Sundar Jagannath, MD
The therapeutic armamentarium for multiple myeloma is ever expanding, says Sundar Jagannath, MD.
“Last year, we had 4 new drugs approved for the treatment of multiple myeloma, including the first-in-class HDAC inhibitor panobinostat (Farydak), 2 monoclonal antibodies— elotuzumab (Empliciti) and daratumumab (Darzalex)—and an oral proteome inhibitor ixazomib (Ninlaro), says Jagannath, a professor of Medicine, Hematology and Medical Oncology at Mount Sinai Hospital. “Now is a very exciting period in multiple myeloma. Whichever way I look at it, the next 3 to 5 years are going to be very significant for myeloma and we will have better solutions for relapsed patients.”
November 2015 was a watershed month for multiple myeloma, as elotuzumab, daratumumab, and ixazomib all received FDA approvals for the disease.
First, the FDA approved daratumumab as a monotherapy for patients with multiple myeloma following at least 3 prior therapies, based on data from 2 open-label clinical trials. The CD38-targeted monoclonal antibody demonstrated a 65% 1-year overall survival (OS) rate and a 29.2% objective response rate (ORR) in the phase II MMY2002 study. In the phase I/II GEN501 study the ORR with single-agent daratumumab was 36%, median progression-free survival (PFS) was 5.6 months (95% CI, 4.2-8.1), and the 1-year OS rate was 77% (95% CI, 58-88) in pretreated patients with relapsed/refractory myeloma.
Secondly, ixazomib was approved in combination with lenalidomide (Revlimid) and dexamethasone as a treatment for patients with multiple myeloma who have received at least 1 prior therapy based on the phase III TOURMALINE-MM1 trial. The trial looked at 722 patients and demonstrated a median PFS of 20.6 months with ixazomib plus lenalidomide and dexamethasone compared with 14.7 months with lenalidomide and dexamethasone alone.
Finally, elotuzumab was approved for use in combination with lenalidomide and dexamethasone for patients with multiple myeloma following the failure of 1 to 3 prior therapies. This approval was based on data from the phase III ELOQUENT-2 trial, in which the 3-drug combination reduced the risk of disease progression by 30% compared with lenalidomide and dexamethasone alone.
In February 2015, the FDA approved panobinostat in combination with bortezomib (Velcade) and dexamethasone for patients with multiple myeloma who received prior treatment with bortezomib and an immunomodulatory agent, based on a prespecified subgroup analysis from the PANORAMA-1 trial. In the analysis, which looked at 193 patients, the median PFS with the panobinostat combination was 10.6 months versus 5.8 months with bortezomib and dexamethasone alone (HR, 0.52; 95% CI, 0.36-0.76).
In addition to the recently approved agents, several novel therapies are currently being investigated in multiple myeloma, including checkpoint inhibitors such as pembrolizumab (Keytruda), CAR T-cell therapy, and vaccines. In an interview with OncLive
, Jagannath discusses which emerging agents he is most excited about, sequencing challenges in multiple myeloma, and the role for personalized medicine in the disease.
OncLive: What upcoming advancements are you most excited about in multiple myeloma?
: There are several new drugs in the pipeline that are going through rapid clinical development. This includes new classes of drugs. At the same time, immuno-oncology is expected to play a major role in multiple myeloma. Also, we now understand that these antibodies that are being approved can be used in combination with other existing drugs effectively and safely.
The future looks even brighter. At the 2015 ASH Annual Meeting, results were presented from a study looking at lenalidomide and dexamethasone with the checkpoint inhibitor pembrolizumab. This combination was able to put patients into remission who were refractory to currently approved agents. This means that the therapeutic armamentarium is going to widen, and there is a possibility that immunotherapy may lead to a cure for myeloma.
In the same way, we are excited that CAR T cells against B-cell maturation antigen are coming into clinical trials in multiple myeloma. There was a CAR T-cell treatment of a single patient case report that was published in The New England Journal of Medicine