A. , Belotti

A. , Capra

A. , Genua

A. M. , Cafro

B. , Dalla Palma

C. , Carlo-Stella

C. , Conticello

C. , Priola

F. , Patriarca

G. , Margiotta Casaluci

L. , Paris

M. , Boccadoro

M. , Cavo

M. , D’Agostino

M. T. , Petrucci

R. , Mina

R. , Rizzi

V. , Montefusco

English

Archivio istituzionale della ricerca - Università di Bari

EMN2023: April 20-22, 202332   | 2023; 7:S2P38 PATIENT-REPORTED OUTCOMES (PRO) IN RELAPSED/REFRACTORY MULTIPLE MYELOMA (RRMM) TREATED WITH MELFLUFEN AND DEXAMETHASONE (DEX) OR POMALIDOMIDE (POM) AND DEX: ANALYSES FROM THE PHASE 3 OCEAN STUDY Schjesvold F1; Ludwig H2; Delimpasi S3; Robak P4; Mateos M5; Sandberg A6; Thuresson M6; Norin S6; Richardson P7; Sonneveld P81Oslo Myeloma Center, Oslo University Hospital and KG Jebsen Center for B Cell Malignancies, University of Oslo, Oslo, Norway; 2Department of Medicine I, Center for Medical Oncology and Hematology with Outpatient Department and Palliative Care, Wilhelminen Cancer Research Institute, Vienna, Austria; 3Bone Marrow Transplantation Unit and Department of Hematology, Evangelismos Hospital, Athens, Greece; 4Department of Hemato-Oncology, University Hospital Ostrava, Ostrava, Czech Republic; 5Hospital Clínico Universitario de Salamanca/IBSAL/CIC, Salamanca, Spain; 6Oncopeptides AB, Stockholm, Sweden; 7Dana-Farber Cancer Institute, Boston, MA, USA; 8Erasmus MC Cancer Institute, Rotterdam, the NetherlandsBackground: The phase 3 OCEAN study (OP-103; NCT03151811) met its primary endpoint; melphalan flufenamide (melflufen) + dex showed superior progression-free survival vs pom+dex in patients with RRMM refractory to lenalidomide, but overall survival (second-ary endpoint) numerically favored pom+dex (Schjesvold FH, et al. Lancet Haematol. 2022;9[2]:e98-e110). Hematologic adverse events (AEs) were more frequent with melflufen+dex, but grade 3/4 infections were more common with pom+dex. Melflufen+dex was approved in Europe for the treatment of patients with ≥3 prior lines of therapy and triple—class refractory RRMM; if patients had prior autologous stem cell transplant (ASCT), time to progression (TTP) must have been >36 months.RRMM is associated with severe symptoms, of which pain, fatigue, phys-ical functioning, and emotional functioning have been strongly linked to impairments in health-related quality of life (HRQoL) for patients. Because HRQoL is known to deteriorate with each subsequent line of therapy, treatment goals should include preserving or even improv-ing HRQoL (Engelhardt M, et al. Clin Lymphoma Myeloma Leuk. 2020;21[2]:e160-e175).Objective: To evaluate functional status and well-being based on PRO assessments in patients receiving treatment with either melflufen+dex or pom+dex in the OCEAN study. Secondly, to assess PROs in the subgroup of patients with TTP >36 months after an ASCT or had no prior ASCT to understand whether results are generalizable to patients in the global target population.Methods: EORTC QLQ-C30, EORTC QLQ-MY20 and EQ-5D-3L were included in the OCEAN trial beginning with protocol version 4.1 and assessed before treatment in each cycle. Mean scores per cycle and change from baseline to cycle 6 were analyzed for Global Health Status/QoL, Physical Functioning, Emotional Functioning, Pain, Fatigue, Disease Symptoms, and Side Effects of Treatment. Within the melflufen+dex arm, the target population was compared vs the non–target population (ie, patients with TTP <36 months after an ASCT).Results: Baseline characteristics were generally well matched between patients reporting PROs (n=158) and the overall study population (N=495). Overall, mean baseline scores before treat-ment were similar between melflufen+dex and pom+dex treatment groups: 63.8 vs 64.3 in Global Health Status/QoL, 72.4 vs 74.2 in Physical Functioning, 81.0 vs 79.8 in Emotional