HIGH RATE OF DURABLE COMPLETE REMISSION IN FOLLICULAR LYMPHOMA AFTER CD19 CAR‐T CELL IMMUNOTHERAPY
Bibliographic record
Abstract
Introduction: Patients (pts) with follicular lymphoma with early relapse after initial chemoimmunotherapy have limited survival, as do those who fail multiple regimens or develop histologic transformation to large cell non-Hodgkin lymphoma (NHL). Initial responses after CD19-directed chimeric antigen receptor (CAR)-modified T (CAR-T) cell immunotherapy in pts with follicular lymphoma have been reported; however, the incidence and durability of responses in pts with follicular lymphoma without transformation (FL) or with histologic transformation (tFL) have not been established. Methods: We conducted a phase 1/2 clinical trial (NCT01865617) of CD19 CAR-T cell immunotherapy in adults with relapsed/refractory (R/R) CD19+ B-cell malignancies. Best responses were reported according to the Lugano criteria. Fisher's exact and Wilcoxon rank-sum tests were used to compare categorical and non-categorical variables, respectively. Results: Twenty-one pts who received cyclophosphamide and fludarabine lymphodepletion followed by 2x106 CD19 CAR-T cells/kg are included in this study. Eight pts (38%) had FL and 13 (62%) had tFL. The FL pts had received a median of 4 prior therapies (range, 2-7); all had failed chemoimmunotherapy with an anti-CD20 antibody and alkylating agents; 75% had progressive disease after the last therapy; and 50% had failed prior autologous (n=3) or allogeneic (n=1) hematopoietic cell transplantation. Before lymphodepletion, 75% had stage III or IV disease; 62% had extranodal involvement; and 75% had intermediate or high FLIPI score. Seven of 8 pts with FL achieved complete remission (CR, 88%; 95% CI, 47-99) after CAR-T cells. The median time to CR was 29 days (range, 27-42), and all who achieved CR remained in remission without additional therapy (median follow-up, 24 months). Despite high-risk disease, durable CR was observed in most FL pts, indicating this therapy should be further investigated in larger studies. For the 13 pts with tFL, the best overall response without additional therapy was 46% (95% CI, 20-74), with all responding pts achieving CR. For tFL pts who achieved CR, the median progression-free survival (PFS) was 11.2 months (95% CI, 3.3-NR; median follow-up 38 months). The median PFS for all pts with tFL was 1.4 months (95% CI, 1.2-NR) [Figure 1]. Pts with FL and tFL had comparable baseline and treatment characteristics; however, more tFL pts had elevated lactate dehydrogenase (LDH; FL vs tFL, 13% vs 69%, P = .02) and fewer had bone marrow involvement (50% vs 15%, P = .15). No significant differences were observed between FL and tFL pts in peak CAR-T cell counts in blood, or the incidence and severity of cytokine release syndrome (CRS) or neurotoxicity (NT). No severe (grade ≥3) CRS or NT were observed. Keywords: CD19; follicular lymphoma (FL); T-cells. Disclosures: Hirayama, A: Honoraria: DAVA Oncology. Hay, K: Consultant Advisory Role: Celgene. Vakil, A: Stock Ownership: Nektar Therapeutics. Riddell, S: Consultant Advisory Role: Adaptive Biotechnologies, Cell Medica, Juno Therapeutics, a Celgene/Bristol-Myers Squibb company, and NOHLA; Stock Ownership: Celgene; Research Funding: Juno Therapeutics, a Celgene/Bristol-Myers Squibb company. Maloney, D: Honoraria: Janssen Scientific Affairs, Seattle Genetics, and Roche/Genentech; Research Funding: GlaxoSmithKline, and Juno Therapeutics, a Celgene/Bristol-Myers Squibb company. Turtle, C: Consultant Advisory Role: Caribou Biosciences, Eureka Therapeutics, Precision Biosciences, Aptevo, Humanigen, Juno Therapeutics, a Celgene/Bristol-Myers Squibb company, Kite, a Gilead Company, Nektar Therapeutics, and Novartis; Stock Ownership: Caribou Biosciences, Eureka Therapeutics, and Precision Biosciences; Research Funding: Juno Therapeutics, a Celgene/Bristol-Myers Squibb company, and Nektar Therapeutics.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.014 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".