ImmunityBio has reported encouraging early results from its QUILT-106 Phase I trial, demonstrating complete responses in the first two patients with late-stage Waldenstrom macroglobulinemia (WM) treated with its CD19 CAR-NK natural killer cell therapy. The findings represent the first evidence that chemotherapy-free immunotherapy combinations can achieve deep and durable remissions in this challenging-to-treat form of non-Hodgkin lymphoma.
Trial Design and Patient Population
QUILT-106 (NCT06334991) is a first-in-human, open-label study evaluating the safety and preliminary efficacy of CD19 CAR-NK cell therapy alone and in combination with rituximab in patients with relapsed or refractory CD19⁺CD20⁺ B-cell non-Hodgkin lymphoma. The study, sponsored by ImmunityBio and led by Dr. Glenda Gray, has enrolled 13 patients with NHL at three sites in South Africa, with three patients having WM.
Eligible participants express CD19 and CD20 markers and have active disease after at least two chemotherapy-based lines of treatment. The treatment protocol involves a lead-in cycle of CD19 CAR-NK cell monotherapy, followed by a one-week safety observation pause, then a second cycle combining CD19 CAR-NK with rituximab. Key endpoints include safety/tolerability and objective response rate by standard criteria.
Clinical Outcomes
In the first two evaluable WM patients who were heavily pretreated, the entirely chemotherapy-free immunotherapy regimen induced encouraging responses. One patient achieved a complete response with CD19 CAR-NK monotherapy, while the second patient achieved complete response with CD19 CAR-NK in combination with rituximab. Remission was maintained and is ongoing for six months to date.
Both patients tolerated the regimen with no significant toxicities, and notably, all infusions including CAR-NK cells and cytokines were administered in an outpatient setting.
"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," said Dr. Jackie Thomson, Wits University Donald Gordan Medical Center, Johannesburg, South Africa and the lead author of the paper.
Therapeutic Mechanism
CD19 CAR-NK is a targeted high-affinity natural killer cell therapy—an off-the-shelf, allogeneic NK cell line engineered to express a CD19-specific chimeric antigen receptor (CAR) and a high-affinity CD16 (FcγRIIIa 158V) receptor. This design enables dual anti-tumor mechanisms: direct CAR-mediated cytotoxicity and augmented antibody-dependent cellular cytotoxicity when paired with anti-CD20 monoclonal antibody rituximab. Combining CD19 CAR-NK cells with rituximab could thereby target CD19⁺/CD20⁺ lymphoma cells to enhance tumor cell killing.
Clinical Significance
WM remains challenging to treat and is considered incurable with existing treatment options, making novel immunotherapies an important avenue of exploration for potential effective treatments. The results validate the power of NK cells in treating this rare subset of lymphoma and establish this chemotherapy-free strategy as a potentially viable treatment option for relapsed WM.
Dr. Thomson noted that "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."
