Clinical Lymphoma, Myeloma & Leukemia, Vol.21, Suppl.1 - September 2021

Abstracts Clinical Lymphoma, Myeloma & Leukemia September 2021 S424 Cambridge, MA, USA, 16 Sanofi Oncology Development, Vitry-Sur- Seine, France Backgrou n d: Isa is an approved monoclonal antibody that binds to a specific epitope on the CD38 receptor. Phase 3 ICARIA- MM study (NCT02990338) demonstrated improved progression- free survival (PFS) with Isa-Pd vs Pd (P=0.001) and manageable safety profile. Here, we report updated ICARIA results. Methods: Patients with RRMM (N=30 7 ) who received  2 prior therapies, including lenalidomide (Len) and a proteasome inhibitor (PI), were randomized to Isa-Pd (n=154) or Pd (n=153). Isa was administered intravenously at 10 mg/kg weekly for 4 weeks and every other week thereafter. This pre-planned second interim analysis assessed time to next treatment (TTNT), overall survival (OS), time from randomization to disease progression on first subsequent therapy or death (PFS2), and safety. Results: Patients had median 3 prior lines of therapy. As of Oct 1, 2020 (median follow-up, 35.3 months), 2 7 Isa-Pd patients (18%) vs 12 Pd patients (8%) were still on treatment; 60% vs 7 2% proceeded to subsequent therapy. Median TTNT: 15.5 months Isa-Pd vs 8.9 months Pd (HR 0.56; 95% CI 0.42–0. 7 4; P<0.0001); 24% vs 58% of patients with subsequent therapy received daratumumab. Overall response rate (ORR) in subsequent treatment with daratumumab monotherapy was lower in Isa-Pd vs Pd (14% vs 38%) but similar (31% vs 32%) with daratumumab combination therapy (+immunomodulator, +alkylator, +PI). Median PFS2 in ITT: 1 7 .5 months Isa-Pd vs 12.9 months Pd (HR 0. 7 6; 95% CI 0.58–0.99; P=0.0202). Median OS: 24.6 months Isa-Pd vs 1 7 . 7 months Pd (HR 0. 7 6; 95% CI 0.58–1.01; one-sided P=0.0280). Median treatment duration: 4 7 .6 weeks (1.3–1 7 1.6) Isa-Pd vs 24.0 weeks (1.0–168.6) Pd. Serious treatment-emergent adverse event (TEAEs): 7 3% Isa-Pd vs 60% Pd. Most frequent non-hematologic TEAEs (any grade) with Isa-Pd: infusion reaction (38%), URTI (34%), diarrhea (30%). Grade 3–4 neutropenia (85% vs 7 1%) and thrombocytopenia (34% vs 25%) were more frequent with Isa- Pd. Co n clusio n s: Isa-Pd demonstrates significant improvement in TTNT and PFS2 vs Pd. A strong trend in OS benefit was seen in the Isa-Pd arm, with approximately 7 months improvement in median OS. The OS profile remains unchanged from prior analyses. Keywords: MM, isatuximab, pomalidomide, ICARIA, CD38, relapsed and refractory multiple myeloma MM-146 A Real-World Study of Bendamustine Therapy in a Very Heavily Pre-Treated Population of Multiple Myeloma Patients Sarah Bird 1,2 *, Akaterina Panopoulou 1,2 , Martin Kaiser 1,2 , Kevin Boyd 1,2 , Charlotte Pawlyn 1,2 1 The Royal Marsden Hospital NHS Foundation Trust, London, UK, 2 The Institute of Cancer Research, London, UK Co n text: Bendamustine is an alkylating agent with activity against multiple myeloma (MM), and in UK clinical practice, its use is predominately limited to patients who have no other therapeutic options. Objecti v e: Assessment of efficacy and toxicity of bendamustine in the real-world setting. D esig n : Retrospective case-review study including patients commenced on bendamustine Jan. 2016–Jan. 2021 (follow-up until May 2021). Setti n g: A UK tertiary MM center. Patie n ts: Twenty-nine patients received bendamustine and corticosteroids, 14 in combination with thalidomide, with a median of 5 prior lines of therapy. Cytogenetic data were available in 19; 95% (18/19) had high-risk-disease at their most recent assessment prior to commencing bendamustine. I n ter v e n tio n s: Bendamustine was given at 60 mg/m 2 D1,2; dexamethasone/methylprednisolone weekly; thalidomide 50– 200mg daily (28-day cycle). Mai n Outco m es Measures: Overall response rate (ORR,  partial response, PR), clinical benefit rate (CBR,  minimal response, MR), progression-free survival (PFS), overall survival (OS), and toxicity. Results: The median PFS of the cohort was 1.8 months (median follow-up 13 months), and the OS was 4.8 months. Of the 29 patients, 23 were assessable for response (4 completed <1 cycle, 2 had a secretory disease). The ORR was 26% (6/23, all PR), and the CBR was 39% (9/23). Achievement of  PR was associated with longer PFS and OS (median PFS 5.3 months vs 1.8 months, p=0.10; OS 14 months vs 4.1 months, p=0.15). Toxicity assessment was performed in the whole cohort. Twenty-eight percent (8/29) had received  5 cycles at time of data cut-off and 3 remain on treatment. The reason for stopping therapy was progression in 65% (1 7 /26) and death in 23% (6/26). One patient stopped treatment due to significant cytopenias, 1 due to frailty, and 1 because bendamustine had been used as a bridge to alternative therapy. Thirty-four percent (10/29) only completed  1 cycle of therapy, 3 died, 6 progressed, and 1 had severe cytopenias. Fifty-five percent (16/29) required transfusion of platelets and/or red blood cells during their treatment. Co n clusio n s: In this very heavily pre-treated population, bendamustine was associated with an ORR of 26%, and the overall PFS and OS were short at 1.8 and 4.8 months, respectively. However, achieving  PR was associated with a longer PFS and OS (5.3 and 14 months, respectively), suggesting bendamustine may provide a therapeutic option for a subgroup of patients when no others are available. Keywords: MM, multiple myeloma, relapsed, refractory, bendamustine MM-155 Phase 3 MAIA Study: Overall Survival (OS) Results with Daratumumab, Lenalidomide, and Dexamethasone (D- Rd) vs Lenalidomide and Dexamethasone (Rd) in Patients with Transplant-Ineligible Newly Diagnosed Multiple Myeloma (TIE-NDMM) Robert Orlowski 1 *, Thierry Facon 2 , Shaji Kumar 3 , Torben Plesner 4 , Philippe Moreau 5 , Nizar Bahlis 6 , Supratik Basu 7 , Hareth Nahi 8 , Cyrille Hulin 9 , Hang Quach 10 , Hartmut Goldschmidt 11 , Michael O’Dwyer 12 , Aurore Perrot 13 , Christopher Venner 14 , Katja Weisel 15 , Joseph Mace 16 , Noopur Raje 17 , Mourad Tiab 18 , Margaret Macro 19 ,