Evidence map›Paper›PMID 29938772›Full record

Trial reportBritish journal of haematology2018

Twice-weekly ixazomib in combination with lenalidomide-dexamethasone in patients with newly diagnosed multiple myeloma.

Paul G Richardson, Craig C Hofmeister, Cara A Rosenbaum, Myo Htut, David H Vesole, Jesus G Berdeja, Michaela Liedtke, Ajai Chari, Stephen D Smith, Daniel Lebovic and 8 more

Registry-linked trialAbstract readClinical Trial, Phase IClinical Trial, Phase IIMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in British journal of haematology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01383928 (An Open-Label, Dose-Escalation, Phase 1/2 Study of the Oral Formulation of IXAZOMIB), which is not on this map. Cited by 14 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 2 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01383928 phase1 / phase2completednot on this map

An Open-Label, Dose-Escalation, Phase 1/2 Study of the Oral Formulation of IXAZOMIB (MLN9708), Administered Twice-weekly in Combination With Lenalidomide and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma Requiring Systemic Treatment

TypeinterventionalSponsorMillennium Pharmaceuticals, Inc.Ran2011 to 2017Enrolled64ConditionsMultiple MyelomaArmsIxazomib, Lenalidomide, Dexamethasone
3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 2 syntheses or guidelines pooled it.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors.

Paul G RichardsonDana-Farber Cancer Institute, Boston, MA, USA.ORCID 0000-0002-7426-8865
Craig C HofmeisterOhio State University, Columbus, OH, USA.
Cara A RosenbaumHematology/Oncology, University of Chicago Medicine, Chicago, IL, USA.
Myo HtutHematology and Stem Cell Transplant, City of Hope National Medical Center Duarte, Duarte, CA, USA.
David H VesoleJohn Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ, USA.
Jesus G BerdejaSarah Cannon Research Institute, Nashville, TN, USA.
Michaela LiedtkeStanford Comprehensive Cancer Center, Stanford, CA, USA.ORCID 0000-0001-8945-5850
Ajai ChariMount Sinai School of Medicine Ruttenberg Treatment Center, New York, NY, USA.
Stephen D SmithFred Hutchinson Cancer Research Center, University of Washington, Seattle, WA, USA.
Daniel LebovicUniversity of Michigan Cancer Center, Ann Arbor, MI, USA.
Noopur RajeMassachusetts General Hospital, Boston, MA, USA.
Catriona ByrneMillennium Pharmaceuticals Inc., Cambridge, MA, USA.
Eileen LiaoMillennium Pharmaceuticals Inc., Cambridge, MA, USA.
Neeraj GuptaMillennium Pharmaceuticals Inc., Cambridge, MA, USA.ORCID 0000-0002-5500-5218
Alessandra Di BaccoMillennium Pharmaceuticals Inc., Cambridge, MA, USA.
Jose EstevamMillennium Pharmaceuticals Inc., Cambridge, MA, USA.
Deborah BergMillennium Pharmaceuticals Inc., Cambridge, MA, USA.
Rachid BazMalignant Hematology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Weekly ixazomib with lenalidomide-dexamethasone (Rd) is feasible and has shown activity in newly diagnosed multiple myeloma (NDMM) patients. This phase 1/2 study (NCT01383928) evaluated the recommended phase 2 dose (RP2D), pharmacokinetics, safety and efficacy of twice-weekly ixazomib plus Rd in NDMM; 64 patients were enrolled across both phases. Patients received twice-weekly oral ixazomib 3·0 or 3·7 mg plus lenalidomide 25 mg and dexamethasone 20 mg (10 mg in cycles 9-16) for up to sixteen 21-day cycles, followed by maintenance with twice-weekly ixazomib alone. No dose-limiting toxicities were reported in cycle 1; the RP2D was 3·0 mg based on overall tolerability across multiple cycles. In 62 evaluable patients, the confirmed overall response rate was 94% (68% ≥very good partial response; 24% complete response). Median progression-free survival was 24·9 months. Responses (median duration 36·9 months for patients receiving the RP2D) deepened during treatment. Grade 3 drug-related adverse events (AEs) occurred in 64% of patients, including: rash, 13%; peripheral neuropathy, 8%; hyperglycaemia, 8%. There were no grade 4 drug-related AEs. Thirteen patients discontinued due to AEs. Twice-weekly ixazomib-Rd offers substantial activity with promising long-term outcomes in NDMM patients but may be associated with greater toxicity compared with weekly ixazomib-Rd in this setting.

Indexed as

Administration, OralAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBoron CompoundsDexamethasoneDisease-Free SurvivalDose-Response Relationship, DrugDrug Administration ScheduleFemaleGlycineHumansLenalidomideMaleMiddle AgedBoron CompoundsDexamethasoneGlycineixazomibLenalidomideixazomibmultiple myelomanewly diagnosedoraltwice-weekly

Identifiers

PMID29938772
PMCPMC6055619

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.