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3361 Isatuximab in Combination with Bortezomib, Cyclophosphamide, and Dexamethasone, Followed By Isatuximab and Lenalidomide Maintenance in Newly Diagnosed Patients with Multiple Myeloma and Severe Renal Impairment: A Phase 2 Study of the Greek Myeloma Study Group

Program: Oral and Poster Abstracts
Session: 654. Multiple Myeloma: Pharmacologic Therapies: Poster II
Hematology Disease Topics & Pathways:
Research, Clinical trials, Combination therapy, Clinical Research, Plasma Cell Disorders, Diseases, Treatment Considerations, Biological therapies, Lymphoid Malignancies
Sunday, December 8, 2024, 6:00 PM-8:00 PM

Evangelos Terpos, MD, PhD1, Efstathios Kastritis, MD1*, Sosana Delimpasi, MD2*, Maria Kotsopoulou, MD3*, Konstantina Papathanasiou, MD4*, Vasiliki Labropoulou, MD5*, Eirini Katodrytou6*, Ioannis Ntanasis-Stathopoulos, MD, PhD, MSc1*, Panagiotis Malandrakis, MD1*, Despina Fotiou, MD1*, Magdalini Migkou, MD1*, Foteini Theodorakakou, MD1*, Vasiliki Spiliopoulou, MD1*, Nikolaos Kanellias1*, Evangelos Eleutherakis-Papaiakovou, MD1*, Giorgos Psarros, MSc7*, Maria Gavriatopoulou1* and Meletios Dimopoulos, MD1

1Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece
2Department of Hematology and Bone Marrow Transplantation Unit, Evangelismos Hospital, Athens, Greece
3Department of Hematology, Metaxa Cancer Hospital, Piraeus, Greece
4Department of Hematology, Faculty of Medicine, University of Ioannina, Ioannina, Greece
5Hematology Division, Department of Internal Medicine, University of Patras, Medical School, Patras, Greece
6Department of Hematology, Theagenio Cancer Hospital, Thessaloniki, Greece
7Health Data Specialists, Dublin, Ireland

Introduction

Renal impairment (RI) is a frequent complication of multiple myeloma (MM) associated with poor prognosis. Reversing MM-related RI is crucial for improving survival. Bortezomib/dexamethasone (Vd)-based regimens are essential for newly diagnosed MM (NDMM) patients (pts) with severe RI, including those requiring dialysis. Phase 3 studies (ICARIA-MM and IKEMA) showed adding Isatuximab (Isa) to standard treatment regimens improves and sustains renal responses in relapsed/refractory MM (RRMM) pts with moderate RI. In NDMM, a phase 1b study indicated Isa with Vd and cyclophosphamide (Isa-VCd) has substantial anti-myeloma effects even in pts with RI. Here, we report preliminary results from the EAE116 study, which investigates the effect of Isa-VCd as induction treatment on the renal function of NDMM pts with severe RI and its anti-myeloma effects when followed by maintenance with Isa plus lenalidomide (Len).

Methods

EAE116 (NCT05147493) is an investigator-initiated, phase 2, prospective, open-label, multicenter study currently underway in Greece, aiming to enroll 51 adult NDMM pts with severe RI, defined as estimated glomerular filtration rate [eGFR] <30 ml/min/1.73m2 or requiring dialysis. Patients must also have sufficient bone marrow and liver function and an Eastern Cooperative Oncology Group performance status (ECOG PS) of 2 or less. Pts with prior/current systemic therapy or stem cell transplantation for any plasma cell dyscrasia are excluded. Pts receive six 28-day cycles of Isa-VCd as induction treatment (Isa 10 mg/kg IV [Cycle 1: D1, 8, 15, 22; Cycles 2-6: D1, 15]; bortezomib 1.3 mg/m2 SC [Cycle 1: D1, 4, 8, 11; Cycles 2-6: D1, 8, 15, 22]; cyclophosphamide 300 mg/m2 IV [Cycle 1: D1, 8, 15; Cycles 2-6: D1, 8, 15, 22]; and dexamethasone 40 mg (or 20 mg for pts ≥75 years of age) PO or IV [Cycle 1: D1, 2, 3, 4, 9, 10, 11, 12; Cycles 2-6: D1, 8, 15, 22]) and thereafter (Cycle 7 onwards) IsaLen as maintenance treatment (Isa 10 mg/kg IV [D1 of each cycle]; Len 10 mg PO [or according to renal function] daily [D1-28 of each cycle]) until disease progression, death, or unacceptable toxicity. The primary endpoint is the renal response rate (RRR) after six months of treatment with Isa-VCd as per the International Myeloma Working Group (IMWG) criteria.

