Nuanced Decision-Making Strategies Are Needed as the Multiple Myeloma Paradigm Grows

Saad Z. Usmani, MD, MBA, FACP

Treatment selection for patients with multiple myeloma is becoming increasingly complex given the introduction of quadruplet therapies, immunotherapeutic strategies, and novel small molecule inhibitors, said Saad Z. Usmani, MD, MBA, FACP, who added that individualizing therapy and communicating with colleagues about emerging data are of the utmost importance to ensure optimal patient care.

“A lot of progress is being made in multiple myeloma at a very fast pace,” said Usmani in an interview with OncLive^® during an Institutional Perspectives in Cancer (IPC) webinar on multiple myeloma.

“It’s always difficult to keep up with the data and make sense of them. That is why having these engagements where you can talk about these data with colleagues is important. Hearing the data in the context of everything that is ongoing in the field is even more important for our clinicians in the academic setting, as well as the community. It helps us in taking care of our patients better knowing what kind of trial options are out there for them. If our patients need them, we can refer them to our academic colleagues.”

During the interview, Usmani, chair of the IPC event and a hematologic oncologist and chief of the Myeloma Service at Memorial Sloan Kettering Cancer Center (MSKCC), shared key takeaways from presentations given during the meeting on the evolving paradigms of frontline, early relapsed, and late relapsed multiple myeloma, the current role of bispecific antibodies and CAR T-cell therapy, and emerging immunotherapies and also trials in progress in the space.

OncLive^®: During the IPC meeting, Neha S. Korde, MD, of MSKCC, spoke about frontline treatment in multiple myeloma, including quadruplet regimens and minimal residual disease (MRD)–adapted approaches. What should be underscored regarding the management of newly diagnosed disease?

Usmani:In Dr Korde’s presentation, she summarized some of the newly diagnosed [multiple myeloma] data, specifically [regarding] the use of quadruplets in the frontline setting for transplant-eligible and some transplant-ineligible patients. She also highlighted some emerging data in high-risk patients, specifically in the context of what we are trying to achieve during that first year of diagnosis.

We are trying to get patients into the best depth of response, and then, the idea would be to sustain that kind of response. These are some of the initial building blocks as we build the new scheme of treatment where we can define the duration of treatment for patients with multiple myeloma. If someone achieves sustained MRD negativity for a certain period, will it be OK to stop therapies [in] clinical trials?

Urvi A. Shah, MD, of MSKCC, spoke to some of the factors that inform treatment selection for patients with early relapsed multiple myeloma. What are some of these features?

Dr Shah covered management of early relapsed multiple myeloma. She added some of the updated information about the randomized phase 3 studies in that space. It is a very busy space from a therapeutic choice perspective. She went through each of the clinical trials and what kind of patients those clinical trials would be applicable for. [She also] highlighted that we have to pay attention to prior therapies, patient preferences, patient-related factors, and how quickly the patient’s disease is relapsing, and put all of that together in picking the right treatment strategies for our patients.

Next, Malin Hultcrantz, MD, PhD, of MSKCC, described agents for consideration in patients with late-relapsed multiple myeloma. What are some of these considerations?

In the late relapsed space, novel therapies are emerging with cereblon E3 ligase modulating drugs, as well as exportin-1–based combinations with selinexor [Xpovio]. [Those] data were covered by Dr Hultcrantz in her presentation. She also covered the emerging data with venetoclax [Venclexta] combinations in the late relapsed setting for [patients with] translocation 11;14 and BCL2 overexpression.

It is not just about some of the immunotherapeutic strategy advances, but there are several small molecule and oral immunomodulatory therapies emerging in multiple myeloma, which are complementary to the immunotherapeutic advances.

Sham Mailankody, MBBS, of MSKCC, spoke about the current state of bispecific antibodies and CAR T-cell therapies in multiple myeloma. How are research efforts trying to expand upon what is known about these therapeutic modalities?

The bispecific [antibody] and CAR T-cell therapy space is very busy, and I suspect it is going to get busier. We have a lot of data with different BCMA-directed therapies, but also emerging data with GPRC5D- and FcRH5-directed therapies and not just in the bispecific antibodies space.

My colleague Dr Mailankody presented the first GPRC5D[-directed] CAR T-cell therapy data and updated [us regarding] the Allogene off-the-shelf allogeneic CAR T-cell therapy data with BCMA. There are strategies being developed on how we can use CAR T-cell therapies, bispecific antibodies, or trispecific antibodies in going after more than 1 target. I suspect that will become a very busy topic for future conferences and CME [continuing medical education] programs. There are going to be a lot more data at the 2022 ASH Annual Meeting and Exposition, so I am excited about this specific area.

Finally, Alexander M. Lesokhin, MD, of MSKCC, discussed emerging immunotherapies and trials in progress in multiple myeloma. What research are you keeping an eye on that could have clinical implications for patients?

The talk by my colleague Dr Lesokhin that covered emerging immunotherapies in multiple myeloma and other strategies in the space highlighted how far we’ve come and the direction we are headed. It included new vaccination treatment strategies that are being explored in clinical trials in the context of post-transplant maintenance treatment, as well as in the relapsed/refractory space. These are not new concepts. It is just that we have better partner therapies in the spectrum of myeloma settings. That was something he highlighted.

He also talked about some of the novel checkpoint inhibition strategies and the anti–CD47 strategies that are being explored in myeloma. The latter strategies are again, not new ideas and are being explored in other hematologic malignancies. [We have] a lot to look forward to in the coming years.