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ORLANDO -- The National Comprehensive Cancer Network (NCCN) has designated preferred treatment regimens for multiple myeloma, giving clinicians more specific guidance for managing these patients.

The preferred regimen (category 1) for primary therapy for non-transplant candidates is bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone, reported Shaji Kumar, MD, of the Mayo Clinic in Rochester, Minnesota, at the NCCN annual meeting. Other preferred options are lenalidomide and low-dose dexamethasone, or bortezomib, cyclophosphamide, and dexamethasone.

For multiple myeloma patients who are eligible for stem cell transplantation, the preferred regimen is bortezomib, lenalidomide, and dexamethasone.

Kumar said "other recommended therapies" include:

• Bortezomib/doxorubicin/dexamethasone
• Carfilzomib (Kyprolis)/lenalidomide/dexamethasone
• Ixazomib (Ninlaro)/lenalidomide/dexamethasone

The guideline writers also list as "useful in certain circumstances:"

• Bortezomib/dexamethasone
• Bortezomib/thalidomide/dexamethasone
• Lenalidomide/dexamethasone
• Dexamethasone/thalidomide/cisplatin/doxorubicin/cyclophosphamide/etoposide/bortezomib (VTD-PACE)

The guideline writers cautioned that "Exposure to myelotoxic agents (including alkylating agents and nitrosoureas) should be limited to avoid compromising stem cell reserve prior to stem cell harvest in patients who may be candidates for transplants."

The preferred treatment for maintenance therapy is lenalidomide, Kumar said.

The advantage of these different levels of preferred or recommend regimens is that "it allows us to start to integrate information, such as if two regimens have equal outcomes, but one is 50% cheaper than the other we can make that regimen 'preferred,'" explained Andrew Zelenetz, MD, PhD, at Memorial Sloan-Kettering Cancer Center in New York City.

"We have had levels of evidence that have been around for a long-time," he noted. "But level 2A evidence can be anything from a randomized phase III clinical trial that people don't love to expert opinion. Because there is this big range of possibilities, and there are increasing treatment options, there is this desire to have in all the NCCN guidelines categories of 'preferred,' 'other recommended,' and 'useful in certain circumstances,' which might be the frail patients who can't get any of the standard treatments."

Zelenetz acknowledged that one of the criticisms of the NCCN guidelines has been that it lists too many options. "We have to consider affordability, toxicity, consistency of the evidence. It is an attempt to help the clinician make better decisions ... This prioritizes what the options are."

Kumar and committee members stated that multiple regimens could be considered in treating patients who had undergone previous therapies, and relapsed or became intolerant to treatment. The preferred treatments in these patients are:

• Repeat primary induction therapy if the relapse occurs longer than 6 months after the initial course of treatment
• Bortezomib/doxorubicin/dexamethasone
• Carfilzomib (twice weekly)/dexamethasone
• Carfilzomib/lenalidomide/dexamethasone
• Daratumumab (Darzalex)/bortezomib/dexamethasone
• Daratumumab/lenalidomide/dexamethasone
• Elotuzumab (Empliciti)/lenalidomide/dexamethasone
• Ixazomib/lenalidomide/dexamethasone.

The list of 21 other recommended therapies includes doublets and triplets using bendamustine, bortezomib, carfilzomib, cyclophosphamide, daratumumab as a monotherapy and in combinations, pomalidomide (Pomalyst), elotuzumab, ixazomib, lenalidomide, panobinostat (Farydak).

The guidelines for relapsed disease also lists "useful I certain circumstances:"

• Bendamustine monotherapy
• Dexamethasone/cyclophosphamide/etoposide/cisplatin (DCEP)
• Dexamethasone/thalidomide/cisplatin/doxorubicin/cyclophosphamide/etoposide plus/minus bortezomib.
• High-dose cyclophosphamide