Journal: Blood advances
This publication is a systematic review and pooled analysis focused on patients with follicular lymphoma who experience progression within 24 months of initial treatment (POD24), a group known to have poor prognosis and limited standard options.
Key features and methods:
- Included trials and population: 21 clinical trials with a total of 1242 participants with POD24.
- Endpoints evaluated: overall response rate (ORR), complete response (CR), duration of response, and progression‑free survival.
- Comparisons: when possible, outcomes were compared between POD24 and non‑POD24 patients receiving the same regimen.
- Therapies studied: four trials studied anti‑CD19 CAR T‑cell therapy; others evaluated bispecific antibodies, anti‑CD19 antibody–drug conjugates/monoclonal antibodies, PI3K inhibitors, and anti‑CD20–containing regimens (including lenalidomide combinations).
Main efficacy findings (POD24 population):
- Anti‑CD19 CAR T‑cell therapy:
- Pooled ORR: 91.2% (95% CI, 83.7–98.7).
- Pooled CR: 75.7% (95% CI, 55.1–96.4).
- Study variability: considerable heterogeneity across studies.
- Bispecific antibodies:
- Pooled ORR: 81.6% (95% CI, 75.9–87.3), no significant heterogeneity.
- Pooled CR: 65.7% (95% CI, 57.1–74.3), moderate heterogeneity.
- Anti‑CD19 ADCs/mAbs:
- Loncastuximab + rituximab: ORR 100%, CR 79.3%.
- Tafasitamab + lenalidomide + rituximab (R2): ORR 87.5%, CR 43.2%.
- Other regimens: regimens including PI3K inhibitors and anti‑CD20 mAbs were also examined in pooled analyses, but detailed numbers beyond those in the abstract are not provided here.
Conclusions relevant to practice:
- Highest CR rates: among evaluated options in POD24 follicular lymphoma, anti‑CD19 CAR T‑cell therapy yields the highest complete response rates.
- High activity of other CD19‑directed approaches: bispecific antibodies and anti‑CD19 ADCs/mAbs also show high activity.
- Lenalidomide‑based combinations: lenalidomide‑based combinations with obinutuzumab or rituximab are effective; lenalidomide plus obinutuzumab appears more efficacious than R2 based on the data summarized.
- Overall implication: the work supports CAR T cells as a leading high‑depth option in POD24, with bispecifics, targeted CD19 approaches, and optimized lenalidomide–anti‑CD20 combinations as strong alternatives in this high‑risk group.