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A phase I/ II study of the combination of panobinostat and carfilzomib in patients with relapsed or relapsed/refractory multiple myeloma: Final analysis of second dose‐expansion cohort
Author(s) -
Berdeja Jesus G.,
Gregory Tara K.,
Faber Edward A.,
Hart Lowell L.,
Mace Joseph R.,
Arrowsmith Edward R.,
Flinn Ian W.,
Matous Jeffrey V.
Publication year - 2021
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.26088
Subject(s) - carfilzomib , panobinostat , medicine , refractory (planetary science) , cohort , adverse effect , multiple myeloma , clinical endpoint , neutropenia , gastroenterology , oncology , lenalidomide , surgery , toxicity , clinical trial , gene , histone , biochemistry , chemistry , physics , histone deacetylase , astrobiology
The maximum tolerated dose of the panobinostat and carfilzomib combination in patients with relapsed/refractory multiple myeloma (RRMM) was not reached in our previous dose‐escalation study. We report additional dose levels in the phase I/II, single‐arm, multicenter, standard 3 + 3 dose‐escalation expansion‐cohort study (NCT01496118). Patients with RRMM were treated with panobinostat 30 mg, carfilzomib 20/56 mg/m 2 (N = 3), or panobinostat 20 mg, carfilzomib 20/56 mg/m 2 (N = 33). Treatment cycles lasted 28 days; panobinostat: days 1, 3, 5, 15, 17, 19; carfilzomib: days 1, 2, 8, 9, 15, 16. For dose level 6 (DL 6), median age was 63 years (range, 49–91 years), 60.6% were male, 42.4% were high risk. Patients received a median of two prior therapies (range 1–7); proteasome inhibitors (PI; 100%), immunomodulatory imide drugs (IMiD; 78.8%), and stem cell transplant (36.4%); 48.5%, 51.1%, and 24.2% were refractory to prior PI or prior IMiD treatment or both, respectively. Patients completed a median of seven (range 1–40) treatment cycles. Overall response rate (primary endpoint) of evaluable patients in the expansion cohort (N = 32): 84.4%; clinical benefit rate: 90.6%. With a median follow‐up of 26.1 months (range, 0–72.5 months), median (95% CI) progression‐free survival, time‐to‐progression and overall survival of patients was 10.3 (6.1, 13.9), 11.7 (5.6, 14.5), and 44.6 (20.8, N/A) months, respectively. Common adverse events (AEs) included thrombocytopenia (78.8%), nausea (63.6%), fatigue (63.6%), diarrhea (51.5%), and vomiting (51.5%). Seven patients had serious treatment‐related AEs. There was one treatment‐related death. In conclusion, panobinostat plus carfilzomib is an effective steroid‐sparing regimen for RRMM.