Transforming Care With Collaboration, Individualized Treatment, and Novel Therapies

Patients with chronic hematologic malignancies are living for decades, especially with new treatments, making it an important time to shape value-based treatments being offered to these patients, said Jennifer Vaughn, MD, during a fireside chat at the Cleveland Regional Institute of Value-Based Medicine (IVBM) event hosted by The American Journal of Managed Care.
Vaughn, a hematology specialist specializing in myelodysplastic syndromes at The Ohio State University, was joined by Akriti Jain, MD, a hematologist at Cleveland Clinic, to discuss quality care initiatives in rare hematological disorders.

With myelofibrosis, for example, the disease can be very high risk or very low risk, and there have been recently approved Janus kinase (JAK) inhibitors to treat the disease, with more coming. There are 4 approved JAK inhibitors1: ruxolitinib (Jakafi), fedratinib (Inrebic), pacritinib (Vonjo), and momelotinib (Ojjaara). With multiple treatments available, it’s important to understand the individual patient’s symptoms to choose the most effective therapy.

“One of the main things that we talk about these days is individualizing care, right? Not every patient is the same,” Jain said. “So, when I see a patient with myelofibrosis in clinic, the first question is: What are they presenting with?” If a patient has the typical symptoms of myeloproliferative neoplasms (MPNs), a JAK inhibitor is probably the right way to go, she said. If they don’t have those symptoms but they have anemia or thrombocytopenia, then a little more investigation is needed.

In the polycythemia vera space, there are also a number of agents
now available that can lead to a reduced risk of progression in the future. Vaughn explained that when she sees a younger patient, they now have
the opportunity to take aspirin and go to the doctor for routine phlebotomies and labs or a treatment that they can manage and can limit time away from work and their kids.

“That’s been, now, a really interesting discussion in that patient population for me, because there are many of my patients who have actually opted to go on therapy,” she said. “We all think of phlebotomy as this very low-risk, easy [procedure] to undergo, but phlebotomy is just a real…pain for them. They can’t spend the time away.”

She added that “time toxicity” is being considered more and more, which is a way to evaluate how much time patients spend having to engage in their health care treatments.

They went on to discuss updates in the National Comprehensive Cancer Network (NCCN) guidelines2 that are highlighting the combination of ruxolitinib with luspatercept or erythropoiesis-stimulating agents, because these other agents treat anemia, which is a known adverse event of ruxolitinib. Vaughn explained that if a patient has anemia or is borderline, ruxolitinib alone isn’t the best option in case it makes the anemia worse.
Clinicians who have a good experience with ruxolitinib in combination are comfortable using it, but the newest approval in the space, recommended as a category 2b in the NCCN guidelines, is momelotinib, which was approved for patients with myelofibrosis with anemia.3

Ultimately, the important thing is to make sure patients are living longer but also living better, Jain said, referencing a colleague, Aaron Gerds, MD, at Cleveland Clinic, who was supposed to be at the event speaking with them but couldn’t make it.

Considering the clinically meaningful end points in rare hematology, overall survival benefit is key, Jain said. It can take a long time to see that benefit though, which means patients are living longer, which is good. Another end point is event-free survival, and what the event is can change based on the type of cancer being treated. The top events are death and relapse or progression. In the case of MPNs, clots are an event as well. Lastly, events include going to a second line of treatment.

Increasingly, patient-reported outcomes (PROs) are being considered, which is the “living better” part of the equation. “PROs are a really important part of the secondary end points that we collect,” Jain said, and with new technology, collecting PROs is as easy as sending an email to the patient. The total symptom score is also a way to rate the patient’s overall quality of life, and that can be done in the clinic.

“I agree that the symptom score and patient-reported outcomes are becoming so essential, particularly in these diseases where people do live many years,” Vaughn said.

They also touched on the Inflation Reduction Act (IRA) of 2022, which is something Vaughn said she is very passionate about. Having spent some of her career in community practice, she had a lot of experience with patients who opted for less effective therapies because of the cost and the burden of high co-pays.

The IRA promises to cap out-of-pocket co-pays at $2000 starting in 2025 for Medicare Part D, and it will eventually move into Medicare Part B as well. The IRA smoothing process also helps to spread out co-pays over the course of the year.

“…Many of you have probably faced a patient who’s like, ‘Oh, I gotta pay for this now because I’m getting into my doughnut hole.’ I mean, my own father calls me and complains about this all the time,” Vaughn said.

She acknowledged the counterarguments to the IRA, that the drug negotiation aspect of it will reduce the incentive for innovation, but she finds it promising.

She did point out that $2000 a year is still a lot of money for people, even for a lifesaving therapy or one that can significantly improve quality of life.

“One of my mantras is to really encourage physicians to ask patients about whether or not they’re having any trouble with acquiring their drugs or [with] their co-pays,” Vaughn said. “It’s something I’ve incorporated into my practice, because I never have once had anyone be offended by that. All I say is, ‘Everything going OK? You’re getting your drugs on time? Any issues with the co-pay? Any concerns there?’ And that really does open up a great door to get patients talking to you, and then to start talking about…what they’re valuing in their care.”

The IVBM meeting also included 3 panel discussions. In the first panel of the night, Faiz Anwer, MD, of Cleveland Clinic; and Beth Faiman, DNP, PhD, of Cleveland Clinic, discussed best practices in multiple myeloma treatment, focusing on newly diagnosed and relapsed patients. Their conversation was moderated by Don Benson, MD, PhD, of The Ohio State University.

