Randomized phase 2 trial of ixazomib and dexamethasone in relapsed multiple myeloma not refractory to bortezomib

Shaji K Kumar, Betsy R. LaPlant, Craig B. Reeder, Vivek Roy, Alese E. Halvorson, Francis Buadi, Morie Gertz, Peter Leif Bergsagel, Angela Dispenzieri, Melanie A. Thompson, Jamie Crawley, Prashant Kapoor, Joseph R Mikhael, Alexander Keith Stewart, Suzanne R. Hayman, Yi L. Hwa, Wilson Gonsalves, Thomas Elmer Witzig, Sikander Ailawadhi, David M Dingli & 5 others Ronald S. Go, Yi Lin, Candido E Rivera, S Vincent Rajkumar, Martha Lacy

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Proteasome inhibitors have become an integral part of myeloma therapy. Considerable efforts have gone into optimizing this therapeutic approach to obtain maximal proteasome inhibition with least toxicity. Ixazomib is the first oral proteasome inhibitor to enter the clinic and has been studied as a single agent as well as in various combinations. The current trial was designed to examine the efficacy and toxicity of combining 2 different doses of ixazomib (4 mg and 5.5 mg given weekly for 3 of 4 weeks) with 40 mg weekly of dexamethasone, in relapsed myeloma. Seventy patients were enrolled, 35 patients randomly assigned to each ixazomib dose. Overall, 30 (43%; 95% confidence interval, 31-55) of the patients achieved a confirmed partial response or better, with 31% achieving a response with 4 mg and 54% with 5.5 mg of ixazomib. The median event-free survival (EFS) for the entire study population was 8.4 months; 1-year overall survival was 96%. The EFS was 5.7 months for patients with prior bortezomib exposure and 11.0months for bortezomib-naíve patients.Agrade 3 or 4 adverse event considered at least possibly related to treatment was seen in 11 (32%) patients at 4mgand in 21 (60%) at 5.5 mg. Dose reductions were more frequent with 5.5 mg dose. Overall, the ixazomib with dexamethasone has good efficacy in relapsed myeloma, is well-tolerated and with higher response rate at 5.5 mg, albeit with more toxicity.

Original languageEnglish (US)
Pages (from-to)2415-2422
Number of pages8
JournalBlood
Volume128
Issue number20
DOIs
StatePublished - Nov 17 2016

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Multiple Myeloma
Refractory materials
Dexamethasone
Toxicity
Proteasome Inhibitors
Disease-Free Survival
Proteasome Endopeptidase Complex
Bortezomib
ixazomib
Therapeutics
Confidence Intervals
Survival
Population

ASJC Scopus subject areas

  • Immunology
  • Biochemistry
  • Hematology
  • Cell Biology

Cite this

Randomized phase 2 trial of ixazomib and dexamethasone in relapsed multiple myeloma not refractory to bortezomib. / Kumar, Shaji K; LaPlant, Betsy R.; Reeder, Craig B.; Roy, Vivek; Halvorson, Alese E.; Buadi, Francis; Gertz, Morie; Bergsagel, Peter Leif; Dispenzieri, Angela; Thompson, Melanie A.; Crawley, Jamie; Kapoor, Prashant; Mikhael, Joseph R; Stewart, Alexander Keith; Hayman, Suzanne R.; Hwa, Yi L.; Gonsalves, Wilson; Witzig, Thomas Elmer; Ailawadhi, Sikander; Dingli, David M; Go, Ronald S.; Lin, Yi; Rivera, Candido E; Rajkumar, S Vincent; Lacy, Martha.

In: Blood, Vol. 128, No. 20, 17.11.2016, p. 2415-2422.

Research output: Contribution to journalArticle

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T1 - Randomized phase 2 trial of ixazomib and dexamethasone in relapsed multiple myeloma not refractory to bortezomib

AU - Kumar, Shaji K

AU - LaPlant, Betsy R.

AU - Reeder, Craig B.

AU - Roy, Vivek

AU - Halvorson, Alese E.

AU - Buadi, Francis

AU - Gertz, Morie

AU - Bergsagel, Peter Leif

AU - Dispenzieri, Angela

AU - Thompson, Melanie A.

AU - Crawley, Jamie

AU - Kapoor, Prashant

AU - Mikhael, Joseph R

AU - Stewart, Alexander Keith

AU - Hayman, Suzanne R.

AU - Hwa, Yi L.

AU - Gonsalves, Wilson

AU - Witzig, Thomas Elmer

AU - Ailawadhi, Sikander

AU - Dingli, David M

AU - Go, Ronald S.

AU - Lin, Yi

AU - Rivera, Candido E

AU - Rajkumar, S Vincent

AU - Lacy, Martha

PY - 2016/11/17

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N2 - Proteasome inhibitors have become an integral part of myeloma therapy. Considerable efforts have gone into optimizing this therapeutic approach to obtain maximal proteasome inhibition with least toxicity. Ixazomib is the first oral proteasome inhibitor to enter the clinic and has been studied as a single agent as well as in various combinations. The current trial was designed to examine the efficacy and toxicity of combining 2 different doses of ixazomib (4 mg and 5.5 mg given weekly for 3 of 4 weeks) with 40 mg weekly of dexamethasone, in relapsed myeloma. Seventy patients were enrolled, 35 patients randomly assigned to each ixazomib dose. Overall, 30 (43%; 95% confidence interval, 31-55) of the patients achieved a confirmed partial response or better, with 31% achieving a response with 4 mg and 54% with 5.5 mg of ixazomib. The median event-free survival (EFS) for the entire study population was 8.4 months; 1-year overall survival was 96%. The EFS was 5.7 months for patients with prior bortezomib exposure and 11.0months for bortezomib-naíve patients.Agrade 3 or 4 adverse event considered at least possibly related to treatment was seen in 11 (32%) patients at 4mgand in 21 (60%) at 5.5 mg. Dose reductions were more frequent with 5.5 mg dose. Overall, the ixazomib with dexamethasone has good efficacy in relapsed myeloma, is well-tolerated and with higher response rate at 5.5 mg, albeit with more toxicity.

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