Functioning, 35.1 vs 32.6 in Fatigue, 30.2 vs 28.7 in Pain, 24.7 vs 22.6 in Disease Symptoms, 16.1 vs 16.1 in Side Effects of Treatment, and 64.0 vs 66.9 for the EQ-5D-3L VAS, respectively. Mean scores remained generally constant between baseline and follow-up timepoints (Figure). Mean baseline scores before treatment with melflufen+-dex were similar between the target population and the non–tar-get population groups: 65.3 vs 61.9 in Global Health Status/QoL, 73.2 vs 71.5 in Physical Functioning, 83.3 vs 78.0 in Emotional Functioning, 30.7 vs 40.7 in Fatigue, 26.2 vs 35.4 in Pain, 23.0 vs 27.1 in Disease Symptoms, 15.9 vs 16.3 in Side Effects of Treatment, and 64.8 vs 62.8 for the EQ-5D-3L VAS, respectively. Despite small patient numbers (n=44), the target population group showed a sim-ilar trend to that of the overall population.Conclusion: Given the negative impact of treatment-related AEs on HRQoL in RRMM, results from OCEAN are encouraging. HRQoL was maintained throughout treatment with melflufen+dex, including in the target population, and was similar to that with pom+dex.P39 DEDALO: PHASE II STUDY OF DARATUMUMAB PLUS POMALIDOMIDE AND DEXAMETHASONE (DPD) IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA AND 17P DELETION Montefusco V.1; Cafro A.M.1; Margiotta Casaluci G.2; Patriarca F.3;  Mina R.4; D’Agostino M.4; Capra A.4; Priola C.4; Dalla Palma B.5;  Rizzi R.6; Genua A.7; Petrucci M.T.8; Paris L.9; Belotti A.10; Cavo M.11; Conticello C.12; Carlo-Stella C.13; Boccadoro M41European Myeloma Network (EMN) Italy, Milan, Italy; 2Pavia, Italy; 3Udine, Italy; 4Torino, Italy; 5Parma, Italy; 6Bari, Italy; 7Terni, Italy; 8Roma, Italy; 9Bergamo, Italy; 10Brescia, Italy; 11Bologna, Italy; 12Catania, Italy; 13Rozzano, ItalyIntroduction: Deletion of the short arm of chromosome 17 (del(17p)) is a well-established high-risk feature in multiple myeloma (MM) and is included in current disease staging criteria. Treatment of del(17p) MM is a major challenge due to rapid development of chemoresistance and short survival. The size of del(17p) clone correlates with prognosis, and the 55-60% threshold has the worst prognosis. Approximately 1/3 of pts have a concomitant TP53 mutation, with a complete abolition of the protein function. TP53 biallelic inactivation is defined as double-hit myeloma.Pomalidomide-dexamethasone showed promising results in this setting (Leleu et al, Blood 2014). Daratumumab is an attractive strategy for treatment of MM pts with del(17p).In the phase II DEDALO trial (NCT04124497), we assessed daratumum-ab-pomalidomide-dexamethasone (DPd) in RRMM pts with del(17p).Methods: Key eligibility criteria included: RRMM; up to 3 prior lines of therapy, del(17p) observed by FISH in at least 10% of plasma cells at any time of MM history, previous exposure to lenalidomide, no refrac-toriness or intolerance to pomalidomide, nor previous exposure to an anti-CD38 monoclonal antibody.Continuous DPd treatment consisted of daratumumab (1800 mg sub-cutaneously or 16 mg/kg intravenously) weekly during cycles 1 and 2, every 2 weeks during cycles 3–6, and every 4 weeks thereafter; oral pomalidomide (4 mg, once daily on days 1–21); and oral or intravenous dexamethasone (40 mg once daily on days 1, 8, 15, and 22; 20 mg for pts ≥75 years) at each 28-day cycle. The primary endpoint was MRD 10-5 negativity within the first 12 months of treatment. NGF and NGS MRD analyses were performed. The key secondary endpoints were PFS, ORR and OS.Results: Forty-five pts were enrolled. The median age was 63 (range 43-83) years (yrs), and 60%/29%/11% of pts had ISS stage I/II/III. All pts had >10% del(17p) and 14 pts had ≥55% del(17p); t(4;14) was observed in 6, t(14;16) in 6, del(1p) in 10, and 1q+ in 16 pts. Median number of prior lines of therapy was 1 (range 1-3); 100% had