Tremendous advances have recently occurred in the field of multiple myeloma (MM) treatment, but more novel approaches are under investigation.
Looking ahead to the 59th American Society of Hematology (ASH) Annual Meeting, Cancer Therapy Advisor asked Shaji Kumar, MD, professor of medicine and hematologist at the Mayo Clinic in Rochester, Minnesota, to share his thoughts about where we are now and where we are going regarding promising data and novel approaches for MM treatment.
Cancer Therapy Advisor (CTA): What are some exciting recent advances in the treatment of MM that are now US Food and Drug Administration (FDA)-approved and available in the clinic?
Dr Kumar: One of the major advances in the treatment of multiple myeloma in the recent past has been the introduction of monoclonal antibodies. In particular, daratumumab, an antibody directed against CD38 on MM cells has been quite effective as a single agent, and in combination has led to deep responses and long duration of response in patients with newly diagnosed and relapsed disease.
The results with immunomodulatory imide drug (IMiD) combinations have been quite striking, leading to minimal residual disease (MRD) negativity in patients with relapsed and refractory myeloma. Elotuzumab is another monoclonal antibody that targets SLAMF7, another antigen that appears to be relatively specific to myeloma cells. In combination with lenalidomide it has been effective in the treatment of relapsed disease.
Ixazomib is the first oral proteasome inhibitor in the clinic, and given the importance of proteasome inhibition in the treatment of newly diagnosed and relapsed myeloma, this drug allows for longer duration of therapy with less toxicity, especially peripheral neuropathy, without loss of efficacy.
CTA: What have been some challenges (if any) with implementing these new therapies?
Dr Kumar: Overall, these drugs have been incorporated into routine practice fairly easily. Management of infusion reactions certainly remains an initial challenge. These reactions are fairly common with the first infusion, in particular with daratumumab, but they do not typically recur. Treatment with daratumumab can be associated with difficulties in cross-matching red cells should the patient needed the transfusion. Specific assays have been developed to overcome this problem.
The presence of the antibody can sometimes interfere with sensitive assays used for detection of monoclonal protein. The long duration of infusion can create logistical challenges for the treatment centers and can also be an inconvenience for patients, especially those who continue to work full-time. Many of these challenges are being worked on, specifically with the introduction of subcutaneous daratumumab, which can allow for more rapid administration. Finally, the high cost of many of these therapies continues to be a big challenge in the management of patients with myeloma.