Multiple Myeloma: Updates on Diagnosis and Management

Standard-risk patients have similar OS regardless of whether or not CR is achieved and thus can either
be treated with an aggressive approach or a sequential therapy approach. ¹⁶

Transplant-Eligible Patients

All patients should be evaluated for transplant eligibility, because it results in superior progression-free survival (PFS) and OS in patients with MM compared
with standard chemotherapy. Transplant eligibility requirements differ, depending on the transplant center. There is no strict age limit in the U.S. for determining transplant eligibility. Physiological age and factors such as functional status and liver function are often considered before making a transplant decision.

For VA patients, transplants are generally considered in those aged < 65 years, and patients are referred to 1 of 3 transplant centers: VA Puget Sound Healthcare System in Seattle, Washington; Tennessee Valley Healthcare System in Nashville; or South Texas Veterans Healthcare System in San Antonio. ¹⁷ All patients who are transplant eligible should receive induction therapy for 2 to 4 months before stem cell collection. This is to reduce tumor burden, for symptomatic management, as well as to lessen end organ damage. After stem cell collection, patients undergo either upfront ASCT or resume induction therapy and undergo a transplant after first relapse.

Bortezomib Regimens

Bortezomib is a proteasome inhibitor (PI) and has been used as upfront chemotherapy for transplant-eligible patients, traditionally to avoid alkylating agents that
could affect stem cell harvest. It is highly efficacious in the treatment of patients with MM. Two- or 3-drug regimens have been used. Common regimens include bortezomib, cyclophosphamide, dexamethasone; bortezomib, thalidomide, dexamethasone (VTD); bortezomib, lenalidomide, dexamethasone (VRD); bortezomib,
doxorubicin, dexamethasone; as well as bortezomib, dexamethasone. ¹⁸ Dexamethasone is less expensive than VTD or VRD, well tolerated, and efficacious. It is
often used upfront for newly diagnosed MM. ¹⁹ Threedrug regimens have shown to be more efficacious than 2-drug regimens in clinical trials (Table 5). ²⁰

Of note, bortezomib is not cleared through the kidney, which makes it an ideal choice for patients with renal function impairment. A significant potential AE with bortezomib is the onset of peripheral neuropathy. Bortezomib can be administered once or twice weekly. Twice-weekly administration of bortezomib is preferred when rapid results are needed, such as light chain cast nephropathy causing acute renal failure. ²¹

Lenalidomide Plus Dexamethasone

Lenalidomide is a second-generation immunomodulating agent that is being increasingly used as initial therapy for MM. There is currently no data showing superiority of bortezomib-based regimens to lenalidomide plus dexamethasone in reference to OS. Bortezomib-based regimens seem to overcome the poor prognosis associated with t(4;14) translocation and thus should be considered in choosing initial chemotherapy treatment. ²²

Lenalidomide can affect stem cell collection;