S248: SIERRA TRIAL RESULTS WITH A TARGETED RADIOTHERAPY, IOMAB-B, A MYELOABLATIVE CONDITIONING WITH REDUCED INTENSITY TOLERABILITY YIELDS HIGH CR, LONG TERM SURVIVAL IN HSCT INELIGIBLE ACTIVE R/R AML
Bibliographic record
Abstract
Background: Despite recent advances in the treatment of acute myeloid leukemia (AML), prognosis for patients with relapsed, refractory (R/R) disease remains poor. The only potentially curative option for these patients is allogeneic hematopoietic stem cell transplantation (HSCT). However, only a minority reach complete remission (CR) or sufficient disease control to allow for HSCT, and moreover induction and conditioning regimens are poorly tolerated in the older population. Iomab-B (131I-apamistamab) is an anti-CD45 radioimmunoconjugate delivering targeted myeloablative radioactivity to stem cells and leukemic blasts with reduced intensity tolerability. Aims: SIERRA (NCT02665065) is a multi-centre, randomized, controlled phase 3 study comparing the efficacy of Iomab-B based conditioning versus physician’s choice of conventional care (CC) in older, R/R AML with active disease routinely ineligible for HSCT. Primary endpoint was durable CR (dCR), defined as CR ≥6 mos with or without platelet recovery (CRp). Methods: Pts ≥55 years of age with active R/R AML were randomized (1:1) to CC or Iomab-B with fludarabine and total body irradiation (2 Gy) followed by HSCT. CC pts achieving CR received physician’s choice conditioning and HSCT. Pts not achieving CR could crossover (CO) to Iomab-B-based conditioning followed by HSCT. Assessment for CR/CRp occurred between days 28-56 post HSCT or initiation of therapy on the CC arm. Pts in CR/CRp were evaluated for the primary endpoint of dCR 6 mos after achieving initial CR/CRp. Results: Baseline pt characteristics were balanced between both arms. 61% pts failed targeted therapies prior to enrolment, of whom 66% received venetoclax-based therapy. Median time to HSCT was 29 and 66.5 days on Iomab-B and CC arms (CC pts who had CR/CRp), respectively. The median infused activity of Iomab-B was 664.4 and 613.3 mCi in Iomab-B and CO arms respectively with median dose to marrow of 16 Gy in both arms. All pts who received the therapeutic dose of Iomab-B (n=66) underwent HSCT vs 14 (18.2%) on CC arm. Of evaluable pts (Iomab: 59; CC: 64), 44 (74.6%) pts on the Iomab-B arm achieved initial CR/CRp compared to 4 (6.3%) on CC. Durable CR rates were 22% vs 0% (95% CI; 12.29, 34.73; p<0.0001). The median overall survival (OS) was 6.4 vs 3.2 mos for pts receiving Iomab-B-based conditioning followed by HSCT vs non-CO pts on CC arm, respectively. Median OS in the CO vs non-CO cohorts on the CC arm was 7.1 vs 3.2 mos (HR=0.51; 95% CI [0.31, 0.85]; p=0.0078). OS in pts receiving Iomab-B and HSCT achieving dCR (n=13) was 92% and 60% at 1 and 2 yrs respectively (Figure 1). Event-free survival (EFS) at 6 mos on Iomab-B vs CC was 26% vs 0.2% (HR=0.22; 95% CI [0.15, 0.34]; p<0.0001). Iomab-B-based conditioning followed by HSCT was well tolerated with a favourable safety profile, with lower rates of sepsis in pts receiving Iomab-B based conditioning vs pts undergoing standard of care HSCT.Summary/Conclusion: In pts ≥55 yrs with active R/R AML, Iomab-B was able to safely deliver myeloablative doses of targeted radiation to bone marrow. Iomab-B based conditioning with HSCT resulted in rapid engraftment and high initial CR/CRp rates, a favourable toxicity profile and resulted in statistically significant improvement in the pre-specified primary endpoint of dCR. The majority of pts who achieved dCR are long term survivors, in whom OS and EFS was significant. Iomab-B based conditioning was well-tolerated and provided access to HSCT with curative potential in a vulnerable pt population traditionally not considered eligible for HSCT. Keywords: Radioimmunotherapy, Acute myeloid leukemia, Conditioning, Allogeneic hematopoietic stem cell transplant
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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".