Allo-CAR-NK Therapy & Rituximab: Long-Term Remission in Waldenstrom NHL

Two patients with Waldenström’s non-Hodgkin’s lymphoma (NHL) are still in complete remission—for 7 and 15 months, respectively—after a novel treatment combining off-the-shelf chimeric antigen receptor (CAR) natural killer (NK) cell therapy with rituximab, according to an update shared by ImmunityBio on Friday.¹ This offers a potentially groundbreaking, chemotherapy-free approach to a rare and challenging cancer.

The promising results stem from the ongoing QUILT-106 clinical study (NCT06334991) and offer hope for patients who haven’t responded to standard treatments. This new therapy is the first of its kind—chemotherapy-free and without the need for lymphodepletion—to demonstrate 100% disease control in its initial four patients, all treated as outpatients.¹

A New Approach to Waldenström’s Lymphoma

The treatment utilizes ImmunityBio’s allogeneic cell therapy, engineered to express a CD19-specific CAR NK cell and a high-affinity CD16 (FcγRIIIa 158V) receptor. This dual-action design amplifies the tumor-fighting effect when combined with rituximab, an anti-CD20 monoclonal antibody.¹ Rituximab works by targeting CD20 on B cells.²

Waldenström’s NHL is a rare B-cell malignancy with significant unmet medical needs. Patients who experience relapse or become resistant to existing targeted and antibody-based therapies face limited options.¹

Did you know? Waldenström’s macroglobulinemia is a type of non-Hodgkin lymphoma that affects the bone marrow, blood, and other organs.

Patients in the QUILT-106 study received eight doses of cell therapy in an outpatient setting, bypassing the need for chemotherapy-based lymphodepletion. The treatment strategy involved targeting tumors with both CD19 and CD20 by infusing CD19 CAR NK cells alongside rituximab—two doses per cycle every 21 days for four cycles (eight NK-CAR doses and six rituximab doses), followed by no further therapy. Responses were assessed after two cycles.

The two patients currently in long-term follow-up continue to experience complete remission without any additional treatment, according to the company’s statement.¹

Both the rapid onset of remission and its durability suggest the potential for long-term, immune-mediated disease control without continuous therapy, aligning with the growing trend toward time-limited regimens that reduce patient toxicity and lower healthcare costs.³

“This updated follow-up reinforces our belief that restoring and activating the immune system can achieve durable disease control without chemotherapy or lymphodepletion,” said Patrick Soon‑Shiong, MD, founder, executive chairman, and global chief medical and scientific officer of ImmunityBio. “Seeing complete responses persist for over a year after treatment cessation, in patients who had exhausted all other options, represents a significant advancement for those with Waldenström lymphoma and validates CAR-NK as a promising next-generation immunotherapy platform.”¹

One patient initially presented with multiple cancerous lesions in the bones, while the other had tumor cells infiltrating approximately 95% of their bone marrow. Both achieved complete responses after just four doses of CAR-NK therapy combined with rituximab.

Company officials noted that the patient with significant bone marrow involvement experienced complete bone marrow remission. In this case, tumor cells had replaced 95% of the bone marrow, but after only four doses, the patient achieved a complete remission that has now been sustained for 15 months, with no further treatment.¹

This approach “eliminates the need for cytotoxic conditioning for lymphodepletion or inpatient hospitalization, addressing key limitations associated with conventional CAR-T therapies,” ImmunityBio officials explained.¹

“These data highlight a favorable safety and efficacy profile that is particularly important for patients with indolent yet incurable lymphomas,” added Lennie Sender, MD, ImmunityBio’s chief medical officer for liquid tumors and cell therapy.¹ To date, patients have not experienced any serious adverse events, Sender reported.¹

ImmunityBio is planning a follow-up study that will combine the CAR-NK therapy, rituximab, and the company’s nogapendekin alfa inbakicept treatment, an immunotherapy currently approved by the FDA in combination with Bacillus Calmette-Guérin (BCG) for BCG-unresponsive nonmuscle invasive bladder cancer (NMIBC) with carcinoma in situ.⁴ This triplet will be evaluated in indolent lymphoma, including Waldenström’s macroglobulinemia.¹

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 17, 2026. https://ir.immunitybio.com/news-releases/news-release-details/immunitybio-announces-durable-complete-response-15-months
2. Maloney DG. Mechanism of action of rituximab. Anticancer Drugs. 2001;12(suppl 2):S1-4.
3. Caffrey M. Time-limited regimens gain notice, offering a break for patients with blood cancer and savings for payers. Am J Manag Care. 2026;32(Spec 1):SP12.
4. FDA approves nogapendekin alfa inbakicept-pmln for BCG-unresponsive non-muscle invasive bladder cancer. News release. April 22, 2024. Accessed January 17, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-nogapendekin-alfa-inbakicept-pmln-bcg-unresponsive-non-muscle-invasive-bladder-cancer