Peer Exchange: Current and Future Considerations in the Treatment of Relapsed/Refractory Multiple Myeloma

In a Pharmacy Times® Peer Exchange video series, experts discussed the current landscape and management of relapsed or refractory multiple myeloma (RRMM), including the latest data and potential treatment strategies on the horizon. The panel included moderator Bhavesh Shah, RPh, BCOP, Boston Medical Center; Douglas Braun, CSP, PharmD, RPh, American Oncology Network; Ryan Haumschild, PharmD, MS, MBA, Emory Healthcare; Robert Mancini, PharmD, BCOP, FHOPA, Saint Luke’s Cancer Institute; and Heather Pound, PharmD, BCPS, BCOP, Baptist MD Anderson Cancer Center.

The experts agreed that in this landscape, patients will still relapse, even with all the recent innovations in treatment. However, identifying these patients and establishing the criteria to do so is crucial.

Overview of Treatment Considerations

According to Shah, when he began practicing in 2003, only a minimal number of drugs existed for the treatment of RRMM, including vincristine, doxorubicin, and dexamethasone. At the time, patients would be admitted to the hospital for continuous infusion or a transplant.

In terms of how things have significantly changed since then, Mancini mentioned how his team deals with the trajectory of a patient’s disease and determining what symptoms are presenting that may show disease progression or relapse.

“I remember in 2015, when I gave the new drug update for HOPA [Hematology/Oncology Pharmacy Association], there were 4 new drugs in myeloma and all those things were just coming out. Every year we get more and more either expanded indications and/or new drugs and new mechanisms,” Mancini said. “So even without all of those things coming in, we still see issues with these patients relapsing. And I think that's what we expect to see in pretty much every myeloma patient that we’re going to talk about.”

Mancini further mentioned that International Myeloma Working Group criteria can be broken down into 2 categories: minimal residual disease (MRD) and standard response criteria.

In terms of clinical relapse, Pound added that her team follows patients’ urine proteins to see if they are becoming more symptomatic or having any more issues from the disease in the relapse setting.

“I think that 1 barrier to using MRD status, in the MRD or the relapse setting, would be putting patients through potentially unnecessary procedures with a bone marrow biopsy. Again, we know that MM is a heterogeneous disease and even within the bone marrow you can have patchy involvement with their disease status,” Pound said. “So I think it’ll be a little bit before we start to see MRD being assessed in the RR setting. But it’s definitely one of those things that we’re looking at up front.”

Treatment Strategies in Relapsed or Refractory Multiple Myeloma

In discussing what factors to consider when patients present in the RR setting and when deciding on a treatment, Pound said that looking at the original molecular and cytogenetic therapies, including their performance status and what therapy a patient has already received, is recommended. This can help the team decide on a more intensive chemotherapy with triplet or potentially quadruplet therapy.

“...Obviously 1 thing that we have to consider is what therapies they've received before. What have they received in the first-line setting? Were they
on maintenance [lenalidomide] after their transplant? Did they get a transplant? One of the things that I think will be really interesting as we move into the future, certainly with the GRIFFIN trial [NCT02874742] using quad therapies with [daratumumab] up front, is how does that change what options we have in the RR setting,” Pound said. “We always have to distinguish between the different classes of agents vs the lines of therapy. So again, as you mentioned, we have lots of different flavors of proteasome inhibitors and IMiDs [immunomodulatory imide drugs], monoclonal antibodies, and even some of our new BCMA [B-cell maturation antigen] therapies. Identifying [whether they are] refractory to a drug or...to a drug class, ...those things are really important [to] talk about.”

Haumschild added that looking at pathways is crucial, and the future of these therapies requires ensuring that health care providers are consistent in the manner in which they provide care.

“Especially when it comes to the disease state of MM, there are so many different therapies being introduced,” Haumschild said. “So are these MM pathways the silver bullet? Not exactly, but what we’re trying to do is establish at least treatment algorithms that we can generally follow so we can have better predictability in care, more consistent outcomes, more value-based decisions, and ultimately provide a really good patient experience. If we have patients come in, [we] look at the CRAB [hypercalcemia, renal failure, anemia, bone disease] criteria, cytogenetics, and then we really want to figure out, is a patient transplant eligible [or] not transplant eligible? A lot of times that [answer] can streamline the rest of therapy.”

