Session: 653. Myeloma and Plasma Cell Dyscrasias: Prospective Therapeutic Trials: Poster II
Hematology Disease Topics & Pathways:
clinical trials, Research, Combination therapy, Clinical Research, Therapies
Study Design and Methods: This is a phase II trial to evaluate the efficacy of Isa-KRD in 50 transplant-eligible NDMM (NCT04430894). All patients received 4 cycles of induction therapy with Isa-KRd followed by stem cell collection with the option to proceed to upfront versus deferred stem cell transplant (SCT) at investigator’s discretion. Patients undergoing upfront SCT received 2 additional cycles of therapy then maintenance. Patients deferring SCT following collection received 4 additional cycles of therapy then maintenance. Each 28-day cycle consisted of isa 10 mg/kg iv weekly cycles 1-2, Q2 weeks cycles 3-6, Q4 weeks thereafter; carfilzomib (20 mg/m2 cycle 1, day 1 only) 56 mg/m2 iv days 1, 8, 15; lenalidomide 25 mg po days 1-21; and dexamethasone 20 mg po days 1, 2, 8, 9, 15, and 16 (and days 22, 23 cycles 1-2).
For maintenance, patients were stratified based on cytogenetics (high-risk cytogenetics included deletion 17p, gain of 1q, and translocations t(4:14), t(14;16), t(14;20)). Patients with standard-risk cytogenetics received lenalidomide 10 mg po days 1-21. Patients with high-risk cytogenetics received isatuximab 10 mg/kg iv day 1; carfilzomib 56 mg/m2 iv days 1, 15; lenalidomide 10 mg po days 1-21.
Main Outcomes and Measures: The primary end point is complete response (CR + stringent CR) rate after 4 cycles of Isa-KRd as assessed by the International Myeloma Working Group response criteria. Secondary endpoints included determining safety and tolerability of Isa-KRd; minimal residual disease (MRD) after 4 cycles, at completion of consolidation (post-transplant) or induction (transplant-deferred) and at 24 months; progression-free survival (PFS), overall survival (OS) rates, and quality of life.
Results: Fifty patients enrolled between August 2020 and February 2022. Median age at study entry was 59 years (range 39-70) and 27 (54%) were male. Twenty-three (46%) of patients had high-risk cytogenetics, 6 (12%) were ISS III, and 2 (4%) were R-ISS III. Median follow up was 10.8 months. Of the 47 patients evaluable for response after 4 cycles, the ORR was 100% and 89% (42/47) achieved a very good partial response (VGPR) or better and 40% (19/47) a CR. Of the 47 patients evaluable for response, MRD results were available after C4 for 28 patients achieving a VGPR or better. Of those, 43% (12/28) were MRD negative at 10-5 and 32% (9/28) at 10-6. The 12-month PFS and OS were 97.9% (95% CI 86.1% -99.7%). Most common grade 3 or 4 side effects (≥2 patients) were neutropenia (24%), elevated alanine aminotransferase (10%), acute kidney injury (6%), and thrombocytopenia (6%). Grade 1-2 infusion-related reactions were seen in 20%, no grade 3. Grade 1-2 hypertension was seen in 48% with one grade 3. There was one death assessed as unrelated. Two patients were removed from study for acute kidney injury.
Conclusions: Early data suggest that Isa-KRd induces deep responses in patients with NDMM. The overall safety profile is expected and consistent with previous reports of similar regimen.
Disclosures: O'Donnell: Janssen: Consultancy; BMS: Consultancy, Honoraria. Nadeem: Takeda: Research Funding; GSK: Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; GPCR Therapeutics: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding. Yee: Bristol Myers Squibb: Consultancy, Research Funding; Sanofi: Consultancy; Regeneron: Consultancy; Oncopeptides: Consultancy; Karyopharm: Consultancy; Janssen: Consultancy, Research Funding; Celgene: Consultancy; Takeda: Consultancy; Amgen: Consultancy, Research Funding; GlaxoSmithKline: Consultancy; AbbVie: Consultancy; Adaptive Biotechnologies: Consultancy. Branagan: Karyopharm Therapeutics: Consultancy; Janssen/Pharmacyclics: Consultancy; Adaptive Biotechnologies: Consultancy; BeiGene: Consultancy; CSL Behring: Consultancy; Genzyme: Consultancy. Rosenblatt: Wolters Kluwer Health Inc: Other: Spouse COI; Karyopharm Therapeutics: Other: DSMB; Dava Oncology: Other: Education; Celgene: Membership on an entity's Board of Directors or advisory committees; Partner Tx: Membership on an entity's Board of Directors or advisory committees; Attivare Therapeutics: Consultancy; Bioclinica: Consultancy; Imaging Endpoint: Consultancy; Parexel: Consultancy; Kite: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Merck: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Sanofi: Research Funding; BMS: Research Funding; Celgene: Research Funding; Kite: Honoraria. Richardson: Abbvie: Consultancy; Protocol Intelligence: Consultancy; Secura Bio: Consultancy; GlaxoSmithKline: Consultancy; Regeneron: Consultancy; AstraZeneca: Consultancy; Oncopeptides: Consultancy, Research Funding; Sanofi: Consultancy; Takeda: Consultancy, Research Funding; Karyopharm: Consultancy, Research Funding; Celgene/BMS: Consultancy, Research Funding. Raje: Medscape: Honoraria; Amgen: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria; Celgene: Honoraria; Research to Practice: Honoraria; Two Seventy Bio: Research Funding; Massachusetts General Hospita: Current Employment; Janssen: Consultancy, Honoraria.
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