Ixazomib maintenance therapy in newly diagnosed multiple myeloma: An integrated analysis of four phase I/II studies

Meletios A. Dimopoulos, Jacob P. Laubach, Maria Asunción Echeveste Gutierrez, Norbert Grzasko, Craig C. Hofmeister, Jesus F. San-Miguel, Shaji K Kumar, Richard Labotka, Vickie Lu, Deborah Berg, Catriona Byrne, Zhaoyang Teng, Guohui Liu, Helgi van de Velde, Paul G. Richardson

Research output: Contribution to journalArticle

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Abstract

Objectives: To evaluate the safety and efficacy of maintenance therapy with the oral proteasome inhibitor ixazomib in patients with newly diagnosed multiple myeloma (NDMM) not undergoing transplantation. Methods: Data were pooled from four NDMM phase I/II studies; patients received induction therapy with once- or twice-weekly ixazomib plus lenalidomide-dexamethasone (IRd), melphalan-prednisone (IMP), or cyclophosphamide-dexamethasone (ICd), followed by single-agent ixazomib maintenance, given at the last tolerated dose during induction, until disease progression, death, or unacceptable toxicity. Results: A total of 121 patients achieved stable disease or better after induction (weekly IRd, n = 25; twice-weekly IRd, n = 18; weekly or twice-weekly IMP, n = 35; weekly ICd, n = 43) and received ≥ 1 dose of ixazomib maintenance. Grade ≥ 3 drug-related adverse events occurred in 24% of patients during maintenance; each event was reported in ≤2% of patients. Rates of complete response were 22% after induction and 35% after maintenance. A total of 28 patients (23%) improved their response during maintenance. Conclusions: Ixazomib maintenance following ixazomib-based induction is associated with deepening of responses and a positive safety profile with no cumulative toxicity in patients with NDMM not undergoing transplantation, suggesting that ixazomib is feasible for long-term administration. Phase III investigation of ixazomib maintenance is ongoing.

Original languageEnglish (US)
Pages (from-to)494-503
Number of pages10
JournalEuropean Journal of Haematology
Volume102
Issue number6
DOIs
StatePublished - Jun 1 2019

Fingerprint

Multiple Myeloma
Maintenance
Dexamethasone
Melphalan
Therapeutics
Prednisone
Cyclophosphamide
Transplantation
Safety
Inosine Monophosphate
Proteasome Inhibitors
ixazomib
Drug-Related Side Effects and Adverse Reactions
Disease Progression

Keywords

  • clinical trials
  • multiple myeloma

ASJC Scopus subject areas

  • Hematology

Cite this

Dimopoulos, M. A., Laubach, J. P., Echeveste Gutierrez, M. A., Grzasko, N., Hofmeister, C. C., San-Miguel, J. F., ... Richardson, P. G. (2019). Ixazomib maintenance therapy in newly diagnosed multiple myeloma: An integrated analysis of four phase I/II studies. European Journal of Haematology, 102(6), 494-503. https://doi.org/10.1111/ejh.13231

Ixazomib maintenance therapy in newly diagnosed multiple myeloma : An integrated analysis of four phase I/II studies. / Dimopoulos, Meletios A.; Laubach, Jacob P.; Echeveste Gutierrez, Maria Asunción; Grzasko, Norbert; Hofmeister, Craig C.; San-Miguel, Jesus F.; Kumar, Shaji K; Labotka, Richard; Lu, Vickie; Berg, Deborah; Byrne, Catriona; Teng, Zhaoyang; Liu, Guohui; van de Velde, Helgi; Richardson, Paul G.

In: European Journal of Haematology, Vol. 102, No. 6, 01.06.2019, p. 494-503.

