TY - JOUR
T1 - Ixazomib, Daratumumab, and Low-Dose Dexamethasone in Frail Patients With Newly Diagnosed Multiple Myeloma
T2 - The Hovon 143 Study
AU - Stege, Claudia A.M.
AU - Nasserinejad, Kazem
AU - van der Spek, Ellen
AU - Bilgin, Yavuz M.
AU - Kentos, Alain
AU - Sohne, Maaike
AU - van Kampen, Roel J.W.
AU - Ludwig, Inge
AU - Thielen, Noortje
AU - Durdu-Rayman, Nazik
AU - de Graauw, Nicole C.H.P.
AU - van de Donk, Niels W.C.J.
AU - de Waal, Esther G.M.
AU - Vekemans, Marie Christiane
AU - Timmers, Gert Jan
AU - van der Klift, Marjolein
AU - Soechit, Savita
AU - Geerts, Paul A.F.
AU - Silbermann, Matthijs H.
AU - Oosterveld, Margriet
AU - Nijhof, Inger S.
AU - Sonneveld, Pieter
AU - Klein, Saskia K.
AU - Levin, Mark David
AU - Zweegman, Sonja
PY - 2021/9/1
Y1 - 2021/9/1
N2 - PURPOSE: Frail patients with newly diagnosed multiple myeloma have an inferior outcome, mainly because of a high discontinuation rate due to toxicity. We designed a phase II trial specifically for frail patients, evaluating the efficacy and tolerability of ixazomib-daratumumab-low-dose-dexamethasone (Ixa-Dara-dex). METHODS: Sixty-five patients, who were frail according to the International Myeloma Working Group frailty index, were treated with nine induction cycles Ixa-Dara-dex followed by maintenance with Ixa-Dara for a maximum of 2 years. RESULTS: The overall response rate on induction therapy was 78%. After a median follow-up of 22.9 months, median progression-free survival (PFS) was 13.8 months and 12-month overall survival (OS) was 78%. Median PFS and 12-month OS were 21.6 months and 92% in patients who were frail based on age > 80 years alone, versus 13.8 months and 78%, and 10.1 months and 70% in patients who were frail based on additional frailty parameters either ≤ 80 or > 80 years of age, respectively. In 51% of patients, induction therapy had to be discontinued prematurely, of which 6% because of noncompliance to study treatment, 9% because of toxicity, and 9% because of death (8% within 2 months, of which 80% because of toxicity). Quality of life improved during induction treatment, being clinically meaningful already after three induction cycles. CONCLUSION: Ixa-Dara-dex lead to a high response rate and improved quality of life. However, treatment discontinuation because of toxicity and early mortality, negatively influencing PFS and OS, remains a concern in frail patients. The outcome was heterogeneous across frail subpopulations. This should be taken into account in the design and interpretation of future studies in frail patients, to pave the way for more precise treatment guidance.
AB - PURPOSE: Frail patients with newly diagnosed multiple myeloma have an inferior outcome, mainly because of a high discontinuation rate due to toxicity. We designed a phase II trial specifically for frail patients, evaluating the efficacy and tolerability of ixazomib-daratumumab-low-dose-dexamethasone (Ixa-Dara-dex). METHODS: Sixty-five patients, who were frail according to the International Myeloma Working Group frailty index, were treated with nine induction cycles Ixa-Dara-dex followed by maintenance with Ixa-Dara for a maximum of 2 years. RESULTS: The overall response rate on induction therapy was 78%. After a median follow-up of 22.9 months, median progression-free survival (PFS) was 13.8 months and 12-month overall survival (OS) was 78%. Median PFS and 12-month OS were 21.6 months and 92% in patients who were frail based on age > 80 years alone, versus 13.8 months and 78%, and 10.1 months and 70% in patients who were frail based on additional frailty parameters either ≤ 80 or > 80 years of age, respectively. In 51% of patients, induction therapy had to be discontinued prematurely, of which 6% because of noncompliance to study treatment, 9% because of toxicity, and 9% because of death (8% within 2 months, of which 80% because of toxicity). Quality of life improved during induction treatment, being clinically meaningful already after three induction cycles. CONCLUSION: Ixa-Dara-dex lead to a high response rate and improved quality of life. However, treatment discontinuation because of toxicity and early mortality, negatively influencing PFS and OS, remains a concern in frail patients. The outcome was heterogeneous across frail subpopulations. This should be taken into account in the design and interpretation of future studies in frail patients, to pave the way for more precise treatment guidance.
UR - http://www.scopus.com/inward/record.url?scp=85115440671&partnerID=8YFLogxK
U2 - https://doi.org/10.1200/JCO.20.03143
DO - https://doi.org/10.1200/JCO.20.03143
M3 - Article
C2 - 33945289
SN - 0732-183X
VL - 39
SP - 2758
EP - 2767
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 25
ER -