PB2132 DARATUMUMAB MONOTHERAPY FOR RELAPSED AND REFRACTORY MULTIPLE MYELOMA REAL CLINICAL PRACTICE. A MULTICENTRIC RETROSPECTIVE STUDY
Authors: Vizcaya A. Lorenzo , Álvarez J. Vázquez , Barrigón F. Escalante , Rodríguez M. A. Bermúdez , Ferro R. Ferreiro , Player Á. Ramírez , García M. E. González , Sánchez J. Á. Méndez , Gómez J. Labrador , Señarís D. Martínez , Loureiro A. M. Dios , Alameda F. Taboada , Rubira E. Lavilla 
Published: June 2019

Background:Daratumumab (DARA) was first approved as monotherapy for patients (P) with relapsed and refractory (RR) multiple myeloma (MM) after treatment with immunomodulatory drugs and proteasome inhibitors, and who have progressed on the last therapy, based on data from the phase 2 SIRIUS trial. Its results show 29% of P with at least partial response, progression‐free survival (Sv) (PFS) of 3.7 months(m) and overall survival (OS) of 17.5 m, and acceptable toxicity.Aims:So far, there are scarce data on treatment with DARA monotherapy in routine clinical practice.MethodsObservational, retrospective and multicenter study of P with RRMM treated with DARA in monotherapy outside clinical trial (CT) in various Spanish regions: Galicia, Asturias, Cantabria y Castilla y León. Statistical descriptive analysis with SPSS®: Sv curves by Kaplan‐Meier and measures of statistical association using Chi2.Results:There were 80 P (61% males) evaluable. Characteristics at diagnosis: age 64.8 years (y) (IQR 57.1‐73.3); previous COPD/asthma: 11.25%; myeloma stage ISS 3: 37.5%, and 2: 31.25%; adverse cytogenetics (del17p, t(4;14), t(14;16)): 21.25%. Characteristics at starting of DARA: age 70.5 y (IQR 60.9‐76.1); adverse cytogenetics: 17/33 P (52.5%); previous lines of treatment: median 3 (1‐10), in 52.5% of P including carfilzomib and/or pomalidomide; previous ASCT: 51.25%.The median of DARA doses administered per patient were 10 (1‐26); it should be pointed out tha t5 P only received 1 dose. The majority (78.7%) received the 1st dose hospitalized, and in 38.7% montelukast was associated to the conventional premedication. The rate of infusion‐ related reactions (IRR) is 23.7% for the 1st dose (grade 1: 78.9%, grade 3: 15.8%), with no difference according to premedication. Only 3 P suffered IRR grade 1 after 2nd dose.Response. Overall R (OR) 66.6% (CR 13.3%, PR + VGPR 33.3%, MR/SD 20%), progression 33.3%. With a median follow‐up of 243 days (IQR 113‐392), 48.7% have died (cause of death 79.4% MM) with no toxic mortality, and 25% continue treatment. PFS and OS are 111 days (87‐252) and 280 days (173‐700), respectively.Adverse events. Any grade adverse events occurred in 38.7%, being the most frequent neutropenia and/or infection (52%), thrombocytopenia (26%), nausea/vomiting (10%) and peripheral neuropathy (4%). All grade 3 (34%), and 4 (18%) adverse events were due to myelotoxicity and infection. In 25% of P a dose of DARA was delayed, for an average of 11 days (2‐30), 55% of them due to infection. None had to discontinue DARA because of toxicity.Summary/Conclusion:Our experience outside clinical trials confirms that DARA monotherapy is a safe and well‐tolerated drug, even in this population of elderly P with advanced disease and multiple previous lines of therapy. There are no serious IRR and the main toxicity, as otherwise should be expected, has been myelosuppression and infections. The OR rate is high, highlighting 46.6% with at least PR, but in spite of this PFS and OS are short, 3.7 m and 9.3 m respectively; in special OS is much lower than previously referred in SIRIUS trial. It should be noted out that 17 P did not complete the 1st cycle of DARA (4 doses) and 5P received only 1 dose, so a better selection of candidates for this Trt will probably improve these results.