Research output: Contribution to journalArticle

Dimopoulos, MA, Laubach, JP, Echeveste Gutierrez, MA, Grzasko, N, Hofmeister, CC, San-Miguel, JF, Kumar, SK, Labotka, R, Lu, V, Berg, D, Byrne, C, Teng, Z, Liu, G, van de Velde, H & Richardson, PG 2019, 'Ixazomib maintenance therapy in newly diagnosed multiple myeloma: An integrated analysis of four phase I/II studies', European Journal of Haematology, vol. 102, no. 6, pp. 494-503. https://doi.org/10.1111/ejh.13231
Dimopoulos MA, Laubach JP, Echeveste Gutierrez MA, Grzasko N, Hofmeister CC, San-Miguel JF et al. Ixazomib maintenance therapy in newly diagnosed multiple myeloma: An integrated analysis of four phase I/II studies. European Journal of Haematology. 2019 Jun 1;102(6):494-503. https://doi.org/10.1111/ejh.13231
Dimopoulos, Meletios A. ; Laubach, Jacob P. ; Echeveste Gutierrez, Maria Asunción ; Grzasko, Norbert ; Hofmeister, Craig C. ; San-Miguel, Jesus F. ; Kumar, Shaji K ; Labotka, Richard ; Lu, Vickie ; Berg, Deborah ; Byrne, Catriona ; Teng, Zhaoyang ; Liu, Guohui ; van de Velde, Helgi ; Richardson, Paul G. / Ixazomib maintenance therapy in newly diagnosed multiple myeloma : An integrated analysis of four phase I/II studies. In: European Journal of Haematology. 2019 ; Vol. 102, No. 6. pp. 494-503.
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AU - Echeveste Gutierrez, Maria Asunción

AU - Grzasko, Norbert

AU - Hofmeister, Craig C.

AU - San-Miguel, Jesus F.

AU - Kumar, Shaji K

AU - Labotka, Richard

AU - Lu, Vickie

AU - Berg, Deborah

AU - Byrne, Catriona

AU - Teng, Zhaoyang

AU - Liu, Guohui

AU - van de Velde, Helgi

AU - Richardson, Paul G.

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N2 - Objectives: To evaluate the safety and efficacy of maintenance therapy with the oral proteasome inhibitor ixazomib in patients with newly diagnosed multiple myeloma (NDMM) not undergoing transplantation. Methods: Data were pooled from four NDMM phase I/II studies; patients received induction therapy with once- or twice-weekly ixazomib plus lenalidomide-dexamethasone (IRd), melphalan-prednisone (IMP), or cyclophosphamide-dexamethasone (ICd), followed by single-agent ixazomib maintenance, given at the last tolerated dose during induction, until disease progression, death, or unacceptable toxicity. Results: A total of 121 patients achieved stable disease or better after induction (weekly IRd, n = 25; twice-weekly IRd, n = 18; weekly or twice-weekly IMP, n = 35; weekly ICd, n = 43) and received ≥ 1 dose of ixazomib maintenance. Grade ≥ 3 drug-related adverse events occurred in 24% of patients during maintenance; each event was reported in ≤2% of patients. Rates of complete response were 22% after induction and 35% after maintenance. A total of 28 patients (23%) improved their response during maintenance. Conclusions: Ixazomib maintenance following ixazomib-based induction is associated with deepening of responses and a positive safety profile with no cumulative toxicity in patients with NDMM not undergoing transplantation, suggesting that ixazomib is feasible for long-term administration. Phase III investigation of ixazomib maintenance is ongoing.

AB - Objectives: To evaluate the safety and efficacy of maintenance therapy with the oral proteasome inhibitor ixazomib in patients with newly diagnosed multiple myeloma (NDMM) not undergoing transplantation. Methods: Data were pooled from four NDMM phase I/II studies; patients received induction therapy with once- or twice-weekly ixazomib plus lenalidomide-dexamethasone (IRd), melphalan-prednisone (IMP), or cyclophosphamide-dexamethasone (ICd), followed by single-agent ixazomib maintenance, given at the last tolerated dose during induction, until disease progression, death, or unacceptable toxicity. Results: A total of 121 patients achieved stable disease or better after induction (weekly IRd, n = 25; twice-weekly IRd, n = 18; weekly or twice-weekly IMP, n = 35; weekly ICd, n = 43) and received ≥ 1 dose of ixazomib maintenance. Grade ≥ 3 drug-related adverse events occurred in 24% of patients during maintenance; each event was reported in ≤2% of patients. Rates of complete response were 22% after induction and 35% after maintenance. A total of 28 patients (23%) improved their response during maintenance. Conclusions: Ixazomib maintenance following ixazomib-based induction is associated with deepening of responses and a positive safety profile with no cumulative toxicity in patients with NDMM not undergoing transplantation, suggesting that ixazomib is feasible for long-term administration. Phase III investigation of ixazomib maintenance is ongoing.

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