Ixazomib and daratumumab without dexamethasone (I-Dara) in elderly frail patients with RRMM: Results of the multicenter phase 2 study (IFM 2018-02) of the Intergroupe Francophone du Myélome (IFM).

person Cyrille Touzeau University Hospital of Nantes, France, Nantes, France info_outline Cyrille Touzeau, Xavier P Leleu, Clara Mariette, Salomon Manier, Sabine Brechignac, Laure Vincent, Benjamin Hebraud, Olivier Decaux, Samantha Schulmann, Caroline Lenoir, Pascal Godmer, Agathe Farge, Laure Peyro Saint Paul, Jean-Jacques Parienti, Margaret Macro

Authors person Cyrille Touzeau University Hospital of Nantes, France, Nantes, France info_outline Cyrille Touzeau, Xavier P Leleu, Clara Mariette, Salomon Manier, Sabine Brechignac, Laure Vincent, Benjamin Hebraud, Olivier Decaux, Samantha Schulmann, Caroline Lenoir, Pascal Godmer, Agathe Farge, Laure Peyro Saint Paul, Jean-Jacques Parienti, Margaret Macro Organizations University Hospital of Nantes, France, Nantes, France, Centre Hospitalier Universitaire de Poitiers, Poitiers, France, CHU Grenoble, Grenoble, France, Lille University Hospital, Lille, France, APHP Hôpital Avicenne, Bobigny, France, Montpellier University Hospital, Montpellier, France, Cancer University Institute of Toulouse - Oncopole, Toulouse, France, University Hospital, Rennes, France, CHU Nancy, Nancy, France, Polyclinique Bordeaux Nord Nord Acquitaine, Bordeaux, France, GHBA, Vannes, France, IHBN, CHU, Caen, France, CHU, Caen, France, CHU Caen, Caen, France, University of Caen Hospital Centre, Caen, France Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Takeda and Janssen Background: Frailty is associated with inferior outcome in older myeloma patients, especially in the relapse setting. 1,2 This adverse prognosis is mainly related to a high discontinuation rate for treatment (Tx) related adverse events (AE). Dexamethasone is responsible of a high rate of infections and metabolic AE. We present here the updated results from the phase 2 study I-Dara evaluating efficacy and tolerability of Ixazomib-Daratumumab without Dexamethasone in elderly frail patients with relapsed myeloma (RRMM) (NCT03757221). Methods: Ixa-Dara naïve RRMM patients received oral Ixazomib (4 mg: days 1, 8, 15), IV Daratumumab (16 mg/kg; days 1, 8, 15, 22, cycles 1-2; days 1, 15, cycles 3-6; days 1, cycles 7+) and IV Methylprednisolone before Daratumumab (100 mg at day 1, 8, cycle 1 and then 60 mg). They were enrolled after 1 or 2 prior therapy if their frailty score was ≥ 2 by IMWG score. The primary endpoint was ≥ very good partial response rate (VGPR) at one year. Secondary endpoints included ORR, PFS, OS & toxicity according to NCI-CTCAE version 5. Results: Sixty-three patients were screened and 55 enrolled between 03/2018 and 09/2021. Patient were at first (n = 36) or second relapse (n = 19). Thirty-five patients (64%) were previously exposed to bortezomib, 37 (67%) were previously exposed to lenalidomide (Len) and 23 (42 %) were refractory to Len. Median age was 82 (72-93). All patients had a frailty score ≥2 and 13 (24 %) had a 3 or 4 frailty score. In 41 patients ISS at diagnosis was stage I (n = 11), II (n = 18) or III (n = 12). Seventeen (36%) patients harbored high-risk (HR) cytogenetic, including t(4;14) (n = 8) or del17p (n = 10). The median duration of Tx (DOT) in 14 pts with ongoing Tx was 22 mos [min-max: 16-40] at data cutoff (January, 19)]. The median DOT in 41 pts who stopped Tx was 10 mos [min-max: 0-31]: 28 had progressive disease (PD). Fourteen patients died during the study: Daratumumab-related bronchospasm (D1C1); Ixazomib-related overdose (C2), sepsis (n = 3), pneumonia (n = 2), PD (n = 7). Regarding toxicity, 31 pts had a ≥grade 3 AE (55%). The most common grade 3-4 AE were thrombocytopenia (n = 10), other cytopenias (n = 5), anemia (n = 3), infection (n = 6), gastrointestinal disorders (n = 5) and hypertension (n = 3). The ≥VGPR rate is 32 % @ 1 year (34 % overall) with an ORR of 70% @ 1 year (74 % overall). In Len refractory patients the ≥VGPR rate is 40% @ 1 y and the ORR 70 %, in HR patients the ≥VGPR rate is 60 % and ORR 80%. With a median follow-up of 23.0 mos median PFS is 18.5 mos and median OS NR (75% OS estimated at 27.9 mos). Conclusions: In this elderly frail population Ixa-Dara is a feasible combination with favorable efficacy profile even in Len refractory and HR cytogenetic patients. Early toxicity remains a concern in this population eventhough more manageable with Dara SC. Late benefit is consistent with one third of patients still on treatment. Clinical trial information: NCT03757221.

Clinical