Mayo Clinic Recommendations for Myeloma Therapy at First Relapse

BY ERIC HANSEN In a major review of treatment options and outcomes, a group of myeloma specialists from the Mayo Clinic developed guidelines for myeloma patients who are experiencing their first, second or third relapse.  This review, 21 pages long, gives detailed analyses of each of the six classes of drugs for the treatment of myeloma, and describes how and when to use each of them.  It also recommends a second ASCT for those who responded well to their first stem cell transplant, either with or without maintenance. The choices we have are vastly improved from a few years ago, but this means we have more factors to consider in choosing the best combinations of treatment.  It is also even more important that we weigh our general health and fitness, type of myeloma, response to previous treatments, and quality of life issues in deciding which way to go when relapse occurs. This review incorporates data from studies and analyses of myeloma patient responses to the newest treatment options and combinations from all over the world; and is filled with critical and useful information regardless of where we are on our myeloma journey. In this review, the first consideration is the array of drugs and treatments that have come on line in the last two years.  There are now drugs that offer six mechanisms of action against myeloma.  There are also multiple drugs in each class, each with its own advantages and risks.  This presents doctors with complex decisions for each patient, particularly at relapse. As stated in the review (principle author Mayo’s Dr. David Dingli):

“………the {treatment of myeloma} has witnessed a sea of change with the development of many novel therapeutic agents, including immunomodulatory drugs (IMiDs) such as lenalidomide and pomalidomide; proteasome inhibitors (PIs) including bortezomib, carfilzomib, and ixazomib; monoclonal antibodies (MAbs) including daratumumab and elotuzumab; and histone deacetylase inhibitors such as panobinostat that have continued to improve overall survival in patients with this disease.  The availability of so many novel agents has led to the development of a multitude of viable treatment options that have also altered the paradigm of therapy.”

While this seems daunting and almost impossible to sort out, not only for us as patients, but for our doctors as well, the Mayo group in its review provided specific recommendations to consider, based on the best trial results and analysis to date. For example, the review states that all patients who are relapsing after initial treatment (usually an autologous stem cell transplant (ASCT)-- with or without maintenance therapy) should be given a new evaluation, an updated FISH test, and disease staging, as the first steps in guiding treatment decisions.

“The major determinants of the best therapeutic options are (1) the general state of health of the patient; (2) the nature of the relapse-whether it is indolent or aggressive; (3) the agents used for previous therapy as well as the quality (depth) and duration of the response to that therapy; and (4) FISH data on the relapsed bone marrow. Information about previous adverse effects related to each drug used is also important to help in the selection of therapy for relapsed disease. There is increasing evidence that deeper responses are associated with better PFS if not overall survival.   Therefore, it is our approach to try and achieve as deep a response as possible after the first relapse in an attempt to favorably affect overall survival, keeping in mind the presence of comorbidities, the quality of life of the patient, including the need for frequent and perhaps lengthy clinical visits, and the expense of therapy. Given the superiority of triple combination therapy for both newly diagnosed and relapsed multiple myeloma, we also generally prefer triple combination therapy for relapsed disease, as long as the patient can tolerate the therapy.”

So, given all this background, what exactly can we do at relapse? The Mayo group gives the following specific recommendations to consider:

“…… Patients who relapse while receiving therapy should be treated with a 3-drug regimen. Fit patients should be treated with a daratumumab- or carfilzomib-based regimen. Frail patients should be treated with a daratumumab- or ixazomib-based regimen. Patients may also be considered for a salvage or second ASCT if they are eligible.  Patients experiencing relapse of their disease that is resistant to lenalidomide should be treated with DVd, whereas patients experiencing relapse of the disease that is resistant to bortezomib should be treated with DRd. Patients who fail daratumumab can be considered for elotuzumab-based therapy.”

The Mayo team’s review provides a great deal more detail, and references dozens of clinical trials and published studies in support of their findings.  It can be accessed in its’ entirety at: https://www.mayoclinicproceedings.org/article/S0025-6196(17)30028-9/fulltext