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1991 Isatuximab in Combination with Pomalidomide and Dexamethasone in RRMM Patients with One Prior Line of Lenalidomide-Containing Therapy: A Phase 2 Study of the Greek Myeloma Study Group

Program: Oral and Poster Abstracts
Session: 654. Multiple Myeloma: Pharmacologic Therapies: Poster I
Hematology Disease Topics & Pathways:
Research, Clinical trials, Combination therapy, Clinical Research, Plasma Cell Disorders, Diseases, Treatment Considerations, Biological therapies, Lymphoid Malignancies
Saturday, December 7, 2024, 5:30 PM-7:30 PM

Evangelos Terpos, MD, PhD1, Maria Gavriatopoulou1*, Alexandros Spyridonidis, MD, PhD2*, Emmanouil Spanoudakis, MD, PhD3*, Anastasia Sioni, MD4*, Eirini Katodrytou5*, Eleftheria Hatzimichael, MD, PhD6*, Maria Kotsopoulou, MD7*, Nikolaos Giannakoulas, MD, PhD8*, Ioannis Ntanasis-Stathopoulos, MD, PhD, MSc1*, Panagiotis Malandrakis, MD1*, Despina Fotiou, MD1*, Magdalini Migkou, MD1*, Foteini Theodorakakou, MD1*, Vasiliki Spiliopoulou, MD1*, Nasia Antoniou, MSc, PhD9*, Nikolaos Kanellias1*, Anastasia Pouli, MD, PhD4, Efstathios Kastritis, MD1* and Meletios Dimopoulos, MD1

1Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece
2Hematology Division, Department of Internal Medicine, University of Patras, Medical School, Patras, Greece
3Department of Hematology, Democritus University of Thrace Medical School, Alexandroupolis, Greece
4Hematology Department, "St. Savvas" Oncology Hospital, Athens, Greece
5Department of Hematology, Theagenio Cancer Hospital, Athens, Greece
6Department of Hematology, Faculty of Medicine, University of Ioannina, Ioannina, Greece
7Department of Hematology, Metaxa Cancer Hospital, Piraeus, Greece
8Department of Hematology of University Hospital of Larisa, Faculty of Medicine, University of Thessaly, Larisa, Greece
9Health Data Specialists, Dublin, Ireland

Introduction

Despite the rapidly evolving treatment landscape of multiple myeloma (MM), nearly all patients (pts) eventually relapse. Combining a monoclonal antibody (mAb) with a proteasome inhibitor (PI) or an immunomodulatory drug (IMiD), along with low-dose dexamethasone (Dex) has led to significant clinical improvements in pts with relapsed/refractory MM (RRMM). On that basis, current guidelines recommend such triplet regimens at relapse. Isatuximab (Isa), a novel anti-CD38 mAb, has been approved in combination with pomalidomide (Pom) and low-dose Dex for the treatment of RRMM pts who have received ≥2 prior therapies including lenalidomide and a PI, and have progressed on the last therapy, based on the positive results of the phase 3 ICARIA-MM study. Herein, we report preliminary results from the EAE115 study, which investigates the efficacy and safety of IsaPomDex in an earlier setting, specifically in MM pts experiencing their first relapse after treatment with a lenalidomide-containing regimen.

Methods

EAE115 (NCT05298683) is an investigator-initiated, phase 2, prospective, open-label, multicenter study currently underway in Greece, aiming to enroll 108 adult RRMM pts who have received only one prior line of treatment containing lenalidomide and a PI. 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 who have received previous anti-CD38 mAb therapy, Pom or stem cell transplantation within 12 weeks prior to treatment initiation are excluded. Pts initially receive six 28-day cycles of Isa 10 mg/kg IV (once weekly [QW] in cycle 1, then every two weeks [QW2]) plus Pom 4 mg/day PO (days 1-21) and Dex 40 mg (or 20 mg if ≥75 years) PO/IV (QW). Thereafter, pts achieving at least very good partial response (VGPR) are randomized 1:1 to receive Isa QW2 or QW4 plus PomDex, while pts achieving <VGPR continue treatment with Isa QW2 plus PomDex. The study primary endpoint is the 6-month overall response rate (ORR; defined as partial response [PR] or better) to IsaPomDex.

Results

As of 31 May 2024 (data cut-off), 39 patients had received ≥1 dose of IsaPomDex and thus are included in this analysis. Of these, 24 (61.5%) pts were still under treatment and 15 (38.5%) had discontinued due to progressive disease (8 pts; 20.5%), death (4 pts; 10.3%), consent withdrawal (2 pts; 5.1%) or physician’s decision (1 pt; 2.6%). The median age at baseline was 72.0 years (range 60.0-87.0), with 24 (61.5%) pts being male. Thirty-seven (94.9%) pts had ECOG PS ≤1, 19 (48.7%) pts had stage I and 17 (43.6%) stage II disease as per the revised International Staging System (R-IIS), 8 (20.5%) had high-risk cytogenetics, 19 (48.7%) had lytic bone lesions and 3 (7.7%) had soft-tissue plasmacytomas. Twenty-seven (69.2%) pts had achieved ≥VGPR in the previous line, while 8 (20.5%) had undergone autologous stem cell transplantation (ASCT). At a median follow-up of 7.4 months (range 0.7-19.0), pts have reached a median of 7 cycles of IsaPomDex (range 1-20), with 23 (59.0%) pts having completed ≥6 cycles. Among 34 response-evaluable pts, the ORR was 73.5% with 29.4% achieving ≥VGPR. The median time to first response was 1.0 month (range 0.9-13.8). Thirty-three (84.6%) pts experienced ≥1 treatment-emergent AE (TEAE) and 14 (35.9%) ≥1 serious TEAE. Grade ≥3 TEAEs occurred in 25 (64.1%) pts, with neutropenia being the most common (18 pts; 46.2%).

Conclusion

In this preliminary analysis, IsaPomDex demonstrated promising clinical activity, with rapid responses in pts at first relapse following treatment with a lenalidomide-containing regimen. The safety of IsaPomDex was consistent with the known safety profile of this combination. As study enrollment is still ongoing, further data and longer follow-up are expected to better characterize the safety and efficacy of the combination in this patient population.

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

*signifies non-member of ASH