Drug Sequence Might Not Significantly Impact Survival Outcomes of Patients with Lymphoma

Mark Sorial, PharmD, BCOP, RPh, a hematology and oncology clinical pharmacist at Massachusetts General Hospital in Boston, Massachusetts, discusses drug sequencing and the importance of standards of care (SOC) in clinical practice with Pharmacy Times at the 65^th American Society of Hematology (ASH) Annual Meeting & Exposition, taking place December 9-12, 2023, in San Diego, California. Sorial highlights “practice-changing” results from the study, the pharmacist’s role in a collaborative care team, especially when there is no SOC for the disease, and prospective research that will look at adverse events related to drug sequencing.

PT Staff: What is the importance of universal SOC for different disease states?

Mark Sorial, PharmD, BCOP, RPh: So universal SOCs or guideline-based recommendations are fairly important. They help standardize practice and they help make sure the drug gets the best benefit at the best time. So I feel like it's extremely important when we have diseases with lots of different subtypes, a different risk stratification, or if you have a disease where there's a lot of options- how do you pick? Having that extra consensus or that SOC to help drive first line therapy [and] second line therapy just makes it that much easier to deliver the benefit to the patients.

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PT Staff: How do diseases without a SOC impact the pharmacists’ role in treating patients?

Mark Sorial, PharmD, BCOP, RPh: In the pharmacist’s role, when we have a disease state where we have a really good SOC or guideline recommendation for first-, second- or third line, it makes our role much easier. So at our institution, Massachusetts General Hospital (MGH), we as a pharmacist are heavily integrated in the clinic. And we're oftentimes talking to the patient upfront before they start therapy— doing a chemotherapy teach, making sure that supportive care needs are there, and assisting with anything that may be a barrier before starting therapy.

So all of that is already known. we've vetted the challenges and we know what to do [so] it's not a surprise. In areas where there isn't a SOC, there's a lot of overlap between the pharmacist’s role and the physician’s role, and it becomes a lot more collaborative at that point. So I'm really lucky at MGH; we’re integrated into a hugely collaborative group that's collaborative with the physicians, the advanced practice providers, and of course the pharmacists, [along with] the nurses. Oftentimes, in situations where there isn't a SOC, it becomes a huge collaborative discussion and then it ends up being a shared decision-making event with the patient.

PT Staff: Can you outline the recent global retrospective cohort study looking at therapy sequence on patient survival, and findings related to study outcomes?

Mark Sorial, PharmD, BCOP, RPh: So in T-cell lymphoma, we have a handful of agents that are used for T-cell lymphoma; then again, most of them are based on small studies or single arm studies. So we don't really have a lot of information on what to use first or what to prioritize. And the unfortunate news is people with T-cell lymphoma often relapse. So these patients tend to get most of these drug classes anyway, the only difference between them being that the sequence of therapies are different for each patient.

We aimed to look at the potential benefit, or lack of benefit, [of] using the treatments in a certain sequence, using what was used in the global retrospective dataset. And this was data from 15 academic sites across the world, comprising 6 continents. So this was a massive effort with investigators all over the world.

So we looked at the different sequences. The main groups would be patients who got epigenetic therapy (second line), patients who got chemotherapy (second line), or patients who got signaling inhibitors like small molecule inhibitors (second line). So the first thing we looked at is survival difference based on these therapies, second line. And then the next thing we looked at is survival different based on what you received second line, and then what you go to on third line. So [we asked] “Does the sequence between second- and third-line matter?”

What we ended up finding is there's not too much of a difference in the sequence. There is a survival benefit with signaling inhibitors, specifically angioimmunoblastic T-cell lymphoma (AITL) patients. But the sequence overall, going from second to third line, doesn't really play a part, the survival benefit is just using signaling inhibitors in second line.

This is potentially practice changing. I think 1 thing is you don't have to worry about, “What am I going to give them now? What am I going to save for later?” I think 1 of the limitations to our study is that when you're looking at sequential decision making, potentially every line of therapy, every decision changes the risk of having a treatment potentially.

Our next steps that I can talk about is [that] we're teaming up with machine learning experts at Massachusetts Institute of Technology and Harvard School of Public Health. Yeah, and we're applying really cool machine learning methods, 1 of them called dynamic treatment regimes. which basically adds a weight to what line of therapy you are, where you got your therapy, etc. So hopefully, that will come out in the next 6 months or so.

PT Staff: Does therapy sequence influence severity or presence of adverse outcomes (AEs)?

Mark Sorial, PharmD, BCOP, RPh: We have some really exciting work happening now to answer some of those questions. With this retrospective data set, we don't have access to toxicity data. So one of the one of the limitations is we're not able to know which one is more toxic at what time there are limitations with collecting toxicity data retrospectively. So a lot of it is not reported uniformly across sites. Some toxicities are subjective and need to be patient reported, which not everyone does the same way. So with our retrospective dataset, we're not able to answer that. But we see in most other indications, also the cancers, that some toxicity can be cumulative. So for example, myelosuppression, or cytopenia. You see people who have gone through more lines of therapy end up having more difficult time recovering from a bone marrow toxin like chemotherapy. So right now, our study and our findings thus far support the use of the therapy that would be best fit for the patient at a given time, and a given access at any country. So this was a global study that we can support, even though every drug is not approved or available in every country. It doesn't really matter, based on what we're finding. So far, at least.

PT Staff:How could pharmacist involvement impact sequence decision-making and AE management? How might they be impacted by it?

Mark Sorial, PharmD, BCOP, RPh: Even when there is a SOC in line, there is, of course, a lot of consideration going into the potential toxicities and the patient's specific comorbidities. So if someone has a certain comorbidity or or medical history that may predispose them to more toxicity, and we would be mindful of that, and that's in in situations where we have a clear pathway of treatment, but also more so in situations where we don't have a clear decision on what to use first. In my experience, and my role at Mass General, like I said, we're really collaborative. So in these situations where we don't have a first line therapy, we don't really know what's more effective than this or that these decisions are very dynamic. You know, they involve, of course, nursing, they, of course, involve the physician, the pharmacist, and some of the lines of what each person's role is and the team kind of get blurred.

So there are times where the physician will put on a pharmacist hat on and say, "Well, I'm worried about drug interactions." And there are times where I'm potentially grading their toxicity using the CTCAE, which is classically a physician assessment, so at these levels, where there's no SOC and these rare disease seats, I feel like the pharmacist, who is already integral into the team, becomes much more dynamic player, as well as nursing and mid level practitioners.