AJMC®tv Interviews, January 2018

Dr Stephen Schuster Outlines CAR T Results Seen in Leukemia, Lymphoma, and Myeloma

Stephen Schuster, MD, of the Perelman School of Medicine at the University of Pennsylvania provides a summary of results seen with chimeric antigen receptor (CAR) T-cell treatments in leukemia, lymphoma, and myeloma.

What have been the promising results seen in CAR T-cell treatments for patients with leukemia, lymphoma, and myeloma?

There are lots of promising results in leukemia and lymphoma. The myeloma results are early, but the leukemia and lymphoma results have already translated into 2 commercially available products. The leukemia, specifically, is B-cell acute lymphoblastic leukemia [ALL], [which is] the leukemia that is most common in children. The target of therapy is CD19, so this is CARs directed against CD19, which is on the surface of B-cell ALL. And there, there’s an 80% response rate, and at 1 year, 75% of the kids are in good shape, in remission. And these are kids with ALL, who have disease that is either recurred after standard therapy or doesn’t respond to standard therapy or [who] have had transplants and have recurrence after transplants. So, it offers a potentially long-term, durable remission for these kids.

The lymphoma indication, so far, is diffuse large B-cell lymphoma, and there we have roughly 40% remission rates, regardless of which study you’re talking about and which CAR T cell you’re talking about—and they’re durable. So, I have some of the longest follow-up, which I published [December 10, 2017] in the New England Journal of Medicine, and these patients in remission, it lasts for years. The median follow-up in that report was 29 months, and none of the respondents had relapsed. So, this is a breakthrough for relapsed/refractory lymphoma patients who don’t respond to conventional therapies or to salvage therapies.

With regard to myeloma, they’re at about where lymphoma was 3 years ago. They need more trials with larger numbers of patients and longer follow-up, but preliminarily, the target, [B-cell maturation antigen] on the malignant plasma cells of myeloma, looks very susceptible to the CAR T approach. Lots of things about CAR T at this meeting; it’s clear to me that CAR T cells are a paradigm and we can make CAR T cells to any specific tumor antigens or viral antigens, for that matter, and have a T-cell therapeutic approach.

Dr Julie Wolfson Highlights Different Outcomes in AYAs With ALL Compared With Children

Adolescents and young adults (AYAs) with acute lymphoblastic leukemia (ALL) tend to have worse outcomes than children with ALL. New research published at the 59th American Society of Hematology Annual Meeting and Exposition delved into the reasons why, explained Julie A. Wolfson, MD, of the University of Alabama at Birmingham School of Medicine.

How do outcomes of AYAs with ALL differ from children?

Adolescents and young adults, or AYAs, the National Cancer Institute defines as patients who are diagnosed with cancer between the ages of 15 and 39. AYAs with ALL, in specific, have poor survival compared with children. So, children, in our study, we had comparable survival to what’s been shown nationally before, which is about 70% to 80% depending on their age; in AYAs, it’s more 35% to 45%, depending on the age, as well.

What are the reasons for the differences in outcomes between AYAs and Children?

So that’s a really important question, and it’s something that we’re really all trying to get to the bottom of. In our study, what we looked at was, in specific, in AYAs what predicted that poor survival. And there were 2 different times when they relapsed, and in terms of the risk of that relapse, we found that if they were going to relapse on therapy, there was about a 2.2-fold increased risk in patients on therapy if they were from nonwhite races or ethnicities. And there was a 2.6-fold increased risk of relapse if they were not enrolled on a clinical trial compared with patients that were enrolled on a clinical trial.

But then when we looked at the risk of relapse after they nished treatment, it was actually the duration of therapy. So, for each additional month of maintenance treatment that they had, there was a 30% decreased risk of relapse, and for each additional month of consolidation treatment, there was a 20% decreased risk of relapse. There was also a trend toward association with socioeconomic status and insurance there.

Dr Joshua Richter Discusses the Patient Financial Burden of New Treatments and Cures

This is a critical time for the healthcare industry to evaluate how patients are financially burdened by novel treatments that promise tremendous outcomes, said Joshua R. Richter, MD, of the John Theurer Cancer Center.

As new, more expensive treatments improve survival, how can clinicians identify and address the burden of financial toxicity?

I think this is something that’s really critical and is becoming more and more of an issue: that we can no longer, as physicians, bury our heads in the sand. [We] need to understand where the difficulty comes in with this. We have a lot of new drugs, and these drugs may offer many of our patients tremendous outcomes. But there is also a significant amount of financial burden that does come across, not only to the patient, but to their family. And while some of this is simply perceived by the patient, some of this can be quite real and patients often plunge themselves into deep financial trouble in order to support the care for their own disease, and this may affect the family, as well.

So, this is really kind of a critical time for us to evaluate things on a global standpoint. Yes, we need to be concerned about the system as a whole, but we need to get more granular and focus on what are the deleterious effects that we’re seeing on a patient-by-patient level in terms of the financial burden that we’re seeing with these great new therapies.

