Daratumumab in Patients with Multiple Myeloma and Renal Impairment - Real-World Data from a Single-Center Institution

Abstract

Background: Renal impairment is a frequent complication of multiple myeloma (MM) associated with poor prognosis and decreased overall survival; and can complicate drug dosing, limit treatment options and lead to a higher incidence of adverse events. Daratumumab is an anti-CD38 monoclonal antibody indicated for the treatment of patients with MM which does not require dose modification in the setting of renal impairment. Real-world data regarding its efficacy in patients with renal impairment and the rate of renal response are lacking. Methods: We performed a retrospective, single-center analysis of patients with relapsed/refractory MM treated with daratumumab as monotherapy or in combination with novel agents. Patients were grouped by renal function as calculated by their eGFR using the MDRD equation: <30, 30-59, >=60 mL/min/1.73m2. Renal response was defined as an eGFR >= 60 in two consecutive visits for patients with baseline renal impairment. Results: We identified 91 patients who started treatment with daratumumab between 2015-06-11 and 2018-08-16. The median age was 69 years old (range 40-93) and 25% were over the age of 75; 49 patients (54%) were female. Six patients (9%) were Hispanic, 16 (20%) were African American and 57 (71%) were Caucasian. High-risk cytogenetics were present in 58% of patients; defined as the presence of a complex karyotype, 1q gain, t(4;14), t(14;16), t(14;20) or del17p. Patients underwent a median of 5 prior lines of therapy (range 1-13), 45% had received an autologous stem cell transplant, 91% had been exposed to an immunomodulatory agent, 96% to a proteasome inhibitor, and 89% to both. Upon initial treatment, 53 patients (58%) had an eGFR >=60 mL/min/1.73m2, while 27 (30%) and 11 (12%) patients had an eGFR of 30-59 and <30 mL/min/1.73m2, respectively. The overall response rate (ORR) was 81% with a very good partial response (VGPR) or better of 47% and an unconfirmed complete response rate (uCR) of 23%. The median progression-free survival (mPFS) was 17.5 months while median overall survival (mOS) was not reached. There was no difference in mPFS or mOS between renal function groups. Of the 38 patients with baseline renal impairment (eGFR <60 mL/min/1.73m2), 11 patients (29%) achieved a renal response, however, none of these patients had severe renal impairment. When compared to patients with chronic renal impairment, those with acute renal impairment were more likely to achieve a renal response (80% vs 21%, p=0.02). No significant difference in mPFS or mOS was observed by renal response (mPFS: 25.7m vs 17.5m, p=0.2; mOS: NR vs NR, p=0.8). Each renal function group was well balanced for the above parameters, including adverse events of interest and concurrent myeloma therapy as shown in the table, except where indicated (*). Discussion: The results of this analysis provide comparable efficacy - independent of the degree of baseline renal impairment - to the results seen in clinical trials of combination therapy with daratumumab. Furthermore, the high renal response rate (29%) seen, as compared to the one in the subgroup analysis of ENDEAVOR (15%), highlights the utility of daratumumab in reversing renal end-organ damage in patients with relapsed/refractory MM without an increase in adverse events compared to patients with preserved renal function. These results suggest that daratumumab may be able to abrogate the adverse prognostic factor that impaired baseline renal function portends. A limitation of this study is its retrospective nature, the confounding effect of concurrent myeloma therapy and the small number of patients included with renal impairment. Table Disclosures Coleman: Merck: Research Funding; Pharmacyclics: Speakers Bureau; Kite Pharmaceuticals: Equity Ownership; Gilead, Bayer, Celgene: Consultancy, Research Funding, Speakers Bureau. Niesvizky:Takeda, Amgen, BMS, Janssen, Celgene: Consultancy, Research Funding. Rossi:Janssen, Celgene, Amgen: Consultancy; BMS: Research Funding.

Clinically‐suspected cast nephropathy: A retrospective, national, real‐world study

“…The standard frontline treatment in our patient group consisted of CVD induction followed by HDT‐ASCT in transplant‐eligible patients, and VD in transplant‐ineligible patients. Daratumumab is a monoclonal antibody that can be safely administered in patients with renal failure 47,48 . There were only seven patients in our cohort that were treated with daratumumab, which had been reimbursed in Denmark since September 2016.…”

Management of Relapsed–Refractory Multiple Myeloma in the Era of Advanced Therapies: Evidence-Based Recommendations for Routine Clinical Practice

“…Anti-CD38-containing regimens with ISA or DARA have been shown to be effective in patients with renal failure based on the results of subgroup analysis of the ICARIA and IKEMA trials [ 211 , 212 ], as well as real-world data [ 213 , 214 , 215 ]. The DARE trial assessed DARA-dexa in 38 patients with severe renal dysfunction, 50% of whom were on dialysis [ 216 ].…”

An overview of treatment options for patients with relapsed/refractory multiple myeloma and renal impairment

“…Case reports 74 – 77 and a small case series 78 of dialysis-dependent patients with RRMM who received daratumumab-based therapy have consistently reported benefit, in some instances with reduction of dialysis frequency 75 , 76 or full dialysis independence. 74 , 77 A retrospective, single-center study 80 analyzed 91 patients with RRMM who received daratumumab as monotherapy or in combination with novel agents. Patients were grouped by renal function (eGFR < 30 ( n = 11), ⩾ 30 to 60 ( n = 27), and ⩾ 60 mL/min/1.73 m 2 ( n = 53)).…”