New Standard Myeloma Therapies Making a Big Difference for Patients

Sundar Jagannath, MD

Sundar Jagannath, MD

For patients with multiple myeloma, newly approved therapies have led to impressive gains in terms of both remission and improved quality of life, according to Sundar Jagannath, MD.

“Every time one of these novel agents comes into the treatment of multiple myeloma—if we follow the SEER data—we can actually see that it has an impact on the survival of the patient,” says Jagannath, a professor of Medicine, Hematology and Medical Oncology at Mount Sinai Hospital.

“Moreover, the progression-free survival (PFS) rates are improving. That means a lot of patients are responding to treatment, and they are in remission. When patients are in remission, their quality of life is good, they are more productive, and more patients go to work. These changes are all important, dramatic, and have really changed how patients with multiple myeloma are treated and how they enjoy their lives,” added Jagannath.

The triplet regimen of bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone has made a significant impact, says Jagannath, especially since it became a standard of care for patients with previously untreated multiple myeloma following the phase III randomized SWOG S0777 trial, results of which were presented at the 2015 Annual Meeting of the American Society of Hematology (ASH).

The study showed that bortezomib, lenalidomide, and dexamethasone resulted in a statistically significant and clinically meaningful improvement in PFS and also an increased overall survival (OS) compared with lenalidomide and dexamethasone alone in previously untreated patients with multiple myeloma without intent for immediate autologous stem cell transplantation.

Daratumumab (Darzalex), elotuzumab (Empliciti), and ixazomib (Ninlaro), all approved by the FDA in November 2015 for previously treated multiple myeloma, are also poised to make an impact in the frontline setting. Checkpoint inhibitors have potential in this space as well, says Jagannath.

In a recent interview, Jagannath discussed the importance of the standardization of a 3-drug regimen for newly diagnosed multiple myeloma, how the regimen may evolve going forward, and other novel agents on the horizon.

What advances in newly diagnosed multiple myeloma have made the most impact on the field thus far?

Jagannath: The treatment of multiple myeloma is changing very rapidly. There are many new drugs coming into the field. There was a pivotal trial reported at the last ASH meeting, which, once and for all, said that 3 drugs were better than 2 drugs for all patients. Typically, we recommend a proteasome inhibitor, such as bortezomib or carfilzomib (Kyprolis), lenalidomide, and dexamethasone. This has become the standard of care for newly diagnosed patients.

This standard makes it easier for physicians, because they no longer have to go through a complicated algorithm of a good-risk/poor-risk patient, looking at cytogenetics, FISH (fluorescence in situ hybridization), and so on. What is also important is that the 3-drug regimen not only increased the response rate and depth of response, but there was improvement in the PFS. Surprisingly, it even had an impact on OS. Therefore, choosing the best treatment upfront becomes very important.

Is this standard 3-drug regimen here to stay, or will that evolve also?

The pipeline is very robust, so I am sure that, in a year or so, we may even include different drugs in the frontline combination—especially monoclonal antibodies—such as the anti-CD38 agents daratumumab and elotuzumab.

All of these are being investigated in frontline in randomized trials. We will be eagerly awaiting these results. We will have the findings regarding the combinations of elotuzumab/lenalidomide/dexamethasone, as well as the oral proteasome inhibitor ixazomib with lenalidomide and dexamethasone. Over the next few years, the treatment of the patient with newly diagnosed myeloma will be evolving. One thing that is certain is that 3 drugs will be better than 2.

At this time, are there any patients who should not receive a 3-drug regimen in the upfront setting?

In clinical trials, evidence-based medicine will say that 3 drugs are better than 2. However, there are certain mitigating circumstances in which the choice of therapy will depend on how the patient presents. For patients presenting with renal impairment, there are challenges in using lenalidomide. It may be better to use thalidomide instead.

Likewise, with frail patients, you may not want to use all 3 drugs; you may use a 2-drug approach and dose adjustments may be required. There are circumstances where a 3-drug combination with the same 3 drugs we are recommending now—bortezomib, lenalidomide, and dexamethasone—may not be ideal.

What novel agents or approaches do you see on the horizon?

It is an exciting time. I am especially excited about the use of monoclonal antibodies and immunotherapy in patients with newly diagnosed multiple myeloma. Monoclonal antibodies and novel immunotherapy approaches may overcome mutational burden in the cancer cells, or drug resistance in the cancer cells.

Patients we have traditionally considered as high risk and difficult to treat could potentially have improved outcomes. In this regard, daratumumab and elotuzumab have a lot of potential. Checkpoint inhibitors are always being investigated in the advanced setting. If those trials are positive, they may move into the upfront setting. My feeling is that immunology is poised to play a major role in the treatment of multiple myeloma. The impact is not only going to be in relapsed myeloma; the impact will be felt in patients newly diagnosed with multiple myeloma.