Therapy-Related Myeloid Neoplasms After [<sup>177</sup>Lu]Lu-PSMA Therapy in Patients with Metastatic Castration-Resistant Prostate Cancer: A Case Series
Bibliographic record
Abstract
[177Lu]Lu-prostate-specific membrane antigen (PSMA) therapy has a favorable toxicity profile in patients with metastatic castration-resistant prostate cancer (mCRPC). Therapy-related myeloid neoplasm (t-MN) has been described after [177Lu]Lu-DOTATATE but has not, to our knowledge, yet been reported after [177Lu]Lu-PSMA. This case series describes 5 patients with mCRPC who developed t-MN after [177Lu]Lu-PSMA at our institution. Methods: In this single-center retrospective analysis, we reviewed all patients with mCRPC treated with [177Lu]Lu-PSMA. Patients who developed biopsy-proven t-MN during or after [177Lu]Lu-PSMA treatments are summarized with descriptive statistics. Results: From August 26, 2015, to December 31, 2022, 5 of 381 (1.3%) patients treated with [177Lu]Lu-PSMA were subsequently diagnosed with t-MN. Their median age at cycle 1 (C1) was 78 y (range, 65–80 y). The median time from C1 to t-MN diagnosis was 33.6 mo (range, 6.0–58.8 mo). Previous treatments included docetaxel (n = 5), external-beam radiotherapy to metastases (n = 5), abiraterone (n = 4), enzalutamide (n = 3), and cabazitaxel (n = 3). On PSMA PET/CT, 4 (80%) patients had predominantly bone metastases and 1 (20%) had predominantly nodal metastases. They were treated with [177Lu]Lu-PSMA-617 (n = 3) or [177Lu]Lu-PSMA-I&T (n = 2). A median of 7 cycles (range, 4–12 cycles) of [177Lu]Lu-PSMA was administered, with a median total cumulative activity of 49.2 GBq (range, 31.3–79.0 GBq). Prostate-specific antigen reduction of at least 50% or at least 80% from baseline was seen in 5 (100%) and 4 (80%), respectively. All had prostate-specific antigen progression preceding t-MN diagnosis. t-MN diagnosis included myelodysplastic syndrome with single-lineage dysplasia (n = 2), myelodysplastic syndrome with excess blasts 1 (n = 1), acute promyelocytic leukemia (n = 1), and acute myeloid leukemia (n = 1). At t-MN diagnosis, all patients presented with at least grade 2 cytopenia, involving one or more blood cell lines. Marrow genetic analysis revealed unfavorable karyotypes or mutations in all patients. Most patients received supportive care after t-MN diagnosis. Survival was 8.1, 31.3, 43.0, 56.0, and 60.4 mo from C1 and 1.8, 2.1, 6.8, 10.3, and 12.4 mo from t-MN diagnosis. Conclusion: In the mCRPC population after chemotherapy, we describe a low incidence of t-MN after [177Lu]Lu-PSMA therapy. Ongoing follow-up is necessary to further define the true incidence of t-MN or other unexpected delayed toxicities, particularly with earlier use of [177Lu]Lu-PSMA in the disease course.
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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 | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".