Study Finds Autologous Stem Cell Transplantation Safe, Effective in Patients With Multiple Myeloma, Chronic Kidney Disease

Autologous stem cell transplantation (ASCT) is a well-established treatment strategy for multiple myeloma (MM) in remission after induction or salvage therapy. However, there has been debate and conflicting findings regarding the safety of ASCT in patients who also have chronic kidney disease (CKD), a common complication in MM. A recent study aimed to provide insight into the safety and effectiveness of ACST in MM patients with CKD.

Approximately 10% of patients with MM also present with CKD or acute kidney injury (AKI) at the time of MM diagnosis, and almost 50% of patients with MM experience CKD or AKI at some point. Advanced CKD that requires long-term dialysis occurs in about 10% of MM patients, and renal impairment (RI) is associated with worse mortality and morbidity in MM patients.

Overall survival (OS) and progression-free survival (PFS) rates have improved as novel agents such as bortezomib, lenalidomide, and thalidomide have been integrated into the treatment repertoire, and early treatment can help improve renal function in many patients.

ASCT, however, has become a controversial treatment for MM patients with CKD. Several studies have shown ASCT to improve life expectancy and outcomes in patients with RI in addition to MM, and another study showed ASCT to be safe in patients with moderate to severe CKD. But considering a recent study that identified CKD as an independent risk factor for AKI post ASCT in patients with MM, the treatment has become controversial in this patient population.

The current study, published in Bone Marrow Transplantation, was a retrospective observational study of 370 patients with MM who underwent ASCT at a large transplant center in the United Kingdom. The main outcomes of interest were transplant-related mortality (TRM), PFS, and OS in patients with and without CKD. ASCT effects on renal function were also explored.

Median patient age was 60 years, and 22% of patients were older than 65 years. Median time from diagnosis to ASCT was 10.4 months, and 81% of patients received 1 line of chemotherapy ahead of transplant, whereas the remaining patients received more than 1 line prior to ASCT. Overall, 93% of patients received novel agents during induction therapy—of the overall cohort, 86% of patients were treated with thalidomide and/or bortezomib, and 7% were given lenalidomide.

Estimated glomerular filtration rate (eGFR) determined renal function status, with patients stratified into 4 groups based on the following eGFR ranges at the time of transplant: Group 1 (7% of patients) had an eGFR of less than 30 mL/min/1.73 m², group 2 (11% of patients) had an eGFR of 30 to 59 mL/min/1.73 m², group 3 (46% of patients) had an eGFR of 60 to 89 mL/min/1.73 m², and group 4 (36% of patients) had an eGFR of at least 90 mL/min/1.73 m². All 370 patients had eGFR data available at the time of transplant, 328 had data available at 100 days post transplant, and 307 had data available at 1 year post transplant.

At the time of ASCT, 64% of patients had an eGFR lower than 90 mL/min/1.73 m², and there was no significant difference in median eGFR in the entire cohort at transplant vs 1 year post transplant. Regarding individual changes in eGFR, a paired analysis showed an improvement in renal function at 1 year post transplant, the authors noted.

There was no significant worsening of renal function post transplant in any patients, even those with moderate or severe CKD. Of 11 patients who were dialysis dependent at the time of transplant, 7 became dialysis free post transplant, of whom 4 received successful kidney transplants.

Post ASCT, the 5-year survival rates in eGFR categories 1, 2, 3, and 4 were 71%, 66%, 67%, and 71%, respectively. Rates of PFS were not significantly different between eGFR groups, and neither were rates of TRM at 100 days post transplant.

Individual changes in eGFR were calculated and grouped into quartiles, and researchers found that patients who experienced an eGFR reduction greater than 8.79% had worse OS vs quartiles with less severe drops in eGFR at 1 year post ASCT.

“The baseline characteristics of the four groups were similar supporting the hypothesis that the observed difference in outcomes was due to changes in eGFR and not to other confounding factors,” the authors wrote. Patients with reduced eGFR at 1 year post transplant should therefore be monitored more closely, they noted.

Overall, the findings suggest that ASCT is a safe therapy option in MM, even in patients with CKD. The results align with other studies that have shown renal function improvement in MM patients with reduced eGFR after ASCT.

“This study clearly demonstrates the safety of performing ASCT in MM patients with CKD including those requiring dialysis with no negative impact on neutrophil or platelet engraftment or increase in TRM observed,” the study authors wrote. “Furthermore, there was no difference in OS and PFS between patients with and without reduced eGFR even in those with more advanced CKD, in keeping with results from other studies.”

Reference

Lazana I, Floro L, Christmas T, et al. Autologous stem cell transplantation for multiple myeloma patients with chronic kidney disease: a safe and effective option. Bone Marrow Transplant. Published online April 12, 2022. doi:10.1038/s41409-022-01657-y