PMID- 33279887 OWN - NLM STAT- MEDLINE DCOM- 20210607 LR - 20210709 IS - 1421-9662 (Electronic) IS - 0001-5792 (Print) IS - 0001-5792 (Linking) VI - 144 IP - 3 DP - 2021 TI - Phase II, Multicenter, Single-Arm, Open-Label Study to Evaluate the Efficacy and Safety of Panobinostat in Combination with Bortezomib and Dexamethasone in Japanese Patients with Relapsed or Relapsed-and-Refractory Multiple Myeloma. PG - 264-274 LID - 10.1159/000508529 [doi] AB - INTRODUCTION: Panobinostat, bortezomib, and dexamethasone combination therapy demonstrated progression-free survival (PFS) benefit over bortezomib and dexamethasone alone in the PANORAMA-1 study in relapsed/refractory multiple myeloma (MM). Here, we present data from a phase II study (NCT02290431) of this combination in Japanese patients with relapsed or relapsed-and-refractory MM. METHODS: Patients received 3-week cycles of 20-mg oral panobinostat (weeks 1 and 2), 1.3-mg/m2 subcutaneous bortezomib (days 1, 4, 8, and 11), and 20-mg oral dexamethasone (day of and the day following bortezomib administration) for a total of 8 cycles (24 weeks; treatment phase 1). Patients with treatment benefit had an option to enter the extension phase to receive 6-week (42-day) cycles of panobinostat (weeks 1, 2, 4, and 5) plus bortezomib (days 1, 8, 22, and 29) and dexamethasone (day of and the day following bortezomib treatment) for 24 weeks. The primary objective was complete response (CR) + near CR (nCR) rate after treatment phase 1 as per the modified European Society for Blood and Marrow Transplantation criteria. RESULTS: Of the 31 patients, 4 (12.9%) completed the treatment and 27 (87.1%) discontinued; 17 (54.8%) entered the extension phase. In total, 24 patients (77.4%) entered the survival follow-up phase and followed until study closure when the last patient was treated for 1 year after treatment phase 1. The CR + nCR rate was 48.4% (90% CI: 33.6-63.2). The overall response rate (CR + nCR + partial response) was 80.6%. The median PFS, duration of response, time to response, and time to progression were 15.3, 22.7, 1.4, and 15.3 months, respectively. All patients experienced adverse events (AEs), with diarrhea (80.6%), decreased appetite (58.1%), and thrombocytopenia (54.8%) being the most frequent, regardless of relationship to the study treatment. Thrombocytopenia (48.4%), fatigue (25.8%), diarrhea (22.6%), neutrophil count decrease (22.6%), platelet count decrease (22.6%), and lymphocyte count decrease (22.6%) were the most frequent grade 3/4 AEs. CONCLUSION: The study met the primary objective with 48.4% CR + nCR rate. The AEs associated with the combination treatment were safely managed using the existing AE management guidelines, including dose interruption/modification and/or supportive medical intervention. This treatment regimen is an effective option with a favorable benefit/risk profile for Japanese patients with relapsed/refractory MM. CI - The Author(s). Published by S. Karger AG, Basel. FAU - Suzuki, Kenshi AU - Suzuki K AD - Department of Hematology, Japanese Red Cross Medical Center, Tokyo, Japan, ken-suzuki@mtb.biglobe.ne.jp. FAU - Sunami, Kazutaka AU - Sunami K AD - Department of Hematology, National Hospital Organization Okayama Medical Center, Okayama, Japan. FAU - Matsumoto, Morio AU - Matsumoto M AD - Department of Hematology, National Hospital Organization Shibukawa Medical Center, Shibukawa, Japan. FAU - Maki, Akio AU - Maki A AD - Novartis Pharma K.K., Tokyo, Japan. FAU - Shimada, Fumika AU - Shimada F AD - Novartis Pharma K.K., Tokyo, Japan. FAU - Suzuki, Kazuyuki AU - Suzuki K AD - Novartis Pharma K.K., Tokyo, Japan. FAU - Shimizu, Kazuyuki AU - Shimizu K AD - Department of Hematology/Oncology, Higashi Nagoya National Hospital, Nagoya, Japan. LA - eng SI - ClinicalTrials.gov/NCT02290431 PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20201204 PL - Switzerland TA - Acta Haematol JT - Acta haematologica JID - 0141053 RN - 69G8BD63PP (Bortezomib) RN - 7S5I7G3JQL (Dexamethasone) RN - 9647FM7Y3Z (Panobinostat) SB - IM MH - Adult MH - Aged MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects/pharmacokinetics/*therapeutic use MH - Bortezomib/*administration & dosage/pharmacokinetics MH - Dexamethasone/*administration & dosage/pharmacokinetics MH - Diarrhea/etiology MH - Drug Administration Schedule MH - Half-Life MH - Humans MH - Japan MH - Kaplan-Meier Estimate MH - Male MH - Middle Aged MH - Multiple Myeloma/*drug therapy/mortality/pathology MH - Neoplasm Staging MH - Panobinostat/*administration & dosage/pharmacokinetics MH - Progression-Free Survival MH - Recurrence MH - Remission Induction MH - Thrombocytopenia/etiology PMC - PMC8259066 OTO - NOTNLM OT - Bortezomib OT - Dexamethasone OT - Multiple myeloma OT - Panobinostat COIS- Kenshi Suzuki received honoraria from Celgene, Takeda, Ono pharmaceutical, Amgen, Novartis, Sanofi, Bristol-Myers Squibb, AbbVie, and Janssen; acted as a consultant for Amgen, Janssen, Takeda, and Celgene; and received research funding from Bristol-Myers Squibb, Celgene, and Amgen. Kazutaka Sunami received research funding from Novartis, GlaxoSmithKline, Janssen, AbbVie, Takeda, Sanofi, Bristol-Myers Squibb, Ono pharmaceutical, MSD, Alexion Pharma, Daiichi Sankyo, and Celgene and received honoraria from Takeda, Bristol-Myers Squibb, Ono pharmaceutical, and Celgene. Morio Matsumoto received personal fee from Bristol-Myers Squibb K.K., Janssen Pharmaceutical Co., Ltd, Celgene Co. Ltd, and Ono Pharmaceutical Co. Ltd. Akio Maki, Fumika Shimada, and Kazuyuki Suzuki are employees of Novartis; Kazuyuki Shimizu has nothing to disclose. EDAT- 2020/12/07 06:00 MHDA- 2021/06/08 06:00 PMCR- 2020/12/04 CRDT- 2020/12/06 20:49 PHST- 2019/12/20 00:00 [received] PHST- 2020/05/02 00:00 [accepted] PHST- 2020/12/07 06:00 [pubmed] PHST- 2021/06/08 06:00 [medline] PHST- 2020/12/06 20:49 [entrez] PHST- 2020/12/04 00:00 [pmc-release] AID - 000508529 [pii] AID - aha-0144-0264 [pii] AID - 10.1159/000508529 [doi] PST - ppublish SO - Acta Haematol. 2021;144(3):264-274. doi: 10.1159/000508529. Epub 2020 Dec 4.