcγRIIIa 158V) receptor. The agent employs dual antitumor mechanisms: direct CAR-mediated cytotoxicity and augmented antibody-dependent cellular cytotoxicity when given in combination with rituximab.

QUILT-106 is the first-in-human trial of CD19 t-haNK.2 The open-label study is enrolling adult patients with relapsed/refractory B-cell non-Hodgkin lymphoma (NHL). In order to be eligible for the trial, patients must have CD19- and CD20-positive B-cell NHL (excluding primary central nervous system (CNS) lymphoma, chronic lymphocytic leukemia, and Burkitt lymphoma) and have completed at least 2 lines of cytotoxic chemotherapy and received rituximab or another anti-CD20 antibody. Also required is measurable disease per Lugano classification within 8 weeks of the time of consent, and a minimum of 5% CD19 and CD20 positivity per immunohistochemistry or flow cytometry. Additional eligibility criteria include an ECOG performance status of 0 or 1 and a life expectancy exceeding 16 weeks.

Exclusion criteria include a history of allogeneic hematopoietic stem cell transplantation requiring ongoing systemic graft-vs-host disease therapy, receipt of an anti-CD20 antibody treatment less than 2 weeks prior to cell infusion, a history of allograft organ transplant requiring immunosuppression, and CD19- and CD20-positive metastases to the CNS.

Eligible patients will be treated with CD19 t-haNK monotherapy or CD19 t-haNK in combination with rituximab. Patients will initially receive a single 3-week cycle of CD19 t-haNK monotherapy. After a 1-week safety pause, patients will then be treated with CD19 t-haNK in combination with rituximab via a 3-week cycle, followed by tumor assessment. Patients without evidence of disease progression will be eligible to receive two additional 3-week cycles of CD19 t-haNK plus rituximab.

All patients will be treated with at least 1 dose of CD19 t-haNK. The first 3 patients will receive CD19 t-haNK via a staggered dosing schedule with a 7-day interval between each patient to evaluate toxicities.

The primary end points of QUILT-106 are overall safety as well as the incidence of treatment-emergent adverse effects (AEs) and serious AEs. The secondary end point is best tumor response per Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC). Responses will be assessed by the investigator after the completion of cycle 2 (± 1 week) and at the end of therapy per PET/CT by LYRIC.

References

1. ImmunityBio reports complete responses in non-hodgkin Waldenstrom lymphoma patients with chemotherapy-free, first-in-class CD19 CAR-NK immunotherapy. News release. 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. Study for subjects with relapsed/​refractory non-Hodgkin lymphoma. ClinicalTrials.gov. Updated January 14, 2025. Accessed August 13, 2025. https://clinicaltrials.gov/study/NCT06334991