2018 ASCO Annual Meeting!
Session: Hematologic Malignancies—Plasma Cell Dyscrasia
Type: Poster Session
Time: Monday June 4, 8:00 AM to 11:30 AM
Location: Hall A
Final results of a phase Ib study of isatuximab (ISA) plus pomalidomide (Pom) and dexamethasone (dex) in relapsed/refractory multiple myeloma (RRMM).
Hematologic Malignancies—Plasma Cell Dyscrasia
2018 ASCO Annual Meeting
Poster Board Number:
Poster Session (Board #47)
J Clin Oncol 36, 2018 (suppl; abstr 8038)
Author(s): Joseph Mikhael, Paul G. Richardson, Saad Zafar Usmani, Noopur S. Raje, William Bensinger, Franck Dubin, Qianying Liu, Olivier Vitse, Kenneth Carl Anderson; Mayo Clinic, Phoenix, AZ; Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA; Levine Cancer Institute/Carolinas Healthcare System, Charlotte, NC; Massachusetts General Hospital Cancer Center, Boston, MA; Swedish Cancer Institute, Seattle, WA; Sanofi, Vitry-Sur-Seine, France; Sanofi Onology, Cambridge, MA; Sanofi, Montpellier, France; Dana-Farber Cancer Institute, Boston, MA
Background: ISA is a monoclonal antibody targeting CD38-expressing tumor cells. We report final data from a Ph Ib dose-escalation/expansion study of ISA + Pom/dex in pts with RRMM (NCT02283775). Methods: Pts with RRMM (≥2 prior MM therapies; includes lenalidomide + a proteasome inhibitor [PI]) received 5, 10, or 20 mg/kg ISA (4 weekly [QW] doses, then every 2 wks until progression/intolerable toxicity), Pom 4 mg (Days 1–21), and dex 40 mg (QW; 20 mg if ≥75 yrs old) in 28-day cycles. Primary objective: recommended dose of ISA + Pom/dex. Secondary objectives included efficacy (IMWG criteria), safety, pharmacokinetics (PK). Results: 45 pts received ISA at 5 (n = 8), 10 (n = 31), or 20 (n = 6) mg/kg. Median age 67 (42–82) yrs. Median 3 (2–10) prior lines; 41 (91%), 37 (82%), and 38 (84%) pts refractory to their last regimen, immunomodulatory drugs (IMiDs), or PIs, respectively. 6 pts had high-risk (HR) cytogenetics. Median treatment time: 9.6 mos; 19 (42%) pts remain on treatment. 2 pts (10 mg/kg) discontinued due to AEs (grade [Gr] 5 intestinal perforation [due to underlying MM]; Gr 3 infusion-associated reaction [IAR]). 1 pt at each dose reported a DLT; MTD not reached. Expansion cohort initiated at 10 mg/kg based on efficacy, safety, and PK data. Most common TEAEs, besides IARs/hematologic AEs: fatigue (62%), upper respiratory tract infection (42%), and dyspnea (40%). Gr ≥3 neutropenia occurred in 83% of pts (Gr 4, 56%); all cases reported as AEs resolved with dose modification/growth factor support. IARs occurred in 19 (42%) pts (Gr ≥3, 1 pt): 18 (40%) pts during 1st infusion, 3 (7%) pts at later infusions. Overall response rate (ORR) was 62%; ORR in HR cytogenetics: 33%; IMiD refractory: 57%; PI refractory: 63%. 12 (27%) pts achieved ≥ VGPR (1 CR; 1 sCR). Median time to 1st response, 0.95 mos; median duration of response, 18.7 mos (95% CI 12.5–NC). Median progression-free survival, 17.6 mos (95% CI 6.8–20.5). ISA PK is unaffected by Pom/dex co-administration. Conclusions: These final results confirm the promising clinical activity and manageable safety profile of ISA + Pom/dex in heavily pretreated RRMM. A Ph III confirmatory trial is ongoing with results expected later in 2018. Funding: Sanofi Clinical trial information: NCT02283775
2. Pomalidomide (POM), bortezomib, and low‐dose dexamethasone (PVd) vs bortezomib and low-dose dexamethasone (Vd) in lenalidomide (LEN)-exposed patients (pts) with relapsed or refractory multiple myeloma (RRMM): Phase 3 OPTIMISMM trial.