They emphasized the importance of clinical trials and collaborating across institutions to continue a patient’s treatment. Since bispecific antibodies can be given in the community setting, it’s important to know who to contact at the institution, Faiman said.

“Keeping those lines of communication open is super important, and we always send patients back [into the community],” she said. “We really don’t want to keep them [at the academic medical center]; they should be in the community by their house.”
In addition, they highlighted the importance of depth of response in multiple myeloma. With a deep remission, there is the possibility of dose de-escalation, and the data have shown patients who achieve minimal residual disease negativity could do well if they are taken off therapy. However, both Faiman and Anwer agreed that while multiple myeloma is highly treatable, it’s not curable yet, and patients aren’t ready to stop treatment entirely.

“We’re not clinically ready as a group [to stop therapy],” Anwer said. While the phase 2 MASTER trial (NCT03224507)4 showed it’s possible, it’s known that patients with high-risk disease relapse earlier and “there [remain] a lot of questions, which we still need a little longer data.”

The second panel brought together a group of pharmacists to discuss the evolving role of pharmacists in outpatient oncology care.

“We view pharmacy as really a role that is to serve our patients and to serve our faculty,” said Julie Kennerly-Shah, PharmD, MS, MHA, BCPS, of The Ohio State University Comprehensive Cancer Center. “We have clinical pharmacists in all of our hematology oncology clinics, and over the years [they] have, I think, enjoyed extremely positive relationships based on the care that the pharmacists provide and the clinical expertise that they share.”
She was joined by Corey McEwen, PharmD, MS, of Mass General; Patricia Roberts, PharmD, MS, BCPS, BCSCP, of University Hospitals; and Anthony Boyd, PharmD, BCPS, of Cleveland Clinic, who moderated the panel. They discussed the overall shift from inpatient to outpatient settings for cancer treatments and the evolving role of pharmacists in outpatient oncology care.

Referring back to the discussion in the previous panel, Roberts noted that
with chimeric antigen receptor T-cell therapy and bispecific antibodies, intensive monitoring is required and suggested, but the best value to patients
is being treated in the outpatient setting, which is preferred if it can be done safely and effectively.

The panelists also discussed the need for multidisciplinary approaches and the challenges of payer pressures and site-of-care mandates.

“I’ll be honest with you, I think site of care is a bit of a trigger word for us these days,” McEwen said. “All we really want to be able to do…is be able to decide ourselves where is the best place to treat these patients. And I think increasingly, we are seeing that decision is somewhat being taken out of our hands, and that’s a really big challenge for us.”

The final panel of the night brought together Alberto Montero, MD, of University Hospitals; Halle Moore, MD, of Cleveland Clinic; and Dionisia Quiroga, DO, PhD, of The Ohio State University Comprehensive Cancer Center, to discuss how to optimize care for breast cancer with a focus on integrating genomics. Ashley Davenport, MD, of The Ohio State University, moderated the discussion.

As more antibody-drug conjugates (ADCs) become available, determining the right sequencing of them is one challenge that was discussed. “As we think about value in biomarker testing, I can’t help but wonder, ‘Do we even need to be biomarker testing for this drug? Or do we need a better biomarker to help predict who’s going to respond so that we’re not treating patients who aren’t going to benefit?’ So, I think we have a lot of work to do in terms of figuring out who’s going to best respond” to the ADCs available, Moore said.

The challenges around drug toxicity was also brought up. Understanding and considering toxicity is important, Montero said, especially in the metastatic setting, where “patients are living longer, but philosophically, we know that we’re not curing them,” he said. He added, “We’re not going to cure anyone, but we want to treat them, but we also don’t want them to crash and burn after the first cycle and then abandon a potentially good drug.”

Quiroga noted that the ADCs are, unsurprisingly, outperforming most traditional chemotherapies, but the adverse effects may be tougher. She gave the example of a patient who might not want their children to see them lose their hair to avoid the conversation about cancer as long as possible, so the patient might not choose trastuzumab deruxtecan, despite the better progression-free survival.

“I think having good conversations with our patients is very important to convey what we see in the data, but also making sure that quality of life and what’s important is [prioritized for] them,” Quiroga said.

References
1. Sava J. Choosing the right JAK inhibitor for effective myelofibrosis treatment. Targeted Oncology. September 30, 2024. Accessed November 26, 2024. https://www.targetedonc.com/view/choosing-the-right-jak-inhibitor-for-effective-myelofibrosis-treatment
2. NCCN. Clinical Practice Guidelines in Oncology. Myeloproliferative neoplasms, version 2.2024. Accessed November 27, 2024. https://www.nccn.org/professionals/physician_gls/pdf/mpn.pdf
3. McNulty R. FDA approves momelotinib for myelofibrosis with anemia. The American Journal of Managed Care. September 15, 2023. Accessed November 27, 2024. https://www.ajmc.com/view/
fda-approves-momelotinib-for-myelofibrosis-with-anemia
4. Costa LJ, Chhabra S, Medvedova E, et al. Daratumumab, carfilzomib, lenalidomide, and dexamethasone with minimal residual disease response-adapted therapy in newly diagnosed multiple myeloma. J Clin Oncol. 2022;40(25):2901-2912. doi:10.1200/JCO.21.01935