Treatment Options and Course of Action in Relapsed Multiple Myeloma

In this interview we discuss how relapse in multiple myeloma manifests and treatment options for relapsed/refractory patients.

Nina Shah, MD

As part of our coverage of the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 2–6 in Chicago, we are joined by Nina Shah, MD, a hematologist at the University of California, San Francisco, who specializes in the treatment of multiple myeloma. At the meeting, Dr. Shah discussed the different types of ways that patients experience relapse, as well as treatment options for relapsed and refractory multiple myeloma.

-Interviewed by Anna Azvolinsky

Cancer Network: What is the typical first-line course of therapy for multiple myeloma?

Dr. Shah: First, thank you so much for having me. The course and treatment of multiple myeloma has changed dramatically over the past 15 years and I am happy to say that we are getting patients to live longer and actually go back to their regular quality of life after treatment. But it is still a challenge to treat at relapse. In patients who are newly diagnosed, we tend to employ, for fit patients, triplet therapy that includes a combination of bortezomib, lenalidomide, and dexamethasone, or some clinicians like to use bortezomib, cyclophosphamide, and dexamethasone. We are able to give this therapy as an outpatient treatment for several cycles, usually 3 to 6 cycles, and that depends on preference and how the patient is doing. We have seen response rates over 70% to 80% with triplet therapy and even higher in some studies. This has been very encouraging because it allows patients to not only respond but to get a deeper response.

Traditionally, for fit patients, we then often consolidate the treatment with an autologous stem cell transplant. We have been referring more and more patients to this because we found that patients who have myeloma are fitter than we think and are able to undergo this procedure. This involves giving high-dose chemotherapy, usually melphalan, and then we rescue the patient with their autologous stem cells. About 3 months after the patient has recovered, many of us have started to employ maintenance lenalidomide, which was recently approved for this indication, and has been able to expand the progression-free survival for these patients.

Cancer Network: What are the ways that relapse manifests itself? Are there different biological types of relapse that can be detected in the clinic?

Dr. Shah: Yes. I think relapsed myeloma or progressed myeloma is a very confusing area because it is obvious when a patient has a significant relapse; for example, if they have a new anemia or a new bone lesion or new renal failure. But since many of us are watching the myeloma closely, particularly since patients are on maintenance therapy, we often see a biochemical relapse or progression. It is very important to distinguish all of these because they can change when you would treat. But, simply put, if you are in a complete response and you have a reappearance of this M protein, which is our biomarker for myeloma disease burden, if it’s at a low level and the bone marrow is not involved and there is no other evidence of any other bone lesions, new renal failure, or anemia, you can actually watch the patient for a while.

Similarly, progression can manifest as biochemical progression; if the patient had a low, but stable, level of M protein, but then had an increase while on maintenance, that can be anxiety provoking because you are just watching the patient. The official definition of progression is a 25% increase, or an absolute value of 0.5 grams per deciliter if you are talking about the serum. When you see this, it doesn’t necessarily mean that you have to treat the patient. Although, as this number gets closer to an absolute number of 1, that is when you have to treat. This requires close follow-up. If there is any progression with a concurrent clinical manifestation-again, a new anemia, a calcium or bone lesion, or new plasmacytomas-then this pushes us to treat. But I would say that even though this is the official doctrine, many of us do treat before this point because we don’t want to lose the patient in between visits.

Cancer Network: How do you decide on a course of action? You mentioned both monitoring and therapy for patients who have started to relapse after therapy.

Dr. Shah: That is a great question because it can differ from patient to patient. The first thing that you have to consider is how the patient looks to you. Some patients will be looking very healthy in the office because they don’t even know that they have progressed, and other patients will have significant pain that needs to be addressed. All of these factors are what you use to make your decision for the next course of action. Then the second thing that you have to think about is what they have already received. For example, if a patient has already received bortezomib, lenalidomide, and dexamethasone before their transplant, you may consider re-treating them if they did very well on that combination, or you may change the course. This decision is provider dependent, but either one of those is not wrong. After a patient progresses, you may choose to re-treat with bortezomib, lenalidomide, and dexamethasone, and many patients do respond a second time. If you are hesitant, you may change that and give them a newer agent, for example, carfilzomib, which is a newer proteasome inhibitor.

Cancer Network: Lastly, is there something new we have learned about the course of relapse in the last few years that is helping to change the way we care for multiple myeloma patients, or have new targets been identified for treatment?

Dr. Shah: Thankfully, there have been lots of new developments in myeloma. One thing that is on the horizon that I am hoping we will all have soon is immunotherapy. The reason we are able to use that is because we now know more about myeloma and the immune system. We know that myeloma is targetable by the immune system with anti-CD30 antibodies or CAR T cells, against the BCMA antigen on the surface of myeloma cells. The other thing we’ve learned is that a myeloma patient’s immune system is pretty exhausted because it has been going through so much treatment. If we could jump start the immune system with a drug that inhibits PD-1 or PD-L1, we could have some improved responses. The combination of pomalidomide, pembrolizumab, and dexamethasone was published as a positive finding this past year. I think that there are new horizons based on the fact that we better understand what myeloma looks like and how the immune system is interacting with myeloma, so we can harness both of these to get newer therapies.

Cancer Network: Thank you so much for joining us today, Dr. Shah.

Dr. Shah: Thank you.

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