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. 2025 Mar 1;110(3):758-763.
doi: 10.3324/haematol.2024.285916.

Ixazomib, pomalidomide and dexamethasone in relapsed or refractory multiple myeloma characterized with highrisk cytogenetics: the IFM 2014-01 study

Arthur Bobin  1 , Salomon Manier  2 , Joe De Keizer  3 , Jaydeep K Srimani  4 , Cyrille Hulin  5 , Lionel Karlin  6 , Denis Caillot  7 , Ingrid Lafon  7 , Clara Mariette  8 , Carla Araujo  9 , Bertrand Arnulf  10 , Benoît Bareau  11 , Karim Belhadj  12 , Lofti Benboubker  13 , Thorsten Braun  14 , Claire Calmettes  15 , Olivier Decaux  16 , Mamoun Dib  17 , Hélène Demarquette  18 , Caroline Jacquet  19 , Cécile Sonntag  20 , Sophie Godet  21 , Arnaud Jaccard  22 , Pascal Lenain  23 , Margaret Macro  24 , Valentine Richez-Olivier  25 , Mourad Tiab  26 , Laure Vincent  27 , Hacene Zerazhi  28 , Marie-Odile Pétillon  29 , Sandrine Rollet  29 , Helene Gardeney  1 , Geraldine Durand  1 , Anthony Levy  30 , Cyrille Touzeau  31 , Aurore Perrot  32 , Philippe Moreau  31 , Thierry Facon  2 , Jill Corre  33 , Stephanie Ragot  3 , Herve Avet-Loiseau  33 , Xavier Leleu  34
Affiliations

Ixazomib, pomalidomide and dexamethasone in relapsed or refractory multiple myeloma characterized with highrisk cytogenetics: the IFM 2014-01 study

Arthur Bobin et al. Haematologica. .
No abstract available

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Figures

Figure 1.
Figure 1.
Survival from study entry (N=26) - time to progression. (A) Overall population. (B) According to high-risk relapsed/refractory multiple myeloma (HR RRMM) population, either del(17p), or t(4;14) or del(17p) and t(4;14). (C) Overall, population as a whole. (D) According to HR RRMM population, either del(17p), or t(4;14) or del(17p) and t(4;14). The median time to progression (TTP) and overall survival (OS) were at 10.5 (95% confidence interval [CI]: 7.9-not estimable [NE]) and NE (95% CI: 27.1-NE), as a whole, respectively. Kaplan-Meier method was used to analyze time-to-event data. Results were expressed as median time-to-event in months and 95% CI. Pharmacokinetic (PK) analysis (N=26). (E) The patients are stratified by best response over the course of the study. Sparse pharmacokinetic (PK) samples were collected from patients on days 1 and 11 of cycle 1, then pre-dose for cycles 2 to 5. The objective was to study whether PK analysis would differ in HR RRMM from previous studies using the same dose schedule of ixazomib (MLN2238). The systemic ixazomib concentrations were quantified from patient plasma samples using a validated liquid chromatography/tandem mass spectrometry assay with a range of 0.5 to 500 ng/mL. Given that ixazomib exhibits dose-proportional PK, all PK concentrations in this analysis were normalized by the corresponding dose administered; these normalized values enable the comparison across studies and dose levels. The dose-normalized PK concentrations in our study were comparable with a previous single-agent dose escalation trial which utilized the same dose regimen (clinicaltrials gov Identifier: NCT00932698) and the dose-normalized PK concentrations were comparable across patient response subgroups. These results are consistent with previous model-driven exposure-response analyses that concluded ixazomib exposures were not a statistically significant predictor of complete response (CR), ≥ very good partial response (≥VGPR), or ≥ partial response (≥PR) rate. Despite a slight trend toward higher values observed in patients who experienced a PR/VG-PR response, this data supports that HR RRMM patients don’t seem to have different PK concentrations’ of ixazomib, independently of the dose density or intensity of the drug. This data does not support, therefore, the use of the serum concentration of ixazomib as a potential biomarker to tailor treatment schema of ixazomib and better determine dose density over intensity in order to optimize the activity of Ixazomib in RRMM HR. MR: minor response; NA: not applicable; PD: progressive disease; SD: stable disease; Conc: concentration.
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References

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