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New Drug Therapies for Relapsed or Refractory Multiple Myeloma

TOP - August 2017, Vol 10, No 3 - Multiple Myeloma
Meg Barbor, MPH

Anaheim, CA—Although the 5-year survival rate for multiple myeloma is less than 50%, this type of cancer has witnessed a resurgence of drug therapies. Overall, 4 new drugs, each with different mechanisms of action, have been approved by the FDA since 2015, leading to high response rates even in patients with relapsed or refractory disease, said Houry Leblebjian, PharmD, BCOP, Hematology Oncology Clinical Pharmacy Specialist, Dana-Farber Cancer Institute, Boston, at the 2017 Hematology/Oncology Pharmacy Association Annual Conference.

“Progress has been made in multiple myeloma, but there are still unmet needs for relapsed or refractory disease,” she said.

Panobinostat

Panobinostat was approved by the FDA in February 2015, in combination with bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received ≥2 regimens, including bortezomib and an immunomodulatory drug (IMiD).

Panobinostat blocks the enzymatic activity of histone deacetylases (HDACs) and is the only HDAC inhibitor approved for multiple myeloma.

“Administration is easier for patients, because it’s an oral regimen,” said Dr Leblebjian, who noted that panobin­ostat is efficacious in combination with proteasome inhibitors and IMiDs. “Nevertheless, bortezomib and panobin­ostat may have some overlapping tox­icities, so it’s possible that carfilzomib is a better proteasome inhibitor partner.”

Gastrointestinal toxicity, hematologic toxicity, and fatigue can be mitigated by dosing panobinostat every alternate week, Dr Leblebjian reported.

Daratumumab

Daratumumab received FDA approval in November 2015, as monotherapy for the treatment of patients with relapsed or refractory multiple myeloma who have received ≥3 therapies, including an IMiD and a proteasome inhibitor, or patients who are double-refractory to a proteasome inhibitor and an IMiD.

In November 2016, daratumu­mab received a new indication, in combination with bortezomib and dexamethasone or with lenalidomide and dexamethasone, for the treatment of patients with relapsed or refractory disease who have received ≥1 therapies.

Daratumumab demonstrated a 63% reduction in the risk for disease progression or death when continued with bortezomib and dexamethasone in the POLLUX trial. The most common toxicities were fatigue, nausea, back pain, cough, pyrexia, upper respiratory tract infection, and infusion reactions.

“Infusion reactions were most likely with first or second dose, but the use of montelukast can reduce the severity of these issues,” said Dr Leblebjian, who noted that daratumumab combines well with other antimyeloma agents because of minimal overlapping toxicities. 


Ixazomib

Ixazomib was approved by the FDA in November 2015, in combination with lenalidomide and dexamethasone, for the treatment of patients with multiple myeloma who have received ≥1 therapies. Ixazomib is currently the only oral proteasome inhibitor approved by the FDA for the disease.

“Weekly administration is convenient, but patient adherence can be an issue,” said Dr Leblebjian, who recommended the use of patient diaries and reminders to stick to a schedule.

There were no reports of peripheral neuropathy with ixazomib, and nausea can be mitigated with antiemetic premedication. Although ixazomib is not approved for first-line therapy, there is “high potential” for combining ixazomib with other regimens, she noted.

Elotuzumab

Elotuzumab was approved by the FDA in November 2015, in combination with lenalidomide and dexamethasone, for the treatment of patients with multiple myeloma who have received 1 to 3 therapies.

Elotuzumab does not have clinical activity as monotherapy, but is effective when used in combination with lenalidomide and dexamethasone, said Dr Leblebjian. In addition, a low incidence of infusion reactions and other adverse events make it an attractive drug for combination therapies. It is also easy to administer in the long-term setting, she added.

“Many different treatment strategies are currently in clinical trials. Nevertheless, all patients inevitably relapse, and drugs with different therapeutic targets are needed to overcome drug resistance,” she concluded.

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Last modified: September 9, 2019