Building Capacity for Relapsed/Refractory ALL Patients Needing CAR-T Cells: How Do We Prepare?
Bibliographic record
Abstract
Abstract Introduction: The prognosis of relapsed/refractory (r/r) acute lymphoblastic leukemia (ALL) remains poor in adults. Response rates and survival following anti-CD19 chimeric antigen receptor (CAR) T-cells in r/r ALL have exceeded those of other available agents, but comparative studies are still lacking. Although this therapy shows great promise, it involves complex and expensive manufacturing and administration. Our study seeks to understand the response and survival outcomes of a cohort of Canadian patients with ALL treated with current standard therapies to help the Canadian health care system build capacity for anti-CD19 CART therapies for r/r ALL. Methods: We conducted a retrospective chart review of all patients diagnosed with ALL at 2 large Canadian academic hospitals between 2010 and 2015 (Ottawa and Vancouver). All patient, therapy and outcome-based factors were extracted. Included patients were then cross-checked against the eligibility criteria for completed anti-CD19 CART cell trials in r/r ALL, but with an upper age cut-off of 75. Results: 173 patients were diagnosed with ALL over a 5-year period, with median age of 50 (range 16-88). 159 (92%) patients had CD19 reported by flow cytometry, of which 141 were positive at diagnosis. 124 patients (72%) achieved complete remission with induction chemotherapy and 74 patients (43%) relapsed after a median of 11.8 months (range 1-85.6) from diagnosis, of which 29 patients (17%) experienced a second relapse. A total of 63 patients (36%) had an allogeneic stem cell transplant, of which 22 (13%) relapsed after transplant. Patients who relapsed at any point in time survived 5.4 months (range 0.2-55.4). A total number of 62 patients (35.8%) would have been eligible for currently approved anti-CD19 CAR T cell therapy. Reasons for ineligibility were not limited to remission status, but also included CNS involvement, previous solid malignancy, undocumented CD19 status or CD19 negativity, and evidence of kidney or liver dysfunction. The median event-free and overall survival for patients who would have been eligible for FDA-approved anti-CD19 CART cells were 10.3 months (range 0.4-52.3) and 17.3 months (range 0.4-72.6), respectively. Conclusion: Anti-CD19 CAR T cell therapy has shown very promising results based on early phase data in patients with r/r ALL. Canadian patients are expecting this therapeutic option to be available soon, but our health care system needs to prepare for the complexity of this therapy. Our study helps provide "real-world" eligibility and outcomes of adult patients with r/r ALL. This data suggests that about one-third of cases of ALL could be eligible for this new therapy and should help centers build capacity according to how many new cases of ALL are seen per year. Disclosures No relevant conflicts of interest to declare.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.011 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.003 | 0.002 |
| Scholarly communication | 0.004 | 0.002 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.007 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".