Results

As of 31 May 2024 (data cut-off), 50 pts had received ≥1 dose of Isa-VCd and thus are included in this analysis, of which 37 (74.0%) were still on treatment and 13 (26.0%) had discontinued due to death (7 pts [14.0%]), progressive disease (2 pts [4.0%]), consent withdrawal (2 pts [4.0%]) or physician’s decision (2 pts [4.0%]). Median age at baseline was 70.0 years (range 46.0-89.0), with 31 (62.0%) pts being male and 44 (88.0%) having ECOG PS ≤1. Twenty-six (52.0%) pts had stage II and 24 (48.0%) stage III disease as per the revised International Staging System (R-IIS), 7 (14.0%) had high-risk cytogenetics, 14 (28.0%) had lytic bone lesions and 6 (12.0%) had soft-tissue plasmacytomas. Additionally, 11 (22.0%) pts required dialysis. At a median follow-up of 8.5 months (range <0.1-21.2), pts had received a median of 8.0 cycles (range 1.0-23.0). The overall renal response rate (minor response or better) among evaluable pts (44 pts) was 68.2%, with 14 (31.8%) pts achieving PR or better (RRR) and median time to first renal response of 1.2 months (range 0.9-6.1). Among those evaluable for myeloma response (47 pts), the ORR was 83.0% with 57.4% achieving ≥very good partial response (VGPR). The median time to first myeloma response was 1.0 month (range 0.9-11.1). Thirty-seven (74.0%) pts experienced ≥1 treatment-emergent AE (TEAE) and 15 (30.0%) pts ≥1 serious TEAE. Grade ≥3 TEAEs were reported in 18 (36.0%) pts. Most common (≥5%) Gr≥3 TEAEs were pneumonia (8%) and urinary tract infection (6%). Fatal SAEs were observed in 7 pts (14%) and corresponded to respiratory tract infection (2 pts), septic shock (2 pts), pneumonia (1 pt), respiratory failure (1 pt) and aortic aneurysm rupture (1 pt).

Conclusion

Induction treatment with Isa-VCd elicits promising myeloma responses in NDMM pts with severe RI. The safety profile is consistent with that of the individual drugs. Infections were the most common Gr≥3 TEAE, which is an expected safety finding in this frail population. We conclude that Isa-VCd may be a new option for NDMM with severe RI.

Disclosures: Terpos: Amgen: Honoraria, Other: Travel expenses, Research Funding; BMS: Honoraria; AstraZeneca: Honoraria, Other: Travel expenses; EUSA Pharma: Honoraria, Other: Travel expenses; GSK: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Menarini/Stemline: Honoraria; Pfizer: Honoraria; Sanofi: Honoraria, Other: Travel expenses, Research Funding; Takeda: Honoraria, Other: Travel expenses, Research Funding; Novartis: Honoraria; Antengene: Honoraria, Research Funding; Swixx: Honoraria. Kastritis: Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Honoraria; Amgen: Honoraria; Genesis Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Prothena: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Delimpasi: GSK: Honoraria; Janssen: Honoraria; Takeda: Honoraria; Amgen: Honoraria. Kotsopoulou: BMS: Honoraria; Abbvie: Honoraria; Amgen: Honoraria; GENESIS PHARMA: Honoraria; GSK: Honoraria, Research Funding; GILEAD SCIENCES: Honoraria; INTEGRIS: Honoraria; Janssen: Honoraria; Novartis: Honoraria; Roche: Honoraria; Sanofi: Honoraria, Research Funding; Vianex: Honoraria; Winmedica: Honoraria. Labropoulou: Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Demo: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Genesis Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Johnson and Johnson: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; WinMedica: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Vianex: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Ntanasis-Stathopoulos: AstraZeneca: Honoraria; Cellectar Biosciences: Research Funding; Janssen-Cilag: Honoraria. Fotiou: Sanofi: Honoraria; Janssen: Honoraria. Migkou: GlaxoSmithKline: Honoraria; Janssen Cilag: Honoraria. Psarros: Health Data Specialists: Current Employment. Gavriatopoulou: Amgen: Consultancy; Beigene: Research Funding; AbbVie: Honoraria; BMS: Research Funding; Cellectar Biosciences: Research Funding; GSK: Consultancy, Honoraria; Integris: Honoraria; Takeda: Consultancy, Honoraria; Swixx: Honoraria; Janssen Cilag: Honoraria; Karyopharm: Consultancy; Genesis Pharma: Honoraria. Dimopoulos: AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consulting fee; Regeneron: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consulting fee; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consulting fee; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consulting fee; Menarini: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consulting fee; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consulting fee; BeiGene Inc: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consulting fee; Amgen, Abbvie, Takeda, Beigene, BMS, GSK, Janssen, Menarini, Regeneron, Sanofi: Other: Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events; Swixx: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consulting fee; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees.

*signifies non-member of ASH