Autotransplantation in Patients with Multiple Myeloma and Concurrent Renal Failure Is Safe and Feasible and Associated with Recovery of Renal Function in > 30% of Patients.
Authors: Parikh Gaurav C. , Saliba Rima M. , Lahoti Amit , Hosing Chitra , Mendoza Floralyn , Qureshi Suhail R. , Weber Donna M. , Wang Michael , Popat Uday , Alousi Amin , Champlin Richard E. , Giralt Sergio A. , Qazilbash Muzaffar H. 
Published: October 2019

Background: About 20% of patients with multiple myeloma (MM) have renal impairment at diagnosis and 2–3% are dialysis-dependent (DD). These patients may potentially benefit from high-dose therapy (HDT) and autotransplants.

Method: We analyzed the outcome in 48 patient who received an autotransplant for MM while in renal failure at our institution between 8/1991 and 9/2006. Renal failure was defined as serum creatinine ≥ 2 mg/dl sustained for > 1 month. 9 patients (18%) were DD. Median age was 56 (29–72) years. 26 patients (54%) had at least a PR to induction therapy, 16 had primary refractory disease (33%) and 6 patients (12%) had relapsed disease. Median serum Cr was 2.9 mg/dl (2.0 – 12.5) and creatinine clearance (CrCl) at transplant was 33 ml/min (8.7 – 63). A CrCl of <20 ml/min was seen in 15 patients (31%). PBSC mobilization was performed with G-CSF alone in 37 patients (77%) and chemotherapy + G-CSF in the rest. Median CD34 cell dose was 4.47 x 106 /kg (1.4 – 9.7). Forty-six patients received HD melphalan as preparative regimen, while 2 patients received a combination of thiotepa, busulfan and cyclophosphamide.

Results: 9 patients achieved a CR (19%), with a total response rate (CR + PR) of 67% (32 patients). 2 patients (4%) died within 100 days of autotransplant. Median times to neutrophil and platelet engraftment were 10 (9–18) and 12 (8–81) days, respectively. Grade ≥ 1 mucositis was seen in 21 patients (43%), with 3 patients (6%) experiencing grade ≥3 mucositis. After a median follow up of 34 months, the estimated median PFS and OS were 21 and 87 months, respectively. Kaplan-Meier estimates of 5-year PFS and OS probabilities were 21% and 54%, respectively. Significant improvement in renal function, defined as an increase in Glomerular Filtration Rate by 25% above baseline by 1 year post-transplant, was seen in 17 patients (35%). None of the 9 DD patients became dialysis independent. A pre-transplant creatinine level of ≥ 3mg/dl was associated with a significantly shorter overall survival (p = 0.05, HR 2.8), but did not adversely impact the improvement in renal function (p = 0.6).

Conclusion: Autotransplant after HDT is safe and feasible in patients with multiple myeloma and renal failure. Response rates and outcomes were similar to those observed in other patients. Approximately 35% of patients had a significant improvement in renal function post-transplant.

Analysis Results Ref= Reference N Event Free Survival Overall Survival 48 Hazard Ratio at 3 years 95% CI p value Hazard ratio at 3 years 95% CI p value Age ≤ 55 23 Ref Ref > 55 25 1.2 0.6–2.7 0.6 1.2 0.4–3.1 0.8 Cytogenetics Abnormal 10 0.9 0.4–2.5 0.9 1.7 0.5–6.1 0.4 Normal 27 Ref Ref Pretransplant Dialysis Dependent Yes 9 1.1 0.4–3.4 0.8 1.1 0.4–4.7 0.6 No 39 Ref Ref Serum Creatinine ≥ 3 23 1.6 0.7–3.4 0.2 2.8 1–7.9 0.05 <3 25 Ref Ref