Update in Multiple Myeloma – Latest Research, Future Therapies and Hope, Mitul Gandhi, MD, Virginia Cancer Specialists

Multiple myeloma is a hematologic malignancy, with an annual incidence of approximately 32,000 patients in the United States¹, and a median age of onset at 70. It is a cancer of bone marrow plasma cells, which normally function as professional antibody producing cells and are an integral component of the immune system. Manifestations of the disease typically include bone lesions, kidney dysfunction, electrolyte derangements, and lowering of the blood counts. Treatment in the not too distant past principally revolved around intensive combinatorial chemotherapy, which while temporarily lowering disease burden, rarely resulted in persistent remissions. In the modern era, however, rapid response can be realized with a relatively brief course of well tolerated targeted therapy. The most commonly utilized induction regimen in the US uses lenalidomide (Revlimid), bortezomib (Velcade), and dexamethasone (a steroid) and can often be safely administered in patients in their 7^th and 8^th decade of life. Consolidation with an autologous stem cell transplant using a patients own stem cells or maintenance attenuated dose RVD both serve to deepen and extend this initial response.

Meaningful clinical advances have occurred in the last several years, predicated upon intensive basic science research of myeloma biology. This includes refining of risk stratification to more precisely discriminate different subsets of patients based upon molecular and genetic characteristics. Increasing recognition of disease heterogeneity is informing an individualized approach to treatment. Therapeutic advances include: advent of second generation targeted agents- pomalinomide, carfilzomib, ixazomib- which often have better efficacy and narrower toxicity profile than the original compounds; antibody based immunotherapy which hones onto specific molecules on the surface of the myeloma cell causing cell death- daratumumab, elotuzumab, isatuximab; and novel compounds which attack different chokepoints critical to myeloma cell survival- selenixor, venetoclax (still investigational)². Finally, the next iteration of immunotherapy using genetically modified cellular therapy and sophisticated antibodies conjugated to chemotherapy payloads embody the exciting frontier of myeloma research. Early results are promising and these agents are actively being investigated earlier in the disease course.

So, what do we do with this welcome burden of new drugs? The field is actively exploring several critical questions:

First, how do we intelligently combine and sequence these agents in new patients to achieve deep and durable remissions? What combination yields the greatest response in the safest manner?
Second, can we sensitively identify and elimination microscopic disease after intensive initial therapy to potentially avert indefinite therapy?
Third, for patients who develop relapse, what is the optimal combination of novel agents which can recapture remission? What is the role of novel immunotherapueutic approaches in this space?
Finally, can we alter the disease course by intervening early in a patient with “pre-myeloma” such that they never develop symptomatic disease? Whether select patients with smoldering myeloma, a long recognized precursor entity, may be able to avert symptomatic disease with intelligently timed treatment is the subject of national and international investigation.

At Virginia Cancer Specialists we have a robust multiple myeloma program with a large volume of patients, a wealth of clinical expertise, and an active research program with an expanding portfolio of clinical trials. We are members of the Mulitple Myeloma Research Consoritum (MMRC), a national network of leading research institutions whose sole purpose is the advancement of myeloma research. Through our collaboration with MMRC and our partnership with US Oncology, we’re able to bring to our community the latest therapeutic advances and cutting edge clinical trials which helps are patients now, and any future patients we’re asked to serve.