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Combination Therapy for Frail and Unfit Patients Newly Diagnosed With Multiple Myeloma

By: Joseph Fanelli
Posted: Thursday, January 30, 2020

For unfit and frail patients with newly diagnosed multiple myeloma who are ineligible for transplantation, treatment with ixazomib and daratumumab plus low-dose dexamethasone may prove to be an effective regimen, according to findings from the phase II HOVON 143 trial, presented at the 2019 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract 695) and published in the journal Blood. However, Claudia A.M. Stege, MD, of the Vrije Universiteit Amsterdam, Netherlands, and colleagues observed early mortality due to vulnerability and infections in this patient population, indicating that “better identification and support of those patients is warranted.”

In this prospective trial, the investigators administered 28-day induction cycles of ixazomib and daratumumab plus dexamethasone, followed by maintenance therapy with ixazomib and daratumumab until disease progression, to patients with newly diagnosed multiple myeloma. The patients enrolled were classified as unfit (65 patients) and frail (67 patients) based on the International Myeloma Working Group frailty index. Overall response rate, progression-free survival, overall survival, treatment discontinuation, and toxicity were reported for the first 23 eligible patients from both groups of patients (mortality rates were reported for all enrolled).

For unfit patients, the overall response rate was 87% during induction, compared with 78% for frail patients. For unfit patients, the 9-month progression-free survival rate was 78%, whereas for frail patients, it was 61%. The 9-month overall survival rates for unfit and frail patients were 100% and 83%, respectively. In addition, the mortality rate for unfit patients was 2%, compared with 13% for frail patients.

Of the unfit patients, 16 completed induction treatment (70%), compared with 14 frail patients (61%). The authors reported that hematologic toxicity was limited mainly to neutropenia and thrombocytopenia (the latter occurring in frail patients alone). Nonhematologic toxicity, conversely, was found to be manageable for patients, with grade 3 infections occurring in 9% of both patient groups.

Disclosure: For full disclosures of the study authors, visit

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