For patients with newly diagnosed multiple myeloma, clinicians are moving from doublet to triplet regimens. Cleveland Clinic myeloma specialists, however, have found that most patients can be sufficiently – and less expensively – treated with 2 drugs, reserving the use of the third agent for patients who respond insufficiently to 2.
This is personalized medicine at its best, according to Frederic Reu, MD, senior investigator at the Department of Translational Hematology and Oncology Research, Cleveland Clinic, who codesigned the care path.
“The problem with multiple myeloma research now is that everyone ignores the huge heterogeneity of this disease. No one adjusts the treatment plan according to anything that can be measured,” Reu said in an interview with American Health & Drug Benefits.
At ASH 2014, a pilot study testing this model was presented by Mayur Narkhede, MD, of the Department of Internal Medicine, Cleveland Clinic, who remarked that the triplet of bortezomib, lenalidomide, and dexamethasone (VRD) is preferred by many centers because of its higher rates of response, although there has been no survival difference.
“Since no test predicts who may experience harm from insufficient or excessive therapy, we designed a care path that starts with 2 drugs but adapts treatment early to achieve uniform myeloma control,” Narkhede said.
The researchers noted that 3 drugs convey a higher risk for side effects, especially peripheral neuropathy, and treatment with 3 drugs is considerably more expensive than with 2.
“The VRD regimen has not yet been shown to improve overall survival. If we can limit the toxicity and cost by using 2 drugs, there should be no reason to add a third,” Narkhede said.
Care Path Adds Third Drug Only When Necessary
Reu and a colleague developed the care path for patients not participating in clinical trials. It advises initial treatment with lenalidomide/dexamethasone or bortezomib/dexamethasone, with therapy adjusted depending on the initial response. When patients do not achieve at least a partial response to frontline treatment, clinicians add the other novel agent; cyclophosphamide and liposomal doxorubicin may also be given. The choice between lenalidomide/dexamethasone and bortezomib/dexamethasone is based on insurance coverage and the status of the kidney; patients with evidence of renal disease receive bortezomib/dexamethasone.
In a pilot study of 24 patients, response-adapted therapy allowed disease control with the lenalidomide/dexamethasone or bortezomib/dexamethasone doublet in approximately 60% of patients; subsequent triplets controlled disease in another 30% of patients, and 10% of patients required a fourth drug.
“Response-adapted therapy also avoided progression during induction therapy and, so far, also death during follow-up,” Narkhede reported.
Of the 24 patients, 17 received lenalidomide/dexamethasone initially and 7 received bortezomib/dexamethasone. Of the 17 patients who received lenalidomide/dexamethasone, 12 had a partial response or better. Of the 7 patients who received bortezomib/dexamethasone, 3 had at least a very good partial response. After a median follow-up of 10 months, none of the 24 patients had progressed. The doublet provided disease control in the majority of patients, and only 1 patient developed grade 3 peripheral neuropathy.
Compared with VRD for all patients, which is an emerging trend, doublets reduced the rate of peripheral neuropathy and the cost of treatment. The researchers estimated that the savings for this small cohort exceeded $4000 per cycle.
“Overall survival will be the ultimate assessment of the utility of this approach, but response assessments to date support the ongoing use of the care path,” Narkhede said.
