In this journal section, we speak with cancer care practitioners about their clinical pathways and the pathways programs being used in their practice, how they are being applied in a particular disease state, and what challenges persist regarding treatment decision-making and personalized medicine.
In this “Pathways in Practice” installment, we spoke with Noopur Raje, MD, Professor, Medicine, Harvard Medical School; Director, Multiple Myeloma Program, Medical Oncology, Massachusetts General Hospital (MGH; Boston, MA) about the special challenges related to the use and maintenance of their clinical pathway for multiple myeloma. As a hematologist/oncologist at MGH, Dr Raje’s primary focus is in multiple myeloma and related research. Her laboratory focuses on bone biology and the development of novel therapeutics for multiple myeloma, as well as identifying and validating novel targets and translating them into clinical trials.
How are clinical pathways developed and used at your institution?
Dr Raje: We use clinical pathways more from a programmatic standpoint. With so many clinicians or caregivers—both nurse practitioners and physicians—and many affiliates within our cancer center, clinical pathways help optimize care delivery and treatments uniformly across the board and help maintain standards.
The pathways are evidence based and data driven, and largely maintained by our clinical group. Having the pathways is both a benefit as far as a point of reference to facilitate conversation and build consensus and also a benefit in the context of having the same best practices compiled together in one place for everyone. To be effective, pathways have to be easily available, and people have to be agreeable to following them. Pathways maintenance usually happens at the main site, MGH, and then we disseminate updates to our affiliates.
For dissemination and discussion, we have something similar to a tumor board every two months with our affiliates. We review pathways standards and treatments via a case based discussion to ensure we all agree on its guidance. Having a standard in place is a good idea because then the practice is more uniform—we want to avoid unnecessary variations in treatments when those variations deviate from evidence-based best practice. We aim to have optimized standardization in pathways—pathways that reflect the best and latest clinical evidence.
Within the pathways design, does guidance span across service lines? Do they include supportive care and palliative care for patients?
Dr Raje: For myeloma, it includes the bone targeted guidance. Palliative care is something we do think about. It has been less of a focus in the pathways, to be honest, but going forward I do think it needs to be incorporated. We have started incorporating, not just palliative care, but also lifestyle medicine into our standards. Those are newer things that we are highlighting right now but are not yet part of our pathways.
How does the pathway stratify patients with multiple myeloma to help guide treatment decision making?
Dr Raje: For myeloma, the first stratification is newly diagnosed vs relapse. In the newly diagnosed space, if we look at older adults, we stratify by frailty, age, and transplant eligibility. Once you have that, the next step is to determine what to do for induction. We have all agreed upon first considering a triplet induction.
We consider quadruplets also, but our favored pathway for quadruplets—as of right now until the data matures—is beyond a clinical trial. We have several clinical trials with quadruplets, both in the transplant eligible as well as the transplant ineligible patient population.
Within the newly diagnosed space, we also assess based on specific situations. We have preferences for people with renal failure or those with associated amyloid, for example. We have certain preferences in those patient populations for the upfront treatment.
The way we think about triplets is make sure you have an IMiD and a proteasome inhibitor in the mix. In certain situations, we may consider adding or substituting one of these classes with a CD38-directed monoclonal antibody. Preferentially, we would like to do it on a clinical trial, but if absolutely needed, we have used a quadruplet in a small proportion in the newly diagnosed.
In the relapse setting for myeloma, treatment is a little more challenging, largely because of the number of options available for patients. To put everybody in one bucket becomes really hard because it depends on the type of relapse, on the number of relapses, associated comorbidities and so on.
We have some ideas for early relapse vs late relapse and what patients have had before. Most of our patients are relapsing on lenalidomide maintenance. Depending on nature of relapse, we consider certain triplets that we prefer. Our focus is always to try and do clinical trials if possible, and if not, then do standard of care.
