Preserving a Future Family: Dr. Mary Lopresti on Oncofertility

04/11/19 • 6 min

Mary Lopresti, DO, is a hematologist oncologist with the Lifespan Cancer Institute, where she treats patients who have breast and gynecologic cancers. Most of her patients are younger than 42 years.

Welcome to the ASCO Daily News podcast. I'm Lauren Davis. And joining me today is Dr. Mary Lopresti, a hematologist/oncologist with the Lifespan Cancer Institute, where she treats patients who have breast and gynecologic cancers. Most of her patients are younger than 42 years. Dr. Lopresti, welcome to the podcast.
Oh, thank you so much, Lauren, for having me today.

We're glad you're here. Today we're talking about issues around fertility and how cancer can present challenges to women who want to be able to get pregnant and grow their families. Because you treat younger patients, at what point in the diagnosis process do you mention fertility options such as egg freezing?

Well, we've made it our practice at Lifespan to discuss this at the first touch point with the patient. So our young women who are newly diagnosed with breast cancer will come in to a multidisciplinary clinic, and so they'll need a breast surgeon, medical oncologist, radiation oncologist. And besides from talking about their new diagnosis and management, at that point, we'll also ask them if they plan on growing their family or having another baby or a baby. And at that point, we'll ask them if they would desire fertility preservation. And so we really from day 1 of meeting them will explore that option.

What are some of the struggles in helping patients navigate cancer care when they also have to decide whether or not they want to preserve their fertility?

I think this biggest struggle is timing, trying to help this woman decide on her breast surgical options, discuss genetic testing. And many of these young women have aggressive breast cancers requiring chemotherapy, so it's the timing of when we give the chemotherapy. And then if we are planning to give chemotherapy, how does fertility fit in?

Many times, I think physicians shy away from mentioning fertility because there's a delay in chemotherapy, which is so important. And so we've tried to get that timing down a little bit better by developing an algorithm to get that woman to a fertility specialized in a streamlined manner, and that has helped us navigate these young women a little bit better.

What advice do you have for physicians who ideally would mention fertility preservation but sometimes leave it out because of the patient's need to start treatment such as chemotherapy as you mentioned immediately?

Well, I think that it's very understandable for an oncologist to feel like they need to leave it out if a young woman has large tumor burden and they're very worried about starting systemic therapy. But yet, I think it's really up to us as physicians to make sure that the patient has informed consent. And ASCO has published guidelines for preservation so that we can help educate our patients on what options that they have. And I think we need to continue to try to do that and put our own worries aside.
Are there patients for whom you do not recommend fertility preservation? And how do those conversations go?

I'd say in general, no. I think we offer it to anyone who desires to have a pregnancy in the future. Again, there's always a worry in a woman who has an estrogen positive breast cancer, a large tumor, bulky lymph node disease to recommend fertility preservation because the concern has generally been that you could stimulate very high levels of circulating estradiol level with preservation. But now with letrozole, which is an aromatase inhibitor, and tamoxifen, there are ways to decrease the estradiol level and still get mature follicles as well. So I think that we do recommend fertility preservation everyone.

And then just moreover on that point is that there was a recent study by Rodriguez-Wallberg and colleagues. It was a Swedish match cohort trial. And so they looked at women undergoing fertility preservation compared it to age match controls, and there was not an increase in the risk of recurrence with fertility preservation. So it's a generally safe and can be done in about a two-week period.
That's wonderful. What do you see for the future of cancer care in oncofertility?

I think our knowledge will continue to increase as newer drugs come on the market. I think we should all be concerned about fertility because we're not going to know how they affect fertility in the mechanisms there. So I think as physicians, we have to become more educated, and I think we're going to see more physicians talking to their patients. I think we're going to see more patients having access to educational materials or looking on social media for decision trees to help them with fertility preservation.

I think we're ...

Mary Lopresti, DO, is a hematologist oncologist with the Lifespan Cancer Institute, where she treats patients who have breast and gynecologic cancers. Most of her patients are younger than 42 years.

What are some of the struggles in helping patients navigate cancer care when they also have to decide whether or not they want to preserve their fertility?

I think we're ...

