Here is a link to the article: https://www.nature.com/articles/s41409-019-0524-2
For those of you who either do not have access to the full article or didn't have time to read it (or couldn't make the live journal club discussion taking place at 9 pm EST on 5/8/19), here is a synopsis of the paper, including key findings:
- This is a retrospective review of all patients with AL amyloidosis transplanted at Mayo between May 1999 and September 2017. Of 696 pts, 41 were excluded for various reasons (including ALREADY BEING ON DIALYSIS AT TIME OF ASCT IN 29 PATIENTS). The remaining 655 pts were divided into "Normal Renal Function" (NRF; eGFR >45 mL/min; n=568) and "Impaired Renal Function" (IRF; eGFR <45 mL/min; n=87)
- Since this wasn't a randomized prospective study, the groups were predictably not balanced for all clinical characteristics. The NRF grp was less likely to have gotten pre-ASCT chemotherapy (41% vs 53%) and more likely to have been treated with a full dose of melphalan as ASCT conditioning (79% vs 29%). Also, the IRF grp had higher cardiac biomarkers (though no statistical difference in Mayo Cardiac Stage distribution) and more patients with advanced Amyloid Renal Stage (0% renal stage 1, compared with 63% in the NRF grp). Cardiac and Renal staging have both been covered in previous #amyloidosisJC sessions.
- 100-day mortality was greater in the IRF grp (14% vs 5%). Risk of progression to ESRD and hemodialysis was also higher in the IRF grp (16% vs 6%). These differences did not have to do with differences in control of the underlying amyloidosis, as the hematologic response rates (88-89%) and complete hematologic response (CR) rates (42-44%) were essentially identical in each grp, though NRF pts who got less than 200 mg/m2 of melphalan had lower CR rates than other patient subsets. There was a higher rate of hospitalizations, a longer duration of hospitalizations, and a higher incidence of culture-confirmed episodes of bacteremia in the IRF group, though causes of death within the first 100 days post-ASCT were not elaborated upon in the article.
- Median Overall Survival (140 mos) and Progression Free Survival (49 mos) were not statistically different between the NRF and IRF gaps.
- The authors provided a thoughtful discussion regarding the limitations and quirks of the trial.
- The period over which patients were treated was long, and eligibility criteria for ASCT evolved over that time. A disproportionate number of pts in the IRF grp were treated in the earlier part of the analyzed period.
- It was difficult to determine whether any of the differences in survival were due to an imbalance of cardiac involvement, because cardiac markers (used to assign Cardiac Stage) are affected by renal clearance
- The definition of "NRF" was not really "N" (that is, a significant number of patients had an eGFR of less than 60 mL/min, though it is not clear exactly how many. The definition of "Renal Stage I" assures us that at least 63% of the NRF pts had an eGFR of at least 50 mL/min).
- During the live #amyloidosisJC session, we will dive into the details a bit further, and also review what others have published in this area. Pertinent articles:
- BU retrospective analysis of ASCT in AL pts (and a few with Monoclonal Immunoglobulin Deposition Disease) on hemodialysis
- BU retrospective analysis of impact of hypoalbuminemia on toxicity from high-dose melphalan pre-ASCT
- Mayo Clinic retrospective analysis of ASCT outcomes in AL pts on hemodialysis
Looking forward to a lively discussion at #amyloidosisJC!