Thomas G. Martin, MD
Emerging treatments continue to shift the paradigm in multiple myeloma, including those designed to improve the quality of life for these patients.
For example, the January 2017 FDA approval of denosumab (Xgeva) for the prevention of skeletal-related events (SRE) in multiple myeloma can have an impact on patients with renal insufficiency. In the phase III 482 study, denosumab demonstrated noninferiority to zoledronic acid at delaying time of SRE in patients (HR, 0.98; 95% CI, 0.85-1.14; P
The median time to first on-study SRE was similar between the treatments, at 22.83 months with denosumab versus 23.98 months with the bisphosphonate zoledronic acid. The median progression-free survival (PFS) was 10.7 month higher in the denosumab arm (HR, 0.82; 95% CI, 0.68-0.99; P
Additional systemic agents—some of which were discussed during the 2017 ASH Annual Meeting—are also moving through the pipeline, including venetoclax (Venclexta) and isatuximab.
In an interview during the 2017 OncLive®
State of the Science SummitTM
on Hematologic Malignancies, Thomas G. Martin, MD, clinical professor of medicine, Adult Leukemia and Bone Marrow Transplantation Program, associate director of the Myeloma Program, co-leader, Hematopoietic Malignancies Program, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, discussed emerging advancements in the treatment landscape of multiple myeloma.
OncLive®: Can you discuss the recent FDA approval of denosumab?
: I am excited that denosumab has just received FDA approval for the treatment of patients with plasma cell disorders. Bone disease is a significant complication in multiple myeloma. We had several bisphosphonates, [specifically] pamidronate and zoledronic acid, that have proved efficacious in multiple myeloma, and now there is a third agent.
The major advantage of denosumab over the other agents is it is less nephrotoxic, which is a significant problem in patients with multiple myeloma. This adds to the armamentarium to strengthen bones in patients with myeloma, especially in those patients who have renal insufficiency.
What did you focus on in your presentation on multiple myeloma?
We have made many advancements in patients with multiple myeloma. However, even though we are getting better response rates for all kinds of regimens that we are using, all patients still relapse. When it comes to relapse, we must think about several factors before therapy is started. There are patient- and disease-related factors.
Regarding patient-related factors and choosing therapy, it is important to consider age, performance status, and how robust patients are. Additionally, it is important to know whether they have other toxicities, such as those that are kidney, liver, or cardiac related.
There are certain regimens that are favored for patients who have renal toxicity. For instance, lenalidomide (Revlimid) is excreted in the kidneys and perhaps there is more toxicity in patients who have renal insufficiency, especially if the dose is not reduced. This needs to be taken into consideration.
There are also disease-related factors, such as determining if it is the first or second relapse, or if they have a refractory relapse, as well as the pace of relapse. There are some patients who relapse very fast where they are doubling the time to weeks or a few months. We need to be aggressive when determining their initial therapy.
On the other hand, we have patients who have a biochemical relapse. In those patients, we have the options of using a better tolerated and less potent regimen. We can also use one drug first and add a second drug if it is well tolerated, and then add a third drug, if needed.
The treatment of [patients with] relapsed myeloma is an art with many different strategies to use. We usually break up patients with relapsed myeloma into 2 groups, including patients who relapse early and those who have had 1 to 3 prior lines of therapy and relapse later.
In the early-relapsed group, the last 2 to 5 years have had many randomized trials showing that triplets are better than doublets. The triplets that have shown an advantage include carfilzomib (Kyprolis), lenalidomide, and dexamethasone; elotuzumab (Empliciti), lenalidomide and dexamethasone; ixazomib (Ninlaro), lenalidomide, and dexamethasone; and daratumumab (Darzalex), lenalidomide, and dexamethasone.
Additionally, triplets with antibodies plus proteasome inhibitors are quite good. In one large trial, it was determined that carfilzomib given at a higher dose of 56 mg/m2 is better than bortezomib (Velcade) in terms of PFS.