Publication Date:
2018-11-29
Description:
BACKGROUND & METHODS Cfz/Dex is a standard of care in relapsed MM, and renal impairment is a poor prognostic factor. The ALLG MM16 trial was initiated to assess the feasibility of treating patients (pts) who have significant RI (eGFR 15 - 40 ml/min) with Cfz/Dex, and to determine whether an early reduction in serum free light chains (SFLC), with a short half-life, could predict renal outcome. A pre-planned interim analysis was conducted after Cycle 1 of the 32nd registered pt, to assess disease and renal response, predictive value of early SFLC measurements and tolerability. Of concern was whether acute kidney injury (AKI) in the early stages of Cfz treatment may be more common in pts with RI. eGFR was calculated using the MDRD formula. SFLC was measured by the FreeLite assay. RESULTS Patient characteristics Mean age was 56.7 ±1 yr; Stage II/III: 4/28. Median eGFR at enrolment was 27 (IQR 21-32) ml/min. The first 11 pts received Cfz 20/27 mg/m2. After a safety analysis, the next 21 pts were treated at 20/56 mg/m2. Twelve pts were treatment naïve (TN) (all receiving 20/56) and 20 pts had relapsed MM (median 3 prior lines; range 1 - 8). One to 29 cycles were administered, median 4.5 in 20/27 and 4 in 20/56 group. Median follow up was 5.1 (0.1 - 26.5) months. Disease Response Of pts who received ≥4 cycles, 83% achieved ≥PR. In TN pts, best response rates were sCR 33%, CR 17%, VGPR 33%, PR 17%; in relapsed pts, CR 17%, VGPR 25%, PR 33%, PD 25%. Renal response After the first 2 cycles, 24% of pts had a complete renal response (IMWG criteria). To determine if Cfz acutely worsened eGFR, change in eGFR from baseline to day 7 (D7) and D28 was calculated. D7 eGFR showed substantial improvement in TN compared to relapsed pts (+5.6 vs -1.2 ml/min). At D28, the improvement in TN vs relapsed pts (+21.4 vs +3.5 ml/min), and in the 20/56 vs 20/27 group (+14.2 vs +3.5 ml/min) was more pronounced. Comparable results were seen in serum creatinine. Early free light chain kinetics Mean change in involved SFLC after 1 & 2 cycles were -54.5% and -67.0% respectively, with mean increase in eGFR of 9.3 and 11.4 ml/min. Involved LC reduction was significantly greater in 20/56 vs 20/27 doses (at C2D1, 81 vs 13%; p
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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