Ivan M. Borrello, MD, associate professor of oncology, Johns Hopkins Medicine, discusses treatment for patients with indolent versus aggressive relapsed multiple myeloma.

Whether the relapse is early or late is not as important as whether it's aggressive or indolent and in what setting it occurs, says Borrello. In addition, a patient’s comorbidities must be taken into consideration when selecting treatment.

Since patients with this disease have a median age of 65, a significant number of them will have comorbidities. Notably, if a patient has preexisting neuropathy, proteasome inhibitors such as bortezomib (Velcade) and ixazomib (Ninlaro), may not be the best choice as they can cause neuropathy. Moreover, patients with preexisting cardiac dysfunction may not be best suited to receive carfilzomib (Kyprolis), adds Borrello.

In addition to patient characteristics, the type of response patients had to prior treatment should also be taken into account. This information can help determine whether a patient with relapsed indolent disease could benefit from the addition of 1 drug to their prior regimen, or whether a patient with aggressive relapse would require a complete regimen change, concludes Borrello.

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Ivan M. Borrello, MD, discusses treatment for patients with indolent versus aggressive relapsed multiple myeloma.

Dr. Borello on Treating Indolent Versus Aggressive Relapsed Multiple Myeloma

Ivan M. Borrello, MD, associate professor of oncology, Johns Hopkins Medicine, discusses the current multiple myeloma treatment paradigm.

Multiple myeloma has turned into a chronic disease, according to Borrello. There is an increasing recognition of the concept of clonal evolution, the idea that the disease at the time of diagnosis is much different than the disease at the time of the third or fourth relapse, adds Borrello. Furthermore, the number of available drugs in the treatment of patients with multiple myeloma has significantly increased. These substantial treatment advances have translated into improvements in progression-free survival and overall survival for patients.

Specifically, combinations composed of several different classes of drugs have emerged in this space; they can provide an additive, if not synergistic effect in patients, which can sometimes lead to an improvement in OS, says Borrello. Additionally, some drugs have been shown to molecularly target certain chromosomal abnormalities, Borrello adds. For example, venetoclax (Venclexta) is one such treatment that has demonstrated impressive activity in patients whose disease harbors 11;14 translocation; this is one of the more interesting targeted approaches in the field of myeloma, concludes Borrello.

Ivan M. Borrello, MD, discusses the current multiple myeloma treatment paradigm.

Dr. Borrello Sheds Light on the Multiple Myeloma Treatment Paradigm

Ivan M. Borrello, MD, associate professor of oncology, Johns Hopkins Medicine, discusses the use of selinexor (Xpovio) in the treatment of patients with penta-refractory multiple myeloma.

In July 2019, the FDA granted an accelerated approval to selinexor for use in combination with dexamethasone in the treatment of patients with relapsed/refractory multiple myeloma whose disease is refractory to ≥2 proteasome inhibitors, ≥2 immunomodulatory agents, and a CD38-targeted monoclonal antibody. The drug has a novel mechanism of action, says Borrello. As an oral selective inhibitor of nuclear export (SINE), evaluating the agent in triplet regimens will open a realm of new possibilities for patients, he adds.

Selinexor is a first-in class SINE inhibitor that can be prescribed overnight, says Borrello; this is in contrast to any cellular-based therapy. For example, with CAR T-cell therapy, patients have to go through leukapheresis to have their T cells collected, after which the cells are sent for manufacturing for a period of 2 to 4 weeks. Once the T cells are returned to the institution, patients have to undergo a period of lymphodepletion before they receive the transfusion of T cells.

Ivan M. Borrello, MD

Articles

Dr. Borello on Treating Indolent Versus Aggressive Relapsed Multiple Myeloma

Dr. Borrello Sheds Light on the Multiple Myeloma Treatment Paradigm

Dr. Borrello on Selinexor in Penta-Refractory Multiple Myeloma