Dr Thomas LeBlanc: Patients With Blood Cancers Less Likely to Use Hospice Care

Patients with blood cancers tend to use hospice care services less frequently overall than patients with solid tumors. Although there has been an increase in hospice care use among patients with blood cancers, there has been a failure to increase hospice use meaningfully, according to Thomas LeBlanc, MD, of the Duke Cancer Institute.

How does hospice use differ between patients with blood cancer and patients with solid tumors?

We know from multiple papers and the literature that patients with blood cancers tend to use hospice care services less frequently overall than patients with solid organ tumors. This is something that’s been shown repeatedly over time and something that we don’t entirely understand, but we do have some ideas about in terms of what might be driving this difference. The research that we presented at this year’s ASH Annual Meeting included some evidence that hospice use probably is increasing, actually, in hematology. We looked specifically at Medicare beneficiaries in the SEER [Surveillance, Epidemiology and End Results] data set who have leukemias of various types, so both acute leukemia and chronic leukemia. We saw a significant increase in hospice use between 2001 and 2011, from about 35% in 2001 up to almost 50% in 2011.

Another study presented at this year’s ASH Annual Meeting showed a similar increase in patients with multiple myeloma. However, what we’re also seeing is a failure to increase hospice use meaningfully, and what I mean by that is, patients with hematologic malignancies, when they do use hospice, which again is less frequently than those with solid tumors, tend to use it for a lot shorter period of time. We found an average hospice length of stay of only about 9 days among hematological malignancy patients with leukemias.

More concerning, though, we found that those who are dependent on transfusions before hospice referral only used hospice for about 6 days. Those who do hospice care will tell you that using hospice care for just a few hours or a few days, or even maybe a week or two, is really not enough to derive the maximal benefits for patients and families when we know that it is really high-quality care for those who are at the end of life who need that care, in terms of improving how they feel and their ability to stay at home when their time is short.

Dr Nina Shah on the Benefits of Outpatient HSCT When Possible

Providing outpatient hematopoietic stem cell transplant (HSCT) when patients are eligible is a good way to reduce costs without impacting outcomes, explained Nina Shah, MD, associate professor, University of California, San Francisco School of Medicine.

Would it be more cost-efficient to conduct outpatient HSCT if outcomes are comparable and proven safe compared with inpatient transplant?

We just published a paper on this, this year from a large group of patients. And what we know is, for patients who are eligible—and

this is often a decision that’s between the physician and the patient—patients who are eligible for an outpatient transplant, they do great. They do just as well. And there is less cost to the entire medical system.

I think that if we’re going to use that approach, we have to get insurance companies to get on board to help patients pay for things like, for example, hotel rooms near the transplant center or helping a caregiver with their off time from work. And that will actually be more cost-efficient than having the patient in the hospital for 16, 18, 20 days. And patients actually feel more free, that they can do things a little more freely without being tied to a hospital bed. So, I’d really like to see us work together with the payers.

Dr Derek Raghavan Outlines Challenges to Implementing Evidence-Based Guidelines

Physician belief in the art of medicine is running up against the challenge of costs being shifted to patients and health systems and the desire of payers to have less variation in care, said Derek Raghavan, MD, PhD, FACP, FRACP, president, Carolinas HealthCare System’s Levine Cancer Institute.

What are the culture challenges that make it difficult for health systems and practices to implement evidence-based guidelines?

It’s becoming increasingly challenging to structure our approach to medicine, and there are a whole bunch of issues that get in the way. I think the first, and most important one, is the territorial imperative of the physician. Most physicians like to be independent. They believe in the art of medicine. They feel there is a nuance that will be available with their own personal skill. And, to be truthful, there is something to be said for that. The art of medicine is important. The more experienced physician is going to be, probably, better than the less experienced physician. Part of the difficulty is that some of the art of medicine is predicated on opinion rather than fact.

The second issue that is very challenging at the moment is the fact that we can no longer provide the medical care that we have traditionally with the money that’s available to support it. Costs are being shifted to patients; costs are being shifted to healthcare systems. So, there’s a tension that is driven by that. The people who pay for healthcare, whether it’s governments or health insurance funds, are looking for less variation and more structure and a bigger evidence base.

There has been a symposium at the American Society of Hematology meeting focused on the use of guidelines and how to disperse those guidelines into clinical practice, thinking about the impediments to the use of guidelines by physicians.

Dr Kerry Rogers: Ibrutinib's Impact on Vaccine Response

Ibrutinib has the potential to improve vaccine response for patients with chronic lymphocytic leukemia, and an ongoing trial will help provide a better understanding, explained Kerry Rogers, MD, assistant professor, internal medicine, Division of Hematology, The Ohio State University Comprehensive Cancer Center.

How does vaccination influence the response of patients with chronic lymphocytic leukemia to ibrutinib?

Ibrutinib is an immune-modulatory agent, so it has the potential to improve vaccine responses. However, we don’t have enough data [that are] looking at this yet to have a firm conclusion as to how ibrutinib affects this. We have an ongoing study that looks at vaccinating people and then treating them with ibrutinib or treating them with ibrutinib and treating them with vaccines that will answer the question as to whether or not ibrutinib can boost vaccine responses. We suspect, based on its immunologic actions, that it might, but that is something that we’ll have to see.

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