been previously exposed to lenalidomide and 86% to a proteasome inhibitor.Three pts achieved MRD negativity by NGF, while NGS analysis is ongoing. ORR was 60%, including 13 pts with PR, 12 with VGPR, and 2 with ≥CR. Median time-to-response was 2.5 months. With a median follow-up of 8.5 months (range 6.3-13.9), median PFS was 7.1 months (range 5.9 – not reached [NR]; Figure).By subgroup analysis, PFS was: 8.4 months in pts with del(17p) clone size <60% and 6.5 months in pts with del(17p) clone size ≥60% (HR, 0.75; 95% CI 0.33-1.7; P=0.48); 12.4 months in pts with ISS I vs 4.2 months in pts with ISS II-III (HR, 2.48; 95% CI 1.12-5.51; P=0.02); 6.6 months in pts at first relapse vs 7.1 months beyond first relapse (HR 0.95; 95% CI 0.42-2.12; P=0.89); 7.1 months in pts <65 yrs and 7.6 months in those ≥65 yrs of age (HR 0.84; 95% CI 0.37-1.92; P=0.68). Median OS was NR. No new safety concerns were observed. TP53 mutational analysis is underway.Downloaded from http://journals.lww.com/hemasphere by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdgGj2MwlZLeI= on 07/30/2023EMN2023: April 20-22, 2023 | 2023; 7:S2 33Conclusion: In this difficult-to-treat population, DPd is a thera-peutic option for pts of all ages and can be considered as a bridge to other immunotherapies, such as T-cell engagers and CAR-T cells.P40 REAL-WORLD TREATMENT PATTERNS OF PATIENTS INITIATING THIRD-LINE THERAPY IN RELAPSED/REFRACTORY MULTIPLE MYELOMA IN EUROPE Lehne M.1; Kortüm K.M.2; Zamagni E.3; d’Estrube T.4; Shukla S.5; Zhuleku E.1; Ghiani M.6; Hanna M.5; Maywald U.7; Wilke T.6;  Perera S.4¹Cytel Inc., Berlin, Denmark; 2Universitätsklinikum Würzburg, Würzburg, Denmark; 3Universita di Bologna, Bologna, Italy; 4GSK, London, United Kingdom; 5GSK, Upper Providence, PA, USA; 6Institut für Pharmakoökonomie und Arzneimittellogistik e.V., Wismar, Denmark; 7AOK PLUS, Dresden, DenmarkObjectives: Real-world (RW) evidence can provide valuable insights into clinical practice and help identify and address unmet medical needs. We report RW treatment utilisation in patients from European data sets who initiated third-line (3L) treatment for relapsed/refractory multiple myeloma (RRMM).Methods: This retrospective, noninterventional analysis used claims data from the German AOK PLUS health insurance fund and Italian Local Health Units (2012–2020). Patients initiating 3L treatment from 2016–2020 (index) were identified using an algorithm based on prescription and procedure codes. New lines of treatment were defined as introduction of a new agent not part of the prior line. Agents given ≤30 days of start of the line defined the regimen. Retreatments after >6 months of discontinuation were considered a new line. Baseline characteristics and treatment patterns were reported.Results: Patients were identified from Germany (N=276) and Italy (N=289) (Table). Baseline characteristics were similar between countries. Prior to 3L treatment, immunomodulatory imide drug (IMiD) use was higher (74% vs 56%) and proteasome inhibitor (PI) use was lower (52% vs 96%) among patients in Italy versus Germany. At 3L, the proportion of double-class exposed patients in Italy was lower versus Germany (33% vs 52%).In Germany, common first-line (1L) regimens were bortezomib (BORT) + dexamethasone (DEX; Vd, 46%), BORT + melphalan (MEL) + pred-nisone (PRED; VMP, 14%), and Vd + cyclophosphamide (CyBORD, 8%). The most common second-line (2L) treatment regimens were lenalidomide (LEN) + DEX (Rd, 30%), Vd (11%), and carfilzomib (CFZ) + Rd (KRd, 8%). By 3L, 95% and 54% of patients had received prior BORT- and LEN-based regimens, respectively. In 3L, combina-tions were often LEN- and/or CFZ-based with daratumumab (DARA) monotherapy and pomalidomide + DEX (Pd) also contributing ~4% each (Table).Table Baseline (12 months) and treatment