Pioneering Progress: ZYNLONTA and Rituximab Combo Delivers Striking 96% Overall Response in Relapsed Follicular Lymphoma

ZYNLONTA stands as an innovative CD19-directed antibody-drug conjugate (ADC). Upon binding to a cell expressing CD19, ZYNLONTA undergoes internalization, releasing a pyrrolobenzodiazepine (PBD) payload by enzymatic processes within the cell. 

The clinical trial is strategically designed to assess the combination’s efficacy in patients with relapsed or refractory follicular lymphoma with ≥1 line of systemic therapy, and exhibit GELF criteria or experience disease progression within 24 months (POD24) before enrollment. The interim findings presented at the ASH 2023 demonstrated that, as of the data cutoff on November 26, 2023, a total of 27 patients have been assessed for efficacy, while 32 patients have undergone evaluation for toxicity. The treatment demonstrated an outstanding overall response rate of 96.3%, with an impressive complete response rate of 85.2%. Following a median follow-up period of 9.7 months, the median progression-free survival (PFS) was not reached. Notably, the 12-month PFS stands at a robust 92.3%.

Regarding safety evaluation, the predominant share of adverse events (AEs) observed was of grade 1 severity. Moreover, the Grade 3 AEs encompassed instances such as neutropenia (6.2%), and singular occurrences (3.1%) of hyperglycemia, increased ALT, fatigue, dyspnea, and skin infection. Notably, neutropenia stood out as the sole Grade 4 AE, occurring in one case (3.1%).

Based on the initial results, the investigators are planning a multicenter clinical trial aiming to expand the current cohort and decrease the length of therapy to six cycles. The trial is expected to be launched in the first quarter of 2024.

KOL Insights

“In this first-ever study evaluating the combination of ZYNLONTA and rituximab in patients with relapsed or refractory follicular lymphoma, the overall response rate was 96% and the complete response rate was 85%, with a significant number of patients achieving an early response. We believe the high early response rates highlight the exciting potential of ZYNLONTA to be used in combination with an established therapy to improve the treatment paradigm for patients with high-risk follicular lymphoma, including those with POD24, high disease burden and/or advanced disease, whose disease progresses after first-line therapy.”–Expert Opinion.

Conclusion

The preliminary outcomes from the Investigator-Initiated Phase II Clinical Trial assessing the combination of ZYNLONTA with Rituximab have revealed a substantial clinical advantage for patients with relapsed or refractory follicular lymphoma. Notably, a striking 96% overall response rate and an impressive 85% complete response rate underscore the promising therapeutic potential of this combined approach. These findings contribute compelling evidence supporting the efficacy of ZYNLONTA in combination with Rituximab, marking a significant stride toward improving outcomes for patients facing the challenges of relapsed or refractory follicular lymphoma.

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