Efficacy of Daratumumab in Patients With Relapsed/Refractory Myeloma With Renal Impairment

Inclusion Criteria

• Males and females at least 18 years of age.
• Voluntary written informed consent before performance of any study-related procedure.
• Subject must have documented multiple myeloma as defined by the criteria below:

Monoclonal plasma cells in the bone marrow ≥ 10% or presence of a biopsy proven plasmacytoma.

AND any or more of the following myeloma defining events:

• Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically:
• Hypercalcaemia: serum calcium >0.25 mmol/L (>1 mg/dL) higher than the upper limit of normal or >2.75 mmol/L (>11 mg/dL)
• Renal insufficiency: creatinine clearance 177 μmol/L (>2 mg/dL)
• Anaemia: haemoglobin value of >20 g/L below the lower limit of normal, or a haemoglobin value 1 focal lesions on MRI studies
• Prior treatment with at least two lines of treatment that included both bortezomib- and lenalidomide based regimens.
• Documented evidence of progressive disease (PD) as defined by the modified IMWG criteria on or after the last regimen if the patient responded to previous regimens.
• Subjects must have measurable disease as defined by any of the following:
• Serum monoclonal paraprotein (M-protein) level ≥ 1.0 g/dL (except for IgA subtype: ≥ 0.5 g/dL) or urine M-protein level ≥ 200 mg/24 hours; or
• Light chain multiple myeloma: Serum immunoglobulin free light chain ≥ 10 mg/dL (100 mg/L) and abnormal serum immunoglobulin kappa lambda free-light-chain ratio.
• Renal impairment defined as eGFR 470 msec.
• Any of the following:
• Known active hepatitis A
• Patient is seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]). Subjects with resolved infection (ie, subjects who are HBsAg negative but positive for antibodies to hepatitis B core antigen [anti-HBc] and/or antibodies to hepatitis B surface antigen [anti-HBs]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) DNA levels. Those who are PCR positive will be excluded. EXCEPTION: Subjects with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR.
• Known to be seropositive for hepatitis C (except in the setting of a sustained virologic response [SVR], defined as aviremia at least 12 weeks after completion of antiviral therapy).
• Known to be seropositive for human immunodeficiency virus (HIV).
• Amyloidosis, or any prior or concurrent malignancy, except for the following:
• Adequately treated basal cell or squamous cell skin cancer.
• Any cancer (other than in-situ) from which the subject has been disease-free for 3 years prior to study entry.
• Any of the following laboratory test results during screening:
• Absolute neutrophil count ≤ 1.0 × 10^9/L;
• Hemoglobin level ≤ 7.5 g/dL (≤ 4.65 mmol/L);
• Platelet count < 75 × 10^9/L in patients in whom < 50% of bone marrow nucleated cells are plasma cells and < 50x10^9/L in patients in whom more than 50% of bone marrow nucleated cells are plasma cells;
• Alanine aminotransferase level ≥ 2.5 times the upper limit of normal (ULN);
• Pregnant or nursing women.