As for the impact of coronavirus disease 2019 (COVID-19) on treatment and the changes it has brought about, Braun emphasized how the pandemic has affected everyone and patients’ access to care.

“We’re wondering [whether] we may not know the fallout for years to come if patients aren't getting diagnosed in a timely matter because they can't get to their doctor or they're doing telehealth visits instead of going in to get lab work. We just don't know. But, certainly...in our practice, we’ve seen a greater shift of driving toward oral therapy as opposed to IV therapy during COVID-19,” Braun said.

Targeting BCMA for Relapsed or Refractory Multiple Myeloma

Although BCMA is being introduced into the RRMM setting as the “new kid” on the radar, according to Shah––the first time there is an actual target in myeloma––many providers are anti-BCMA. Haumschild went into more detail about the excitement over this target therapy compared with previous therapies. “When you think about the past, you think about how many lines of therapy we had to switch, and we came to fourth- and fifth-line therapies [and] really struggled with what to put patients on, and do we just enroll them on a clinical trial. And I think that’s why the BCMA target therapy is so exciting for us because it’s really meeting a patient need that we otherwise didn’t have,” Haumschild said. “And I know that’s something we were excited about when it came to launch. We wanted to be ready to operationalize it. The medication does come with some considerations: it was FDA approved with a REMS [Risk Evaluation and Mitigation Strategy] program.”

However, as with other therapies, there are some roadblocks that need to be brought to attention, according to Haumschild.

“One of the things I just want to bring up is that... I’ve actually had a lot of people across the country reach out to figure out how to operationalize this. And we’re very collaborative, you know. Oncology pharmacy is a small world, and we’re always here to help each other and especially with something like belantamab, which is kind of new and innovative,” Haumschild said. “One of the key pieces that I just want to share is we’re so used to managing REMS sometimes in the MM clinical [setting] only, right? So we keep [lenalidomide] in the clinic. Not a lot of specialty pharmacies have access to the IMiDs, so we’re used to just sending it outside.”

Looking Ahead

As for what the experts are looking forward to in RRMM therapy, Pound mentioned bispecific antibodies as being of great consequence for her practice.

“From more of a community practice [viewpoint], I think that the bispecific antibodies...are going to be kind of game changers for us. Some of those are in early phase 1 or phase 2 trials. I think when people hear bispecific or ‘bis’ they kind of cringe a little bit. I know that I do every time the [blinatumomab] is mentioned,” Pound said. “So certainly, one of the things that I’m excited about is that there are some bi therapies...out there that target BCMA and they are available as a bolus infusion once a week. Obviously, there are some that are still a continuous infusion, but I think from an operational perspective...the bis [have] some exciting data....”

For Haumschild, the BCMA therapy and its different combinations are what he is looking forward to.

“I think there’s probably 3 studies I’m interested in the most. Most were actually presented at ASH [American Society of Hematology meeting], so I’m interested to see what the data are going to be like. The study looked at BCMA-targeted therapy, [belantamab mafodotin] with pomalidomide and dexamethasone. And knowing that it’s phase 1, we’re still trying to evaluate what that maximum tolerated dose is,” Haumschild said. “But it’s really for patients that have had greater than 2 lines of prior treatment, have a prior exposure to lenalidomide and a proteasome inhibitor, and were refractory to their last line of therapy. And I think that’s something that is going to be interesting for us.”

When asked about advice for pharmacists, Pound suggested not underestimating the power of supportive care as a clinical pharmacist.

“Certainly, as we’ve talked about, [with] all of these different therapies and exciting things that we have, we still need to make sure that [patients are] reaching appropriate antimicrobial therapy. With the renal dysfunction, do we need to adjust any of their myeloma therapy or any of the other medications that they might be on? Those are...always the things that are kind of in the back of my mind with myeloma patients as well,” he said.

For Mancini, having the resources and knowing what they are and how to use them is crucial for such a complex therapy.

“In the end, understanding the quirks of these medications, how to manage them, and how to support these patients is really important for the success of the treatment as well as for...our own well-being,” he said, “so we have dreams rather than nightmares.”

REFERENCE

Current and future considerations in the treatment of relapsed/refractory multiple myeloma. Pharmacy Times®. Accessed March 18, 2021. https://www.pharmacytimes.com/ peer-exchange/current-and-future-considerations-in-the-treatment-of-relapsedrefractory-multiple-myeloma