High Progression-Free Survival At 10 Years After Tandem Autologous/Nonmyeloablative Allogeneic Transplants For Multiple Myeloma In a Cohort Of 93 Patients: Impact Of Disease Remission Status At Transplant and Chronic Graft-Versus-Host Disease
Bibliographic record
Abstract
Abstract Introduction Despite improved survival with new molecules, allogeneic hematopoietic stem cell transplantation (alloHSCT) remains the only curative option for multiple myeloma (MM). Myeloablation with autologous HSCT (autoHSCT) followed by nonmyeloablative (NMA) alloHSCT has reduced the high nonrelapse mortality (NRM) rates associated with myeloablative alloHSCT, but randomized trials comparing NMA alloHSCT with standard therapy have yielded conflicting results. Factors affecting long-term outcomes have not been clearly defined. We sought to identify factors associated with outcomes in a large single-center cohort of 93 tandem transplant recipients. Methods We conducted a prospective phase II trial in Durie-Salmon (DS) stage II/III newly diagnosed MM patients <65 years with a 6/6 sibling donor, characterized by outpatient alloHSCT and complete immunosuppression withdrawal by day +100. Following induction therapy, patients received autoHSCT followed 3 months later by an outpatient NMA alloHSCT. Conditioning regimen consisted of fludarabine (30 mg/m2 x 5 days) and cyclophosphamide (300 mg/m2 x 5 days), followed by donor G-CSF mobilized stem cells (target dose: ≥4 x 10^6 CD34+/kg). GVHD prophylaxis included tacrolimus (day -10 to +50, taper by +100) and mycophenolate mofetil 1000 mg BID (day +1 to +50). Probabilities of overall and progression-free survival (OS and PFS), relapse, NRM and graft-versus-host disease (GVHD) incidences were estimated taking competing risks into account when appropriate. Regression analysis using Cox and Fine & Gray models were used to determine factors influencing outcomes. Severity of chronic GVHD was assessed by the proportion of alive patients on systemic immunosuppression. Results From 2001 to 2010, 93 patients received tandem HSCT from a matched sibling donor; median age was 52 years (range 39-64) and DS stage III present in 76%. All but 6 patients received a single line of induction therapy. Median time from diagnosis to autoHSCT and from auto- to alloHSCT were 7 (range 3-57) and 4 (range 2-13) months, respectively. At least partial remission (PR) status was obtained in 84% patients before tandem HSCT. After a median follow-up of 7 years, cumulative incidences of grade II-IV acute and extensive chronic GVHD were 9% (95%CI: 4-15) and 85% (75-91) respectively. Cumulative incidences of NRM and progression were 10% (95%CI: 3-22) and 47% (37-58; Fig. 1). Probability of 10-year OS and PFS were 64% (50-74; Fig. 2) and 44% (31-56; Fig. 1) respectively. In multivariate analysis, at least stable disease (SD) status before alloHSCT was a significant protective factor for progression incidence and PFS (respectively, HR 0.18, CI: 0.05-0.64, and HR 0.12, CI: 0.04-0.36). Extensive chronic GVHD as time-dependent variable was also protective for PFS (HR 0.39, CI: 0.19-0.80). The most significant protective factor for OS was at least SD status before alloHSCT (HR 0.15, CI: 0.04-0.56). The association between chronic GVHD and OS did not reach statistical significance. In survivors, the probability of being on systemic immunosuppressive treatment for GVHD was 39% (CI: 27-52) at 5 years and 15% (CI: 4-42) at 10 years. Conclusions We report a very high PFS of 44% at 10 years in a large cohort of 93 NMA alloHSCT recipients. Despite the high incidence of chronic GVHD, we observed a low NRM of 10% and an acceptable prevalence of immunosuppressive therapy of 15% at 10 years. Chronic extensive GVHD and achievement of disease control before HSCT were both associated with better PFS. Patients with progressive disease do not seem to benefit from NMA alloHSCT and efforts to reduce chronic 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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 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".