Phase 1 open-label study of panobinostat, lenalidomide, bortezomib + dexamethasone in relapsed and relapsed/refractory multiple myeloma

Additional therapeutic options are needed for relapsed and refractory multiple myeloma (RRMM). We present data from a phase 1b, open-label, dose-escalation study (NCT01965353) of 20 patients with RRMM (median age: 63 years [range: 50–77]) and a median of four prior regimens (range: 2–14); 85% had re...

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Published in:Blood cancer journal (New York) 2021-02, Vol.11 (2), p.20-20, Article 20
Main Authors: Laubach, Jacob P., Tuchman, Sascha A., Rosenblatt, Jacalyn M., Mitsiades, Constantine S., Colson, Kathleen, Masone, Kelly, Warren, Diane, Redd, Robert A., Grayson, Dena, Richardson, Paul G.
Format: Article
Language:English
Subjects:
692/699/1541/1990/804
692/700/565/1436/1437
Biomedical and Life Sciences
Biomedicine
Blood
Cancer Research
Cancer therapies
Hematology
Immunotherapy
Medical prognosis
Multiple myeloma
Neutrophils
Oncology
Patients
Peripheral neuropathy
Response rates
Steroids
Targeted cancer therapy
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Summary:Additional therapeutic options are needed for relapsed and refractory multiple myeloma (RRMM). We present data from a phase 1b, open-label, dose-escalation study (NCT01965353) of 20 patients with RRMM (median age: 63 years [range: 50–77]) and a median of four prior regimens (range: 2–14); 85% had refractory disease (lenalidomide [80%]; bortezomib [75%]; lenalidomide and bortezomib [50%]). Patients received a median of six cycles (range: 1–74) of panobinostat (10 or 15 mg), lenalidomide 15 mg, bortezomib 1 mg/m 2 , and dexamethasone 20 mg (pano-RVd). Median follow-up was ~14 months. Six dose-limiting toxicities were reported (mostly hematological); maximum tolerated dose of panobinostat (primary endpoint) was 10 mg. Most common adverse events (AEs) were diarrhea (60%) and peripheral neuropathy (60%); all grade 1/2. Grade 3/4 AEs occurred in 80% of patients and included decreased neutrophil (45%), platelet (25%) and white blood cell (25%) counts, anemia (25%) and hypophosphatemia (25%). No treatment-related discontinuations or mortality occurred. In evaluable patients ( n  = 18), overall response rate was 44%, and clinical benefit rate was 61%. Median duration of response was 9.2 months; progression-free survival was 7.4 months; overall survival was not reached. Pano-RVd proved generally well-tolerated and demonstrated potential to overcome lenalidomide and/or bortezomib resistance.
ISSN:2044-5385
2044-5385
DOI:10.1038/s41408-021-00407-5