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Treatment with an allogeneic CD19-directed CAR natural killer–cell therapy led to an ongoing complete response at 15 months in Waldenstrom lymphoma.
The allogeneic CD19-directed CAR natural killer (NK)–cell therapy CD19 t-haNK generated durable disease control in 4 patients with Waldenstrom non-Hodgkin lymphoma, including 2 ongoing complete responses (CRs) at 7 and 15 months, respectively, according to data from the phase 1 QUILT-106 trial (NCT06334991).1
Findings announced by Immunity Bio showed that as of data cutoff, the disease control rate (DCR) was 100% in the 4 evaluable patients.
The 2 patients in ongoing CR received no additional treatment beyond the initial 4 cycles of treatment, which comprised 8 doses of CD19 t-haNK and 6 doses of rituximab (Rituxan). The CRs were reported following 4 doses of the CAR NK-cell therapy and rituximab. The patient in 7-month CR had complete bone morphological remission after presenting with multiple lymphomatous bone lesions at baseline. The other had approximately 95% bone marrow infiltration by tumor cells at baseline and was in ongoing CR at 15 months.
“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, stated in a news release. “Seeing complete responses 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 Waldenstrom lymphoma and validates CAR NK[-cell therapy] as a potential next-generation immunotherapy platform.”
QUILT-106 is evaluating CD19 t-haNK, an off-the-shelf, allogeneic CAR NK-cell therapy designed to express CD19-specific CAR and a high-affinity CD16 receptor in order to drive a pair of antitumor mechanisms: direct CAR-mediated cytotoxicity and augmented antibody-dependent cellular cytotoxicity when given in tandem with the anti-CD20 monoclonal antibody rituximab.
The first-in-human, open-label trial is enrolling patients at least 18 years of age with histologically documented CD19- and CD20-positive B-cell non-Hodgkin lymphoma who have received at least 2 prior lines of cytotoxic chemotherapy, were treated with prior rituximab or another anti-CD20 antibody, and have measurable disease per Lugano classification within 8 weeks of enrollment.2 Other key inclusion criteria include an EGOC performance status of 0 or 1 and a life expectancy of more than 16 weeks.
The study is excluding patients with primary central nervous system lymphoma, chronic lymphocytic leukemia, Burkitt lymphoma, or Burkitt-like lymphoma.
In the first 21-day cycle, enrolled patients are receiving 2 doses of CD19 t-haNK alone.1,2 After a 1-week safety pause, CD19 t-haNK plus rituximab are being given in cycle 2, followed by the first tumor assessment.2 Those without evidence of progressive disease are eligible to receive 2 additional cycles of CD19 t-haNK plus rituximab, with total treatment comprising 8 doses of CD19 t-haNK and 6 doses of rituximab over 4 cycles.1,2 All treatment is being administered in the outpatient setting.1
Safety is serving as the trial’s primary end point; best tumor response per Lymphoma Response to Immunomodulatory Therapy Criteria is a secondary end point.2
Trial enrollment is ongoing, and additional results will be released as additional patients are evaluated and data continue to mature.1
“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, added in a news release. “To date, all patients have been treated as outpatients with no serious adverse effects, demonstrating the feasibility of delivering potent cellular immunotherapy without the morbidity traditionally associated with cell-based treatments.”