Previous Episode

Dr. Marco Davila Discusses How CAR T-Cell Therapies in B-Cell Malignancies Show Promise for Other Cancers

Dr. Marco Davila Discusses How CAR T-Cell Therapies in B-Cell Malignancies Show Promise for Other Cancers.

I'm Lauren Davis. And joining me today is Dr. Marco Davila a medical oncologist in the Department of Blood and Marrow Transplantation and Cellular Immunotherapy at Moffitt Cancer Center. His clinical focus is utilizing cell therapies to treat patients with hematologic malignancies. Dr. Davila, welcome to the podcast.
Thanks so much for the invitation.

Today we're talking about CAR-T therapies and B-cell malignancies. Your work with targeted therapies in leukemias and lymphomas has grant great promise for patients who, historically, we would not expect to have seen such sustained responses. What do you attribute these response rates to?

Well, this is really a tremendously novel therapy. These patients that have been approved for this therapy have been deemed to be chemotherapy refractory, meaning kind of the standard treatments that you'd give these patients, the patients' malignancies have become well adapted to or are able to evade the treatments. So the immunotherapies that are being applied for these B-cell leukemias and lymphomas really are a complete paradigm shift for medical oncology as well as for the patient's cancers. So these patients' cancers, while they've been well-adapted to chemotherapies, they have not been adapted so well to CAR T-cell therapy.

Can you walk me through the process of obtaining these therapies? What's the general timeline?

Sure, so the first thing we have to do as a medical oncologist is determine that the patient is eligible for the CAR T-cell therapy, if they meet the indications in the label provided by the FDA and the drug manufacturer. So that involves mainly making sure that they have the diagnosis of an aggressive B-cell lymphoma and/or a B-cell acute lymphoblastic leukemia that has relapsed and received at least one prior therapy. So once we deem that the patient is eligible for therapy, we then arrange for the patient's peripheral blood mononuclear cells, and more specifically, T-cells, be isolated from their blood.

So this involves a apheresis procedure, where the patient comes in, usually has the large-bore needle inserted in one arm to collect the blood. It goes through a machine, filters out the cells, and returns the blood through another large-bore [INAUDIBLE] needle in the patient's other arm. So this procedure can last several hours. But afterwards, billions of cells are sent to the manufacturer for isolation of T-cells, and then genetic retargeting to the CD19 antigen present on the patient's B-cells, malignant B-cells.

Amazing-- what other cancers can be targets in the future?

So the initial approvals, as I said, have been for B-cell acute lymphoblastic leukemia and aggressive B-cell lymphoma, but there is very promising late-stage data targeting multiple myeloma, targeting the B-Cell Maturation Antigen, BCMA. And I think many of us expect that myeloma will get an approval for this treatment with BCMA-targeted CAR T-cells sometime in the next year or so. And that's going to really represent another kind of big change to a medical oncology and bone marrow transplantation programs throughout the US.

And that's because two of the major indications for autologous stem cell transplantation, so auto stem cell transplants, are aggressive B-cell lymphomas and myelomas. So many of these patients that standardly would receive an autologous stem cell transplantation may in fact be candidates for CAR T-cell therapy instead. So while myeloma is next in line, I think there's a lot of interest in adopting this technology later to, or hopefully shortly to acute myeloid leukemia as well.

What are some of the obstacles in applying this technology at a cancer center?

Well, I think probably one of the biggest obstacles is that there is a time of production, a time of [? TCQA ?] analysis to make sure that the product that's been made is safe, is not contaminated or anything like that. And sometimes the production time and the [? TCQA ?] time could be short, maybe about two to three weeks. Sometimes this lasts longer than a month.

And as I said earlier, in terms of the indications for this therapy, aggressive B-cell leukemias and lymphomas that are chemotherapy refractory, that these are patients that can't necessarily wait months for a product. So that I think is probably the biggest challenge, to be able to see a patient in the clinic and go, yes, you have very bad aggressive leukemia and lymphoma. And you meet this indication for this therapy. So we're going to collect the cells. And you know, we'll see you sometime in a few weeks or in a few months when the product is ready. That's probably the biggest challenge.

I think, luckily, for some of these products, it seems that t...

Next Episode

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, ...