Session: 654. Multiple Myeloma: Pharmacologic Therapies: Poster I
Hematology Disease Topics & Pathways:
Research, Clinical trials, Clinical Research
Objectives: The aim of this study was to assess the safety and efficacy of Isa-Kd utilizing standard Isa-dosing (10 mg/kg QWk x4, then QOWk) and weekly high-dose K (70 mg/m2) plus dexamethasone (d) in patients with early relapsed MM (1-3 prior LOT). (NCT-02332850)
Methods: Eligible patients (pts) had disease progression after 1-3 prior LOT, an ECOG <3, no prior CD38 therapy, and adequate organ function. Therapy included Isa IV weekly (QW) for 4 doses then Q2W together with K (20mg/m2 Day 1, =>70 mg/m2: Day 8, 15 Q28d and for all subsequent K doses) and d (40 mg PO QW). Pts continued therapy until disease progression, undue toxicity or physician/patient choice.
Results: As of July 14, 2024, 50 pts have been enrolled and are evaluable for safety and response. Pts were ECOG <2, had a median age of 64 (range 39-78) yrs, received a median of 1 LOT (range 1-3) and 90% had received prior SCT. All pts were IMiD and PI exposed, 50% Len refractory (Refr), and 22% had received prior K. Median follow-up is 14 months (range 2-43m), and a median of 16 cycles of Isa-Kd have been administered. The ORR is 90% (sCR/CR 8, VGPR 21, PR 16), responses occur rapidly (median 1 cycle) and responses deepen over time. The median progression free and overall survival have not been reached. Disposition: 14 patients have progressed; 3 patients have died (1 from PD, 1 sudden death attributed to K, 1 sudden death off treatment), 17 pts stopped treatment in response (7 due to toxicity (3 SOB, 1 MI, 1 FTT, 1 colitis, 1 fatigue); 6 for treatment holiday; 4 due to physician choice, and 16 remain on therapy).
The most frequent occurring treatment-related toxicity (AEs-all grades, incidence ≥ 20%), were infusion related reactions (IRR; 58%), hypertension (52%), nausea (50%), cough (42%), fatigue (40%), dyspepsia (40%), insomnia (38%), diarrhea (38%), thrombocytopenia (34%), fever (26%), headache (24%), constipation (22%), and anemia (20%). Infections were also common; 30 pts (60%) experienced an URI, 10 pts (20%) had covid, and an additional 17 pts experienced a presumed bacterial infection (5 sinusitis, 4 UTI, 3 pneumonia, 3 cellulitis, 2 colitis). The IRRs were all attributable to Isa, all were Grade 1-2 and only 2 pts had a subsequent or second IRR.
Conclusion: The triplet combination of Isa-Kd incorporating weekly high-dose K70 mg/m2 appears safe; with no unexpected toxicity and AEs consistent with the toxicity profile of the individual agents. Encouraging anti-MM activity has been demonstrated with an ORR of 90% in patients with early RRMM (1-3 PLOT) and the median PFS and OS have not been reached (NCT 02332850).
Disclosures: Vesole: BMS: Speakers Bureau; Karyopharm: Speakers Bureau; Amgen: Speakers Bureau; Takeda: Speakers Bureau; Janssen: Speakers Bureau; Sanofi: Speakers Bureau. Martin: Poseida: Research Funding; Janssen: Research Funding; BMS: Research Funding; Sanofi: Research Funding; GSK, Pfizer, Roche: Honoraria. Trudel: Sanofi, GSK, Pfizer, BMS, Janssen, AstraZeneca, BMS, Forus: Honoraria; GSK, BMS, Roche, Genentech, Pfizer, Janssen, K36 Therapeutics: Research Funding; GSK, BMS, Roche: Consultancy, Honoraria, Research Funding; Princess Margaret Cancer Centre: Current Employment. Shenoy: Janssen: Honoraria. Biran: Pfizer: Consultancy, Honoraria; Sanofi: Honoraria, Speakers Bureau; AbbVie: Consultancy; Karyopharm: Research Funding; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen: Research Funding. Wolf: Adaptive: Consultancy. Matous: BeiGene; Pharmacyclics: Consultancy. Berdeja: Janssen: Honoraria; 2 Seventy Bio; Abbvie; Amgen; BMS; C4 Therapeutics; Caribou Biosciences; CARsgen; Cartesian Therapeutics; Celularity; CRISPR Therapeutics; Fate Therapeutics; Genentech; GSK; Ichnos Sciences; Incyte; Janssen; Juno Therapeutics; K36 Therapeutics; Karyopharm: Research Funding; AstraZeneca; BMS; Caribou Biosciences; Galapagos; Janssen; K36 Therapeutics; Kite Pharma; Legend Biotech; Pfizer; Roche; Sanofi-Aventis; and Takeda: Consultancy.
OffLabel Disclosure: Isatuximab: CD38 antibody - being tested with high-dose weekly Carfilzomib
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