Building on Research on Immunomodulator Regimens in Relapsed Multiple Myeloma Treatment

Researchers study whether more may be better when treating relapsed/refractory multiple myeloma.

While innovative therapies have helped improve the relative survival rate for patients with multiple myeloma, the disease remains incurable with most patients experiencing repeated relapse and ultimately becoming refractory to treatments. Today, research continues to delve into whether treating relapsed multiple myeloma with combination therapies may be an appropriate option for certain patients. More agents could also result in increased toxicities and patients must be monitored closely.

­At the 54th Annual Meeting of the American Society of Clinical Oncology (ASCO), new data regarding the use of triplet therapy for relapsed multiple myeloma were presented. Now four or more drug combinations are being examined as well. In this interview, Dr. Paul Richardson, the RJ Corman Professor of Medicine at Harvard Medical School and clinical program leader and director of clinical research at the Jerome Lipper Multiple Myeloma Center at Dana-Farber Cancer Institute, discusses the new data presented at this year’s ASCO meeting and how the future of relapsed multiple myeloma treatment could look.

DR. PAUL RICHARDSON

DR. PAUL RICHARDSON FROM DANA-FARBER CANCER INSTITUTE BELIEVES THAT WE WILL CONTINUE TO SEE PROMISING RESULTS FROM COMBINATION THERAPIES FOR RELAPSED/REFRACTORY MULTIPLE MYELOMA.

Why have triplet and quadruplet regimens become more frequently used to treat relapsed multiple myeloma?

“Multiple myeloma is a heterogeneous disease, which means that patients typically have multiple subpopulations of malignant plasma cells with different molecular profiles and characteristics. When patients with multiple myeloma are given a single therapy, some of these subpopulations recede while others may grow. This phenomenon is believed to contribute to treatment resistance and eventual relapse.”

“So the theory that combination therapies provide a multi-pronged attack to target multiple myeloma subpopulations may be a reason why we are seeing more relapsed multiple myeloma patients being treated with combination therapies. Quadruplet regimens are also being investigated for high-risk patients with particularly resistant multiple myeloma.”

How have data presented at this year’s ASCO meeting moved the field forward?

“At ASCO, we saw new data from clinical trials comparing triplet with doublet regimens for relapsed multiple myeloma. Those findings support the idea that if you throw a wider net around the illness early with a triplet, you may achieve greater clinical benefit. At the same time, as we continue to explore new combinations, we are finding more regimens that may be better tolerated by patients.”

Why do many of these combinations include immunomodulators?

“Immunomodulators are an integral part of multiple myeloma treatment in both the newly diagnosed and relapsed/refractory setting. These therapies have numerous effects on tumor cells, the immune system, and the tumor microenvironment which we believe leads to their anti-multiple myeloma activity. In fact, they constitute a foundation for therapy regimens in multiple myeloma.”

“At this year’s ASCO, we saw important new data from trials exploring the interactions between these therapeutic classes in the relapsed setting.”

Although the treatment of relapsed multiple myeloma remains an unmet medical need, we’re making progress. The data presented at ASCO on combination therapies and potential breakthrough approaches like CAR T cell therapy are particularly exciting.

How are researchers taking a more precision-focused approach to treating relapsed multiple myeloma?

“Choosing the most appropriate therapy based on the genetic causes of a disease makes sense but is challenging in multiple myeloma, because the cancer is so genetically unstable. For example, we sequenced the genome of one patient at diagnosis and identified over 5,000 disease-associated mutations. By the time he relapsed, we had found more than 12,000. When you have that number of genetic changes, targeting a single mutation will be unlikely to make much of a difference on its own.”

“To help address this problem, we have to take a modified precision medicine approach. Researchers are studying whether combining backbone agents such as immunomodulators and proteasome inhibitors that have broad success in the disease with more targeted agents and evaluating these combination regimens, and in particular with monoclonal antibodies.”

What are your thoughts on the future of relapsed multiple myeloma treatment following this year’s ASCO meeting?

“Although the treatment of relapsed multiple myeloma remains an unmet medical need, we’re making substantial progress. The data presented at ASCO on combination therapies and potential breakthrough approaches like CAR T cell therapy are particularly exciting. While the FDA approved CAR T cell therapies have already shown promise in other cancers, multiple myeloma is a much tougher nut to crack. So we’ll have to wait and see what happens with these trials in the longer term, but early data are encouraging.”

To learn more about the advances discussed at ASCO 2018, read “ASCO 2018 Preview: Precision Medicine, CAR T Cells and Immunomodulators.”

Dr. Richardson regularly provides input as a paid consultant for Celgene.