We have different triplet regimens, mostly pomalidomide containing regimens, and then we obviously cater to comorbidities—frailty, nature of relapse, renal function to the patient—and then we would pick one vs the other. We actually published our pathway in Journal of Oncologic Practice just last year.
Can you speak to some of the treatment challenges that exist in treating patients with multiple myeloma?
Dr Raje: The challenge is always that every patient is very different. To box everybody into a pathway sometimes becomes extremely challenging. The other challenge with myeloma, which is a good problem, is that we have so many treatment options. These options are all individually FDA approved though not necessarily FDA approved in specific combinations, but for certain patients we do need those combinations. There may be small studies looking at the combinations, like 30 patient studies, but that were never a registration study. It is safe to do the approved drugs, but there is no track record of them being combined together, so it is difficult when we get pushback from insurance for those reasons. Because MGH is a very large practice, we are able to fight that pushback. At the end of the day, it is really important that the patient gets the right treatment. Our care is very patient focused.
Because of our emphasis on unique patient needs, we do have a process to review exceptions. If your patient needs something that is not from the pathway, we have an off label committee that is a standing committee at the cancer center. If you have data to make a case, we get it through that committee. If somebody from my team needs to combine, for example, two drugs that are not registered in this combination and they have data to support it, we allow it. We have to have rules, but we also have to be able to have a system in place which enables us to deliver optimal care. Having this off label policy at our center allows us to do that. We use broader guidance like NCCN Guidelines to push back with insurance and get drugs covered for our patients.
How often is the pathway updated, and what level of evidence is required to determine whether the pathway needs to be updated? Who reviews or approves those updates?
Dr Raje: Whenever we have a new drug approval, we revisit our pathway. With myeloma, it is happening quite frequently—more than on a yearly basis—which, again is a good problem.
When we review new drugs, we have the joint purpose of assessing it for the pathway as well as getting the drug on formulary. When we are getting a drug on formulary, we have a very stringent methodology at the institution. We have to present data at the committee. Usually once it is an FDA approved drug, it is easy because most of those are approved based on phase III or very good phase II data. Nonetheless, we go through the whole review process to get it on formulary. When we do that, we also revisit our pathways to see where this new drug will be fitting in.
At the outset before it goes on to the formulary itself, we have to provide the institution certain metrics in terms of where we think we are going to use it and how much we are going to use.
It also helps that we have been a part of many of these trials—we are very active on the clinical trials front. We have already participated in these trials and have the experience, so we know what we want to put on formulary ahead of time. We also have the experience of having used these drugs before. We have much of the research elements in place already, so it is fairly easy for us to transition to the commercial use of these. Again, going through the committee allows us to incorporate it into the pathways pretty quickly.
What are the challenges to optimizing treatment decision making that you have seen in your practice?
Dr Raje: One challenge is that, by the time new drug combinations are approved, we are already way ahead. In the United States, we are a little more liberal with allowing their use. Getting official approval comes much later. As I mentioned, the pushback from insurance, the payment, is a hassle.
Another challenge is that we are starting to combine many of these drugs, and these are all individually very high cost drugs. Pathways is a good way to bring more value to treatment decisions and help reduce potentially avoidable resource use, but the pathways should also have the option like we talked about of providing individualized care where required.
End of the day, you have to create a pathway that allows you to achieve the best possible response and get the best possible outcome for your patient and keep that patient out of the hospital. In certain situations, you have to digress a little bit from that pathway. These cases are rare, but they do happen. We have been fairly successful because we have a very cohesive group of people, and we have put in place all of these processes like off label access to drugs and peer to peer review.
The biggest challenge in my mind is cost of drugs. We have a harder time from a reimbursement standpoint when combining two oral drugs, for example, two high cost oral drugs. We get pushback from insurance there. We do not get that much pushback when you have something that is given in the hospital vs oral because it is billed differently. I do think that is something that should change, and it should be more transparent. The future of treatments is not going to look that way, and these entities should be able to talk to each other.
