Chapter 5 – Treatment of relapsed multiple myeloma

Contributor: Michel Delforge

3 – To switch or re-treat

Once the decision to treat has been taken, it is recommended to consider whether the patient is a candidate for a clinical trial in that particular relapse setting. If not, then the second question should be whether retreatment with a previous regimen or a switch to another drug class is to be preferred. With the introduction of several new drugs and combinations for relapsed myeloma a therapeutic switch will mostly be chosen, but retreatment can be a valuable option for selected patients or at specific disease phases. The decision to switch or retreat should be guided by the response duration and the tolerability of that particular previous regimen. An early relapse is defined as disease recurrence within 6–12 months after treatment discontinuation and requires a drug class switch, whereas after longer response durations one can consider retreatment [12]. The cut-off of 6–12 months is rather arbitrary and we propose to consider retreatment if the response duration was longer than the average time reported in clinical trials for that particular regimen, and no serious toxicity issues occurred. According to their label, the immunomodulatory drugs (IMiDs) lenalidomide and pomalidomide are given until progression or unacceptable toxicities. Therefore, retreatment with IMiDs is not routine practice; although a lenalidomide-based triplet can be considered for patients having received lenalidomide-dexamethasone for a limited time period at diagnosis [13]. Retreatment relates more to bortezomib [14] or to high-dose chemotherapy followed by autologous stem cell transplantation (ASCT).

According to local guidelines, single or tandem autograft remain the standard of care for frontline treatment of MM patients up to the ages of 65 or 70 years. However, ASCT at relapse also remains feasible for many patients.

A large survey from the International Center for Blood and Marrow Transplant Research (CIBMTR) reported that PFS and OS were significantly better with a remission duration of at least 3 years after the first ASCT [15]. Compared with weekly oral cyclophosphamide for 3 months, salvage ASCT after conditioning with melphalan 200 mg/m2 resulted in a significantly longer PFS [16]. Nevertheless, the use of highly effective combination regimens at relapse make the added value of ASCT less clear, particularly in the absence of data from randomized trials. A successful stem cell collection can still be possible at relapse, but we recommend collecting upfront sufficient stem cells for two autografts if a tandem transplant or salvage transplant at relapse is taken into consideration.