BACKGROUND: Advanced multiple myeloma (MM) and Waldenströ m's macroglobulinemia (WM) are incurable B-cell malignancies. This is the first full clinical report of atacicept, a fusion protein that binds to and neutralises the B-cell survival factors, B-lymphocyte stimulator (BLyS) and A proliferation-inducing ligand (APRIL), in MM and WM. METHODS: In this open-label phase-I study, 16 patients with advanced disease (12 MM, 4 WM) received one cycle of five once-weekly subcutaneous injections of atacicept (2, 4, 7 or 10 mg kg À1 ). Patients with stable disease after cycle 1 entered an extension study (either two additional cycles (2, 4 and 7 mg kg À1 cohorts) or 15 consecutive weekly injections of atacicept 10 mg kg À1 ).

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Interleukin-6 (IL6) is able to stimulate thrombopoiesis in vitro and in vivo in murine and primate models.',' A phase I trial of recombinant IL-6 in humans has demonstrated the capacity of this cytokine for increasing platelet counts in vivo.' However, the physiologic role of IL-6 in the regulation of thrombopoiesis remains unclear." Increased serum IL-6 levels have been reported in patients with reactive thrombocytosis but the causative role of IL-6 for thrombocytosis has not been e~tablished.~ We report here on the role of IL-6 in paraneoplastic thrombocytosis associated with metastatic renal carcinoma. We previously showed that serum IL-6 is increased in a subgroup of patients with renal cell carcinoma.6 The possible correlation between serum IL-6 measured with the B9 bioassay and thrombocyte counts was investigated in a series of I00 patients with metastatic renal cell carcinoma. The 26 patients with undetectable serum IL-6 had a mean platelet number of 3.12 X 105/pL compared with 3.62 X 105/pL in the 5 1 patients with detectable serum IL-6 less than 10 U/mL (Mann-Whitney, P = .04) and 4.72 X 105/pL for the 23 patients with serum IL-6 greater than 10 U/mL (P = .001). CORRESPONDENCE able to normalize thrombocytosis in patients with metastatic renal carcinoma. This demonstrates that an overproduction of IL-6 in vivo is responsible for the paraneoplastic thrombocytosis associated with renal cell carcinoma.