Recently Approved Agents

In 2015, the U.S. Food and Drug Administration approved two agents for the treatment of patients with multiple myeloma (MM): the HDAC inhibitor panobinostat and the selective proteasome inhibitor carfilzomib.

Panobinostat: On February 23, 2015, the U.S. FDA approved panobinostat for the treatment of patients with MM, making it the first histone deacetylase (HDAC) inhibitor approved for this condition. Panobinostat is indicated for patients who have received at least two prior standard therapies – including bortezomib and an immunomodulatory agent – and is to be used in combination with bortezomib and dexamethasone (PBD). The safety and efficacy of the panobinostat combination was demonstrated in a clinical trial of 193 patients with MM who were randomly assigned to receive PBD or bortezomib + dexamethasone (BD) alone; treatment with panobinostat significantly extended progression-free survival by four months. In addition, 59 percent of PBD-treated participants demonstrated response after treatment, compared with only 41 percent in the BD group. Panobinostat does carry a Boxed Warning about severe diarrhea and severe and fatal cardiac events, arrhythmias, and electrocardiogram changes that have occurred in patients receiving the medication.

Carfilzomib: On July 24, 2015, the U.S. FDA approved carfilzomib in combination with lenalidomide and dexamethasone for the treatment of patients with relapsed MM who have received one to three prior lines of therapy. Approval was based on data from the phase III ASPIRE study, which included 792 previously treated patients. Patients treated with carfilzomib plus lenalidomide and dexamethasone had longer progression-free survival, overall and complete response rates than those treated with lenalidomide and dexamethasone alone. The trial also found that the carfilzomib combination group reported superior health-related quality of life. Carfilzomib has been previously approved by the U.S. FDA as a single agent for treatment of MM in patients who have received at least two prior therapies, including bortezomib and an immunomodulatory agent, and in those who have progressed on or within 60 days of the last therapy.


The Myeloma Pipeline

Below is a list of agents currently under investigation for the treatment of multiple myeloma (MM), newly diagnosed MM (NDMM), relapsed/refractory MM (RRMM), or smoldering MM. Information was gathered from ClinicalTrials.gov, as well as the respective drug manufacturers.

MONOCLONAL ANTIBODIES

  • Elotuzumab: anti-SLAMF7 monoclonal antibody for the treatment of patients with RRMM (phase III), NDMM (phase III), or smoldering MM (phase II)
  • Daratumumab: anti-CD38 monoclonal antibody for the frontline treatment of MM (phase III) or the treatment of patients with RRMM (phase III)
  • SAR650984: anti-CD38 monoclonal antibody for the treatment of patients with MM (phase II)

ANTIBODY DRUG CONJUGATES

  • BT062 (indatuximab ravtansine): antibody drug conjugate comprising an anti-CD138 monoclonal antibody (indatuximab) and the cytotoxic agent ravtansine for the treatment of patients with RRMM (phase I/II)

PROTEASOME INHIBITORS

  • Ixazomib: oral 20S proteasome inhibitor for patients with RRMM (phase III)
  • Oprozomib: oral epoxyketone proteasome inhibitor for the treatment of NDMM (phase I/II) or RRMM (phase I/II)
  • Marizomib: oral β-lactone-γ-lactam for the treatment of RRMM (phase I/II)

ALKYLATING AGENTS

  • Melflufen: melphalan-derived prodrug for the treatment of RRMM (phase I/II)

HDAC INHIBITORS

  • Ricolinostat: oral, selective HDAC6 inhibitor for the treatment of RRMM (phase I/II)

CDK INHIBITORS

  • Palbociclib: CDK4/CDK6 inhibitor for the treatment of patients with RRMM (phase II)
  • Dinaciclib: CDK pan-inhibitor for the treatment of patients with RRMM (phase II)

OTHER AGENTS IN THE PIPELINE

  • KPT-330 (selinexor): an oral small molecule inhibitor of CRM1 for the treatment of RRMM (phase II)
  • ABT-199 (veneclotax): selective BCL-2 inhibitor for the treatment of RRMM (phase I)
  • Filanesib: targeted KSP inhibitor for the treatment of RRMM or advanced MM (phase II)
  • Afuresertib: oral AKT inhibitor for the treatment of RRMM (phase I)

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