The population of patients with multiple myeloma (MM) who are eligible for therapy has been expanded to asymptomatic patients with certain features under the most recent National Comprehensive Cancer Network (NCCN) guideline (Version 3.2016).
Also, among 7 new drug approvals in 2015 with indications for the treatment of MM, new options for treatment in relapsed/refractory MM include, for the first time, a histone deacetylase inhibitor and 2 monoclonal antibodies—daratumumab and elotuzumab.
The updated guideline was presented by Kenneth C. Anderson, MD, at the NCCN 21st Annual Conference. He started by reviewing changes to the diagnostic criteria for the treatment of MM, which expands the active myeloma category as well as the number of patients eligible for treatment. Previously, eligibility for treatment demanded abnormalities in CRAB (calcium, renal function, anemia, and bone abnormalities) features. “However, that is no longer true,” said Dr Anderson, Director, Multiple Myeloma Center at Dana-Farber Cancer Institute, Boston, MA.
The new definition of active MM in asymptomatic patients, which qualifies such patients for treatment, is as follows:
- Bone marrow plasmacytosis ≥60%
- Abnormal free light chain ratio ≥100 (involved kappa) or <0.01 (involved lambda)
- Focal bone marrow lesions detected by functional imaging
As part of the updated guideline, use of the revised International Staging System that incorporates cytogenetics is recommended for the first time for risk stratification.
Primary treatment options in transplant candidates now include bortezomib/lenalidomide/dexamethasone (category 1) and the oral proteasome inhibitor ixazomib for use in combination with lenalidomide/dexamethasone. Ixazomib has a half-life of 3 to 4 days and requires only once-weekly administration.
“For the first time, we have a triplet consisting entirely of oral medications included as initial treatment,” Dr Anderson said.
He noted that the triplet of bortezomib/lenalidomide/dexamethasone improved complete response (CR) rates (including molecular CR), progression-free survival (PFS), and overall survival compared with lenalidomide/dexamethasone. The recommendation for up-front triplet therapy applies to transplant candidates and very fit nontransplant candidates, he said.
Carfilzomib/lenalidomide and dexamethasone were included in the new guideline as a category 2A (other) front-line treatment based on a phase 1/2 study (Blood. 2012;120:1801-1809).
Maintenance therapy “is a standard of practice” regardless of whether the patient undergoes transplantation, he said. Maintenance regimens are bortezomib, lenalidomide, and thalidomide, with subcutaneous bortezomib every other week. Ixazomib used as a single agent for maintenance improves the depth of response to ixazomib/
lenalidomide/dexamethasone.
In newly diagnosed nontransplant candidates, a new standard of care is continuous lenalidomide/dexamethasone, which was found to extend PFS significantly with a favorable safety profile (N Engl J Med. 2014;371:906-917).
As an addition in the relapsed setting, carfilzomib/lenalidomide/dexamethasone extended PFS by 6 months whether patients had high-risk or standard cytogenetics compared with a doublet of lenalidomide and dexamethasone (N Engl J Med. 2015;372:142-152).
Of the 8 new options for the treatment of previously treated MM, 1 is a histone deacetylase inhibitor (panobinostat) and 2 are monoclonal antibodies.
Panobinostat added to bortezomib and dexamethasone improved median PFS by 4 months and increased rates of CR and near CR compared with bortezomib/dexamethasone in previously treated patients.
The monoclonal antibodies that appear for the first time as options for MM patients who have received prior therapy or have refractory disease are daratumumab and elotuzumab.
Elotuzumab, which targets the antigen SLAMF7, is approved together with lenalidomide and dexamethasone. Daratumumab, which targets CD38, “was approved as a single agent because it achieved about a 30% response rate even in patients whose myeloma was resistant to bortezomib and lenalidomide,” he said.
