A Trial for Relapsed and Relapsed/Refractory Multiple Myeloma Patients

Multiple myeloma (MM) with chromosome 17 deletion (del(17p) represents one of the most dangerous genetic variant of this disease, since it is associated with a high level of genomic instability. Del(17p) is present in approximately 10% of patients at diagnosis, and its frequency increases with disease evolution. The adverse prognosis of del(17p) has been observed in patients treated with conventional chemotherapy and new drugs. Only very few studies have suggested an advantage in treating del(17p) MM patients with specific therapies. In particular, several recent trials combining lenalidomide plus dexamethasone with a new agent, suggested that high risk cytogenetics patients may benefit from newest generation drugs. Yet, in all studies, outcome of patients with high risk genetic features have been derived from subgroup analyses, with all the limitations of this approach. To date no trial has been designed with the specific aim to test genotype-adapted therapies. The objective of the present study is to evaluate the combination of daratumumab-pomalidomide-dexamethasone (DPd) in relapsed or relapsed/refractory MM patients harboring del(17p). Treatment of relapsed or relapsed/refractory MM patients harbouring del(17p) is a relevant unmet medical need. A clinical trial designed to test a tailored treatment for this patient population would be a major improvement. In this perspective the combination DPd seems attractive since: * both daratumumab and pomalidomide are therapies not interfering with DNA replication, thus not increasing the intrinsic genomic instability of del(17p) plasma cells. * the POLLUX study has shown that daratumumab in combination with lenalidomide is highly effective in relapsed and relapsed/refractory MM patients.10 * the IFM 2010-02 trial has suggested that pomalidomide may be effective in del(17p) patients. * the DPd combination has been successfully tested in MM patients with advanced disease.

Inclusion Criteria: * Patient has given voluntary written informed consent * Subject must be at least 18 years of age. * Subject must have documented MM. * Subject must have del(17p) observed by FISH in at least 10% of bone marrow plasma cells at any time of MM history. * Subject must have serum monoclonal paraprotein (M-protein) level \>=0.5 g/dL or urine M-protein, level \>=200 mg/24 hours, or light chain MM, or serum immunoglobulin free light chain ≥10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio. * Subject must have received at least 1 and no more than 3 prior lines of therapy for MM. * Subject must have received at least 2 consecutive cycles of lenalidomide in a previous line of therapy. * Subject must have achieved a response (PR or better) to at least one prior regimen. * Subjects must have either refractory or relapsed and refractory disease defined as documented disease progression during or within 60 days of completing their last myeloma therapy. * Subject must have an ECOG Performance Status score of 0, 1, or 2. * Subject must have the following laboratory values: * Platelet count \>=50 x 109/L (≥30 x 109 /L if myeloma involvement in the bone marrow is \> 50%) within 14 days prior to drug administration). * Absolute neutrophil count (ANC) \>= 1 x 109/L without the use of growth factors. * Corrected serum calcium \