Panobinostat in combination with bortezomib and dexamethasone in multiply relapsed and refractory myeloma; UK routine care cohort
The combination of panobinostat, bortezomib and dexamethasone (PanBorDex) is available as a treatment option for relapsed refractory multiple myeloma (RRMM) based on the PANORAMA-1 trial which investigated this triplet in early relapse. In routine clinical care, PanBorDex is used primarily in later...
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| Published in: | PloS one Vol. 17; no. 7; p. e0270854 |
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| Main Authors: | , , , , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
San Francisco
Public Library of Science
07-07-2022
Public Library of Science (PLoS) |
| Subjects: | |
| Online Access: | Get full text |
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| Summary: | The combination of panobinostat, bortezomib and dexamethasone (PanBorDex) is available as a treatment option for relapsed refractory multiple myeloma (RRMM) based on the PANORAMA-1 trial which investigated this triplet in early relapse. In routine clinical care, PanBorDex is used primarily in later relapses and is commonly administered in attenuated dosing schedules to mitigate the treatment-related toxicity. We set out to evaluate efficacy and safety outcomes with PanBorDex later in the disease course and evaluate the role of attenuated dosing schedules. This was a retrospective evaluation of patients treated in routine clinical practice between 2016-2019 across seven heamatology centres in the UK; patients who received at least one dose of PanBorDex were eligible for inclusion. The dosing schedule of panobinostat (10mg, 15mg or 20mg, twice or three times a week) and bortezomib (0.7mg/m.sup.2, 1mg/m.sup.2 or 1.3mg/m.sup.2 once or twice weekly) was as per treating physician choice. Patients received treatment until disease progression or unacceptable toxicity. The primary outcome is response rates according to IMWG criteria. Key secondary endpoints include progression-free survival (PFS) and overall survival (OS). Other secondary endpoints include rates of adverse events according to CTCAE criteria. In total, 61 patients were eligible for inclusion and received PanBorDex primarily as [greater than or equal to]5.sup.th line of treatment. One third of patients received PanBorDex at full dose, for the remaining two thirds, treatment was given in reduced dose intensities. The overall response rate was 44.2%, including 14.7% very good partial response (VGPR) rates; 68.8% of patients derived clinical benefit with stable disease or better. The median PFS was 3.4 months; non-refractory patients and those who achieved VGPR benefited from prolonged PFS of 11.4 months and 17.7 months, respectively. The median OS was 9.5 months. The triplet was associated with 45% and 18% incidence of grade 3-4 thrombocytopenia and diarrhea, respectively. |
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| Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: N. Maouche: Takeda UK; honorarium, consultancy fees, speaker fees, conference attendance, grant, Celgene; speaker fees, Novartis; speaker fees, Janssen; conference fees, Abbvie; conference fees. B. Kishore: Celgene; consultancy, Takeda UK; conference attendance, BMS; conference attendance, Janssen; conference attendance, Shire; advisory board. Z. Bhatti: None Declared. B. Supratik: None Declared. F. Karim: None Declared. S. Sundararaman: None Declared. F. Collings: Celgene; Speaker fees, Takeda; Speaker fees. B. Tseu: None Declared. H. Leary: None Declared. N. Ryman: None Declared. U. Reddy: None Declared. G. Vallance: Jazz Pharmaceuticals; grant, Takeda UK; grant. J. Kothari: None Declared. K. Ramasamy: Janssen; grant, speaker fees, advisory board, Novartis; advisory board. This does not alter our adherence to PLOS ONE policies on sharing data and materials. |
| ISSN: | 1932-6203 1932-6203 |
| DOI: | 10.1371/journal.pone.0270854 |