characteristics in patients with relapsed/refractory multiple myeloma who initiated 3L treatmentCharacteristic Germany (N=276) Italy (N=289) Male, n (%) 139 (50) 141 (49)Median age at index (interquartile range), years 75 (65–80) 73 (66–79)Median time since diagnosis (range), years 2.7 (0.4–7.4) 2.1 (0.3–6.7)Year of 3L treatment initiation, n (%)     2016 58 (21) 35 (12)  2017 57 (21) 48 (17)  2018 57 (21) 52 (18)  2019 54 (20) 80 (28)  2020 50 (18) 74 (26)Prior treatment (excluding maintenance), n (%)     PI 264 (96) 151 (52)  Immunomodulatory drug 154 (56) 213 (74)  anti-CD38 30 (11) 13 (4.5)  LEN + PI-exposed and POM-naive 135 (49) 61 (21)  Double-class exposed 144 (52) 96 (33)  Triple-class exposed 15 (5) 8 (3)  Stem cell transplant 75 (27) 43 (15)3L treatment regimens ≥4% in either country, n (%)     Rd 53 (19) 79 (27)  KRd 27 (10) 11 (4)  Kd 22 (8) 9 (3)  DRd 22(8) 15 (5)  DVd 18 (7) ≤3a  Pd 11 (4) 35 (12)  DARA 11 (4) 0 (0)  Melphalan + prednisone 0 (0) 21 (7)aNot issuable due to anonymisation regulations.Rd, LEN + DEX; KRd, CFZ + LEN + DEX; Kd, CFZ + DEX; DRd, DARA + LEN + DEX; DVd, DARA + BORT + DEX; Pd, POM + DEX.3L, third-line; BORT, bortezomib; CFZ, carfilzomib; DARA, daratumumab; DEX, dexamethasone; LEN, lenalidomide; PI, proteasome inhibitor; POM, pomalidomide.In Italy, common 1L regimens included MEL ± DEX ± PRED (22%), Vd (6%), and thalidomide (THAL) + DEX (5%). Rd (40%) and Vd (8%) were the most common 2L regimens; by 3L, 56% and 49% of patients had received prior LEN- and BORT-containing regimens, respectively.Overall, use of Pd in 3L in Italy was higher than in Germany (12% vs 4%), whereas use of CFZ- (10% vs 21%) and DARA-based (9% vs 29%) regimens was lower. In 3L, use of conventional therapies, such as MEL (15% vs 3%), was higher in Italy versus Germany.Retreatment patterns in Germany and Italy showed that 60% and 82% of patients initiating 3L treatment, respectively, had prior exposure to the same agent class (IMiD, PI, monoclonal antibodies). Of 50 patients in Germany receiving BORT in 3L, 47 (94%) had prior BORT; of 135 patients receiving LEN in 3L, 47 (35%) had prior LEN. Of 40 patients in Italy receiving BORT in 3L, 31 (78%) had prior BORT; of 131 patients receiving LEN in 3L, 82 (63%) had prior LEN. Additionally, of 13 patients in Italy who received prior THAL, all were retreated with THAL in 3L.Conclusions: This study provides a perspective of RW clinical practice from 2012-2020 for comparison with the evolving treatment landscape for RRMM.P41 NO EVIDENCE OF B-CELL MATURATION ANTIGEN (BCMA) EXPRESSION LOSS OR SYSTEMIC IMMUNE IMPAIRMENT AFTER TREATMENT WITH THE BCMA-TARGETED ANTIBODY-DRUG CONJUGATE BELANTAMAB MAFODOTIN IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA Lowther D.E.1; Houseman E.A.2; Han G.2; Kleanthous E.1;  Knoblock D.2; Zhou X.2; Banerjee S.3; Patel S.2; Figueroa D.21GSK, Stevenage, United Kingdom; 2GSK, Upper Providence, PA, USA; 3GSK, Bengaluru, IndiaObjectives: Belantamab mafodotin (belamaf)—an antibody-drug conjugate targeting B-cell maturation antigen (BCMA)—demonstrated deep and dura-ble responses in the DREAMM-2 trial of patients with relapsed/refractory Downloaded from http://journals.lww.com/hemasphere by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdgGj2MwlZLeI= on 07/30/2023

DEDALO: PHASE II STUDY OF DARATUMUMAB PLUS POMALIDOMIDE AND DEXAMETHASONE (DPD) IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA AND 17P DELETION

https://ricerca.uniba.it/bitstream/11586/440520/1/P39_DEDALO__PHASE_II_STUDY_OF_DARATUMUMAB_PLUS.58.pdf

DEDALO: PHASE II STUDY OF DARATUMUMAB PLUS POMALIDOMIDE AND DEXAMETHASONE (DPD) IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA AND 17P DELETION

Abstract

Similar works

Full text

Available Versions

Archivio istituzionale della ricerca - Università di Bari