May 15, 2019
ASCO Daily News Editor-in-Chief, Dr. John Sweetenham on Hematologic Poster Presentations To See at #ASCO19
Welcome to the ASCO Daily News podcast. I'm Lauren Davis. And joining me today is Dr. John Sweetenham, the ASCO Daily News editor-in-chief. As attendees are getting ready for the annual meeting, Dr. Sweetenham will highlight some of the poster sessions and hematologic malignancies that will capture the attention of attendees. Dr. Sweetenham, welcome to the podcast.
Thank you. It's good to have the opportunity to talk.
We're glad you're here. For attendees who are interested in
hematologic malignancies, what areas in this specialty are you most
looking forward to?
So I think at ASCO this year in heme malignancies, I would
characterize a lot of the studies that are being presented in
poster format as confirmatory, or long-term confirmation of some
earlier results. But I think they're no less interesting because of
that. And I think that there is some important follow-up data,
particularly in CLL, and some important confirmatory data for CAR
T-cell therapy and hematologic malignancies.
Added to which, I think there are a lot of potentially exciting new
agents for the treatment of acute myeloid leukemia, in particular.
That's been an area of a lot of interest and a lot of new treatment
developments over the last two to three years. And I think that the
poster sessions at ASCO this year confirm that trend is still
ongoing and that the outlook for this very challenging group of
patients is improving.
That's great. What else can attendees expect this year? Any
surprising or practice-changing data?
I think, in terms of practice-changing data, I would list some of
the specific abstracts which I think, as I mentioned earlier, are
really confirming the importance of some agents and certainly will
confirm practice changes that have happened over the last couple of
years. To give you a couple of examples of that, perhaps I'll start
with chronic lymphocytic leukemia. The RESONATE study was a very
important study for patients with relapsed and refractory CLL,
which assessed the use of ibrutinib, a once-daily Bruton's tyrosine
kinase inhibitor against ofatumumab in this group of patients.
The original study was published in The New England Journal, but at
the meeting this year, there is mature follow up, a now six-year
follow up of patients treated on this study. And the encouraging
news is that the initial ibrutinib treatment, which was originally
shown to produce improved overall survival, that has been
confirmed. So the median duration of ibrutinib treatment on this
study is now 41 months. So it really is quite extensive follow up
at this point.
And encouragingly, the overall survival and median progression-free
survival benefits, which was 44.1 months for the ibrutinib arm
versus 8.0 months for the ofatumumab arm, that has been maintained.
And so it's clear that the long-term therapy with ibrutinib remains
highly effective and that the number of patients who are required
to discontinue ibrutinib because of adverse events is fortunately
relatively low.
So I think it confirms ibrutinib now across just about the entire
spectrum for CLL as the important treatment, both in front line for
those patients who are previously untreated, and in second and
subsequent-line therapy for those who've had some other agents as
the first-line treatment. I think that is very important.
And along with that, there is a cautionary note from a study which
explored the second cancer incidence in CLL patients receiving BTK
inhibitors. Contextually, there's been quite a lot of data, over
the years, exploring second malignancies in patients with CLL. In
this particular study, they did actually suggest that there
probably is a somewhat higher incidence of second primary neoplasms
in patients who are taking ibrutinib for CLL.
And those included cancers at the lung, melanoma, prostate, and
bladder cancer. So I think, at this point, this is just an alert
and something that we will need to watch closely as it does appear
as if there is a slightly elevated risk of second cancers in these
patients.
And then one other follow-up study, which I think is of importance,
is the fact that second-generation BTK inhibitors are now really
starting to gain some traction in CLL. And there was a nice study
presented in poster format which is going to explore the use of
acalabrutinib, which is a second-generation BTK inhibitor, in
patients who were intolerant of ibrutinib.
So for those patients who need to discontinue ibrutinib because of
adverse events, the second-generation acalabrutinib is effective
with an overall response rate of 77% and well-tolerated so that if
patients are in tolerance of ibrutinib, they certainly do have
other options.
I think, also, to complete the CLL field, there is a great deal of
interest in the potential use of CAR T-cell therapies for CLL. And
although it is very immature and the data to be presented at ASCO
poster are very limited, it is just worth pointing out that there
is an ongoing ZUMA-8 study for patients with relapsed and
refractory CLL exploring the use of CAR T-cells. And I think that's
going to be important. It will be very interesting to watch how
that develops over the coming year or two.
Another area which I think is very important is that we're starting
to see now that there are some studies which are really exploring
not only the disease-related benefits of some of these therapies,
but are also starting to look at patient-reported outcomes. And
there are two posters, in particular, which I think are interesting
in this regard. There is one study which looked at patient-reported
outcomes in patients with Waldenstrom's macroglobulinemia who were
treated with ibrutinib as a single agent or in combination with
rituximab.
So in the iNNOVATE study, it was demonstrated that ibrutinib plus
rituximab produced higher sustained hemoglobin improvements and
meaningful improvements in other laboratory parameters when
compared with placebo and rituximab. In this study, the
investigators have gone a step further and have actually looked at
patient-reported outcomes and shown that, in addition to the
standard response improvements that are seen, there's a clear
improvement in patient-reported outcomes associated with the use of
this novel combination with ibrutinib and rituximab.
And so along with the improvements in anemia, for example, there
are marked improvements in fatigue-related symptoms, constitutional
symptoms. And the clinical improvements are truly meaningful. And
that's actually mirrored in a different context, but in patients
with multiple myeloma who were previously undiagnosed and treated
with a novel combination of daratumumab, lenalidomide, and
dexamethasone versus the same regimen but without the
daratumumab.
