Omar Nadeem, MD, clinical director, Myeloma Cellular Therapies Program, physician, Dana-Farber Cancer Institute, instructor of medicine, Harvard Medical School, discusses the integration of isatuximab-irfc (Sarclisa) in relapsed/refractory multiple myeloma.

Isatuximab is a CD38-directed monoclonal antibody that is FDA approved for use in various combinations for patients with relapsed/refractory multiple myeloma, says Nadeem. However, CD38-directed antibodies are being evaluated in earlier lines of therapy, including the frontline setting, for patients with multiple myeloma, Nadeem explains.

Patients with multiple myeloma are often refractory to a CD38-directed antibody in their first or second relapse, so how patients will respond to retreatment with a CD38-directed antibody remains unknown, Nadeem says. As such, that unknown hinders the utility of isatuximab-based combinations in practice, adds Nadeem. 

Currently, high rates of deep responses and good tolerability have been observed with isatuximab in combination with pomalidomide (Pomalyst) and dexamethasone, as well as with carfilzomib (Kyprolis) and dexamethasone, Nadeem explains. Whether isatuximab is superior to daratumumab (Darzalex) remains unknown, but having 2 options for these patients is welcome, concludes Nadeem.

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Omar Nadeem, MD, discusses the integration of isatuximab-irfc in relapsed/refractory multiple myeloma.  



Dr. Nadeem on the Integration of Isatuximab in Relapsed/Refractory Multiple Myeloma 

Omar Nadeem, MD, clinical director, Myeloma Cellular Therapies Program, physician, Dana-Farber Cancer Institute, instructor of medicine, Harvard Medical School, discusses the emergence of quadruplet regimens in multiple myeloma.

Monoclonal antibodies, such as daratumumab (Darzalex), have begun to be incorporated into the frontline treatment of patients with multiple myeloma, says Nadeem.

Historically, triplet combinations demonstrated superiority to doublets in clinical trials for patients with newly diagnosed multiple myeloma, Nadeem says. Now, findings from the phase 3 CASSIOPEIA trial (NCT02541383), which evaluated daratumumab, bortezomib (Velcade), thalidomide (Thalomid), and dexamethasone, as well as the phase 2 GRIFFIN trial (NCT02874742), which evaluated daratumumab, lenalidomide (Revlimid), bortezomib, and dexamethasone, have demonstrated superiority with 4-drug regimens vs their 3-drug counterparts in the setting of transplant-eligible multiple myeloma, Nadeem says.

Notably, quadruplet therapies have demonstrated high rates of stringent complete responses and minimal residual disease negativity, as well as improved progression-free survival and overall survival, compared with triplet therapies in this patient population; however, more mature data are needed for these therapies to become standard frontline options, concludes Nadeem.

Omar Nadeem, MD, discusses the emergence of quadruplet regimens in multiple myeloma.  



Dr. Nadeem on the Emergence of Quadruplet Regimens in Multiple Myeloma 

Omar Nadeem, MD, a physician at Dana-Farber Cancer Institute and an instructor in medicine at Harvard Medical School, discusses individualizing therapy for patients with multiple myeloma.

As more therapies become available, more thought will have to be put into determining how best to sequence agents. In the relapsed setting, that will be the most important aspect of treatment, says Nadeem. If 4-drug regimens are adopted into the frontline setting, their impact on subsequent exposure to later lines of therapy and current standards of care, such as stem cell transplantation, will need to be assessed.

Escalation and de-escalation of therapy is another component of individualizing treatment. As such, tools are needed that will alert providers to when a patient who begins intensive therapy can de-escalate their treatment. These questions have never been truly asked before, says Nadeem. Over time, more medications and tools will be developed to individualize therapy for patients; this will be critical as no 2 patients with myeloma are alike, concludes Nadeem.

Dr. Nadeem on Individualizing Therapy in Multiple Myeloma

Omar Nadeem, MD, a physician at Dana-Farber Cancer Institute and an instructor in medicine at Harvard Medical School, discusses sequencing challenges in multiple myeloma.

Much of the decision comes down to toxicity, says Nadeem. As such, individual patient factors have to be taken into consideration when determining the next line of therapy. Additionally, the patient’s response to prior therapy should also be taken into account in order to gauge how much benefit they would derive from that class of agents in the subsequent setting.

Cytogenetic risk is also assessed to see if new high-risk mutations have been developed or acquired, adds Nadeem. Here, physicians are looking for the most effective and potent therapies to offset that risk. At this point, the data do not offer a clear directive on how to target specific mutations with available therapeutic classes.

However, venetoclax (Venclexta) does have very significant activity in patients with t(11;14) disease, says Nadeem, and if the safety concerns that have been noted with this medication become manageable, the targeted agent is likely to become available in the clinic for patients with that translocation.

Omar Nadeem, MD

Articles

Dr. Nadeem on the Integration of Isatuximab in Relapsed/Refractory Multiple Myeloma

Dr. Nadeem on the Emergence of Quadruplet Regimens in Multiple Myeloma

Dr. Nadeem on Individualizing Therapy in Multiple Myeloma

Dr. Nadeem on Sequencing Considerations in Multiple Myeloma