Treatment of Multiple Myeloma

Patients should be referred to a transplant center to determine transplant eligibility. ( EB , H , H , M )

Chronologic age and renal function should not be the sole criteria used to determine eligibility for stem cell transplantation (SCT). ( EB , H , H , M )

The optimal regimen and number of cycles remain unproven. However, at least 3-4 cycles of induction therapy including an immunomodulatory drug, proteasome inhibitor and steroids is advised prior to stem cell collection. ( EB , H , H , M )

Upfront transplant should be offered to all transplant-eligible patients. Delayed initial SCT may be considered in select patients. ( EB , H , B , S )

Agents associated with stem cell toxicity, such as melphalan and/or prolonged immunomodulatory drugs exposure (more than 4 cycles), should be avoided in patients who are potential candidates for SCT. ( EB , H , H , M )

Ample stem cell collection (sufficient for more than one SCT) should be considered upfront, due to concern for limited ability for future stem cell collection after prolonged treatment exposure. ( EB , H , H , M )

The level of minimal response required to proceed to SCT is not established for patients receiving induction therapy – patients should be referred for SCT independent of depth of response. ( EB , H , H , M )

High-dose melphalan is the recommended conditioning regimen for Auto SCT. ( EB , H , B , S )

Tandem autologous SCT should not be routinely recommended. ( EB , L , B , M )

Salvage or delayed SCT may be used as consolidation at first relapse for those not choosing to proceed to transplant initially. ( EB , H , H , M )

Allogeneic transplant for multiple myeloma is not routinely recommended but may be considered in select high risk patients or in the context of a clinical trial. ( EB , H , B , M )

Consolidation therapy is not routinely recommended but may be considered in the context of a clinical trial. For patient’s ineligible or unwilling to consider maintenance therapy, consolidation therapy for at least 2 cycles may be considered. ( EB , H , H , M )

Lenalidomide maintenance therapy should be routinely offered to standard risk patients starting at approximately day 90-110 at 10-15 mg daily until progression. A minimum of 2 years of maintenance therapy is associated with improved survival, and efforts to maintain therapy for at least this duration are recommended. ( EB , H , B , S )

For patients intolerant of or unable to receive lenalidomide, bortezomib maintenance every 2 weeks may be considered. ( IC , H , H , M )

For high-risk patients, maintenance therapy with a proteasome inhibitor +/- lenalidomide may be considered. ( IC , H , H , M )

There is insufficient evidence to make modifications to maintenance therapy based on depth of response, including minimal residual disease (MRD) status. ( IC , H , H , W )

The quality and depth of response should be assessed by IMWG (International Myeloma Working Group) criteria. ( EB , H , B , S )

The goal of initial therapy for transplant eligible patients should be achievement of the best depth of remission. MRD negative status has been associated with improved outcomes, but it should not be used to guide treatment goals outside the context of a clinical trial. ( EB , H , H , S )

It is recommended that depth of response be assessed with each cycle. Frequency of assessment once best response is attained or on maintenance therapy may be assessed less frequently but at minimum every 3 months. ( EB , H , B/H , )

Whole-body low dose CT scan has been shown to be superior to skeletal survey done with plain x-rays and is the preferred method for baseline and routine bone surveillance. FDG-PET/CT and/or MRI may be used as alternatives at baseline. They may also be used in select situations (e.g. risk stratifying smoldering myeloma, for monitoring response of non-secretory and oligosecretory myeloma and if CT or skeletal survey is inconclusive). ( EB , H , H , S )