And here, again, there is important patient-reported outcomes
demonstrating that, essentially, with the novel combination,
patients feel better more quickly. So the clinical responses that
have been demonstrated on that trial are confirmed by
patient-reported outcomes, which demonstrate that patients are
truly feeling better. So, again, I think at the patient level,
these are very important data.
Some other things that I think are important to look out for at
this year's meeting, there are a series of posters which explore
novel therapies for acute myeloid leukemia and myelodysplastic
syndrome. Without listing these in great detail because there are
several of them, I would simply say that these studies add to the
extraordinary expansion of available treatment options for patients
with AML that we've seen developing over the last few years.
And I think that the treatment landscape for these patients is
really changing now. Sequencing prior to therapy is becoming
important as more novel targets are identified, but consistent with
the trend we've seen in the last two or three years, more important
emerging therapies for patients with acute myeloid leukemia.
Shifting gears for just one moment and looking at patients with
B-cell lymphoma, and specifically aggressive non-Hodgkin lymphomas,
I think that there are a couple of studies here which show promise,
although certainly I wouldn't categorize them right now as being
practice changing, but the findings are interesting. One of those
is, again, in the context of CAR T-cell therapy.
So it's difficult to talk about heme malignancies at the moment and
not talk about CAR T-cells because there's such a lot of buzz and
excitement around those. And one of the areas where this
intervention is now FDA approved is in the treatment of patients
with relapsed, aggressive non-Hodgkin lymphoma, particularly
diffuse large B-cell lymphoma. And that was the subject of the
so-called ZUMA-1 study, which was a phase 1/2 study of axicabtagene
ciloleucel in patients with refractory large B-cell lymphoma.
The study reported out some months ago now, but one of the concerns
that some of us have had is that this may be a very reasonable
treatment for the young patients with a good performance status who
typically don't represent the bulk of patients with large B-cell
lymphoma. But what about those patients who are older? And how do
they tolerate this therapy? And what's the outcome?
And in a study that's going to be reported at ASCO this year, the
investigators of the ZUMA-1 study conducted a specific subset
analysis on that group of patients who were aged 65 years or older.
It's a small group. But I think the take-home message from the
study is that the outcomes in this group, in terms of the overall
response, complete response, and overall survival rates are very
comparable to the younger age group. And the toxicities are very
comparable to the younger age group, as well.
So I think this is important that age, in itself, may not be a
barrier to the applicability of CAR T-cell therapy. And that's a
very important message. The flip side of that is that these one, it
seems a pretty highly selected group of patients aged 65 years or
older. And certainly, that's reflected in the performance status
and the IPI scores of these patients as reported in the
abstract.
So they may be a highly selected group of patients aged 65 or over
with this disease, but nevertheless, I think they're quite
compelling results. And I think it speaks to the broader
applicability of this therapy in patients with relapsed, aggressive
lymphoma. The big remaining question being, how are patients and
perhaps, more importantly, how is the health system, as a whole,
going to cope with the cost and the financial toxicity associated
with this very important new treatment?
Again, on the subject of aggressive B-cell lymphoma, there is one
more study which caught my eye. And it's interesting for a couple
of reasons. This is a study which explores the use of a PD-L1
inhibitor, durvalumab, alongside either the R-CHOP regimen or the
R2-CHOP regimen in patients with newly diagnosed high-risk diffuse
large B-cell lymphoma. And this includes patients with double-hit
lymphoma where we know the prognosis is particularly bad.
These are very preliminary data in which a standard therapy with
R-CHOP or R2-CHOP is being modified by the addition of this
anti-PD-L1 monoclonal antibody. At the moment, the data are very
largely related to adverse events. And there are some very
preliminary outcome data, but probably difficult to read anything
very much into those.
The interest, to my mind, is that some recently-published data have
suggested that checkpoint inhibitors in aggressive B-cell lymphoma
may not be a particularly effective treatment modality. But I think
it will be very interesting to see whether the combination of
checkpoint inhibitors plus regular chemotherapy have the
opportunity to improve outcome.
So I think this is a study in progress. It's way too early to draw
any conclusions at the moment. But I do think it's important not to
write-off the role of checkpoint inhibitors in aggressive lymphomas
without conducting important studies like this one which look at
combination therapies rather than just the single-agent
therapy.
And then, in conclusion, one other study which I think is quite
important, again, presented in poster form, and this was a study
that looked at survival disparities of diffuse large B-cell
lymphoma in a community-based cancer center. And essentially, this
was a retrospective study which looked at 381 patients who had
aggressive lymphomas and looked at outcome according to race and
showed very highly significant disparity in survival for those
patients who were African American where their overall survival was
markedly inferior to other patients with a hazard ratio of
2.19.
So it was a really very marked difference in outcome. The
explanation for this is not entirely clear from the abstracts. But
I think it's something which is very important for us to take note
of.
So that is just a quick run-through some of the poster
presentations that caught my eye at the meeting this year. I think
that there will be some important practice-changing studies
presented during the oral presentations. And I would certainly
strongly encourage folks to be at those. But I think that, as
always, there are some important highlights in the poster
presentations. And I could go on with many more, but I think that
those probably be the highlights from my perspective.
Sounds like some promising studies to look forward to. Again, today
my guest has been Dr. John Sweetenham. Thank you for being on our
podcast today.
Thank you. Great to have the opportunity to talk.
And to our listeners, thank you for tuning into the ASCO Daily News
podcast. If you're enjoying the content, we encourage you to rate
us and review us on Apple podcast.