Evidence of long-term disease control with panobinostat maintenance in patients with relapsed multiple myeloma

Ocio, Enrique M.; Dávila, Julio C.; Caballero, Juan-Carlos; Alonso, Sara; Calle, Verónica González De La; Gazi, Lucien; Opio, Socrates; Jiménez, Mónica; Miguel, Jesús F. San; Mateos, María‐Victoria

doi:10.3324/haematol.2015.124164

Cited by 10 publications

(4 citation statements)

References 12 publications

(4 reference statements)

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“…77 There are minimal data in the posttransplant maintenance setting, although a series of cases has been reported using panobinostat as a maintenance drug in patients with relapsed disease. 78 …”

Section: Monoclonal Antibodiesmentioning

confidence: 99%

Posttransplant maintenance therapy in multiple myeloma: the changing landscape

Sengsayadeth

Malard

Savani

et al. 2017

Blood Cancer Journal

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Transplant-eligible patients with multiple myeloma (MM) now have extended survival after diagnosis owing to effective modern treatment strategies that include new agents in induction therapy, autologous stem cell transplant (ASCT), consolidation therapy and posttransplant maintenance therapy. Standard of care for newly diagnosed, fit patients includes ASCT and, often nowadays, posttransplant maintenance. Several large studies have shown the efficacy of maintenance with thalidomide, lenalidomide and bortezomib in the treatment scheme of MM with regards to prolonging progression-free survival and, to a lesser degree, overall survival. Herein we discuss the data currently available to support the use of maintenance therapy in patients after ASCT as well as the newer available agents that may be a part of its changing landscape in the years to come.

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Section: Monoclonal Antibodiesmentioning

confidence: 99%

Posttransplant maintenance therapy in multiple myeloma: the changing landscape

Sengsayadeth

Malard

Savani

et al. 2017

Blood Cancer Journal

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“…Panobinostat consolidation was associated with an improvement in disease response in 48% of an intention‐to‐treat population with a suboptimal response following induction and ASCT. We hypothesise, based on the kinetics of response in the present study and case reports from Spanish investigators describing prolonged disease control with panobinostat maintenance 22 that extended exposure to panobinostat may be required for maximal anti‐MM effect. It is therefore not surprising that when used as a single agent in patients with advanced MM and an associated aggressive disease phenotype the observed anti‐MM impact was modest 12 …”

Section: Discussionmentioning

confidence: 72%

Phase II trial of single‐agent panobinostat consolidation improves responses after sub‐optimal transplant outcomes in multiple myeloma

et al. 2020

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Summary Panobinostat is a pan‐deacetylase inhibitor that modulates the expression of oncogenic and immune‐mediating genes involved in tumour cell growth and survival. We evaluated panobinostat‐induced post‐transplant responses and identified correlative biomarkers in patients with multiple myeloma who had failed to achieve a complete response after autologous transplantation. Patients received panobinostat 45 mg administered three‐times weekly (TIW) on alternate weeks of 28‐day cycles commencing 8–12 weeks post‐transplant. Twelve of 25 patients (48%) improved their depth of response after a median (range) of 4·3 (1·9–9·7) months of panobinostat. In responders, T‐lymphocyte histone acetylation increased after both three cycles (P < 0·05) and six cycles (P < 0·01) of panobinostat when compared to baseline, with no differences in non‐responders. The reduction in the proportion of CD127+CD8+ T cells and CD4:CD8 ratio was significantly greater, after three and six cycles of panobinostat compared to pre‐transplant, in non‐responders when compared to responders. Whole marrow RNA‐seq revealed widespread transcriptional changes only in responders with baseline differences in genes involved in ribosome biogenesis, oxidative phosphorylation and metabolic pathways. This study confirmed the efficacy of panobinostat as a single agent in multiple myeloma and established acetylation of lymphocyte histones, modulation of immune subsets and transcriptional changes as pharmacodynamic biomarkers of clinical benefit.

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“…Panobinostat is an FDA-approved chemotherapy agent used in the treatment of multiple myeloma[86, 87]. A pilot eradication clinical trial in Denmark by Rasmussen et al enrolled 15 patients to receive 20mg of panobinostat three times per week during weeks 1, 3, 5 and 7 of an eight week study[40].…”

Section: First Do No Harm: Clinical Trial Outcomesmentioning

confidence: 99%

HIV-1 Eradication: Early Trials (and Tribulations)

Spivak

Planelles

2016

Trends in Molecular Medicine

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Antiretroviral therapy (ART) has rendered HIV-1 infection a manageable illness for those with access to treatment. However, ART does not lead to viral eradication due to the persistence of replication-competent, unexpressed proviruses in long-lived cellular reservoirs. The potential for long-term drug toxicities and the lack of access to ART for most people living with HIV-1 infection have fueled scientific interest in understanding the nature of this latent reservoir. Exploration of HIV-1 persistence at the cellular and molecular level in resting memory CD4+ T cells, the predominant viral reservoir in patients on ART, has uncovered potential strategies to reverse latency. Here, we review recent advances in pharmacologically-based ‘shock and kill’ HIV-1 eradication strategies, including comparative analysis of early clinical trials.

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Evidence of long-term disease control with panobinostat maintenance in patients with relapsed multiple myeloma

Cited by 10 publications

References 12 publications

Posttransplant maintenance therapy in multiple myeloma: the changing landscape

Posttransplant maintenance therapy in multiple myeloma: the changing landscape

Phase II trial of single‐agent panobinostat consolidation improves responses after sub‐optimal transplant outcomes in multiple myeloma

HIV-1 Eradication: Early Trials (and Tribulations)

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