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The Challenges of Long-Term Therapy

Insights From: Ajai Chari, MD, Icahn School of Medicine at Mount Sinai; Andrzej Jakubowiak, MD, PhD, University of Chicago; Sagar Lonial, MD, Winship Cancer Institute of Emory University
Published: Thursday, Jan 03, 2019



Transcript: 

Andrzej Jakubowiak, MD, PhD: Long-term treatment is difficult for everybody, for patients primarily. Even the concept of having a plan for long-term treatment when the patient is facing a first-time discussion about diagnosis and a plan for treatment is very hard to take. It seems endless, and that is overwhelming and sometimes difficult. But surprisingly to me, because I’ve been treating with extended treatment for many years, the majority of patients eventually accept this approach. If they have some difficulties with treatment, that is of course more difficult, but if they achieve good response, if we either have good tolerability of treatment or establish a schedule and dosing that are tolerable, not more than mild toxicities, if they see why we do that, for the most part they are able to stay in the program and continue on this treatment. But that’s for most of the patients, I would say, or for the majority of the patients who are tolerating treatment well, having good responses.

There are still challenges that emerge even for these patients for those who are having problems. If there are some emerging toxicities, difficulty tolerating the regimen, it’s of course much more difficult to stay on treatment and in the program or plan of therapy. That may be viably resolved between patient and physician, depending on what level of response it is, whether there is any way that we can limit those toxicities. The second difficulty is just frankly the natural human way of being in this type of a very hard, lifestyle-changing regimen. Coming sometimes even 2 to 3 times a week to the infusion area, not only for 5, 6, or 7 months but an extended period of time, is becoming harder and harder for many patients. Many of the programs take into account potential difficulty and scale back in various ways the intensity of treatment, which may be more intensive during the first 6 to 8 cycles, then becomes, in an extended phase, either once or twice a month in many of the current regimens, which is more doable.

Still, it is probably the most common challenge for both patient and physician to continue treatment for an extended time without problems, with this need for frequent visits and disruption of their normal life, especially if there are long waiting times, if there is a long drive to the clinic, especially on a clinical trial. So it is no question that this is a challenge.

Sagar Lonial, MD: As the survival of patients has improved markedly in the last decade, going from a survival of 2½ to 3 years, to at least in our data set, median survival has not been reached with 10-year follow-up. I think management of patients in the long term does become a bigger issue now. Clearly the use of bisphosphonates indefinitely is starting to fall out of favor. And so going with a frequency of every 3 months after a year or 2 and potentially stopping for patients who have long-term CR complete response is an important thing to consider to reduce the risk of ONJ [osteonecrosis of the jaw] and other complications of bisphosphonates.

The long-term use of maintenance therapy also becomes an issue. We have patients who have been on maintenance lenalidomide, I’d say, for 10-plus years. And at what point can you stop maintenance lenalidomide? The use of MRD [minimal residual disease] testing may help us to understand that, but right now we don’t have good data to help guide that decision.

Transcript Edited for Clarity
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Transcript: 

Andrzej Jakubowiak, MD, PhD: Long-term treatment is difficult for everybody, for patients primarily. Even the concept of having a plan for long-term treatment when the patient is facing a first-time discussion about diagnosis and a plan for treatment is very hard to take. It seems endless, and that is overwhelming and sometimes difficult. But surprisingly to me, because I’ve been treating with extended treatment for many years, the majority of patients eventually accept this approach. If they have some difficulties with treatment, that is of course more difficult, but if they achieve good response, if we either have good tolerability of treatment or establish a schedule and dosing that are tolerable, not more than mild toxicities, if they see why we do that, for the most part they are able to stay in the program and continue on this treatment. But that’s for most of the patients, I would say, or for the majority of the patients who are tolerating treatment well, having good responses.

There are still challenges that emerge even for these patients for those who are having problems. If there are some emerging toxicities, difficulty tolerating the regimen, it’s of course much more difficult to stay on treatment and in the program or plan of therapy. That may be viably resolved between patient and physician, depending on what level of response it is, whether there is any way that we can limit those toxicities. The second difficulty is just frankly the natural human way of being in this type of a very hard, lifestyle-changing regimen. Coming sometimes even 2 to 3 times a week to the infusion area, not only for 5, 6, or 7 months but an extended period of time, is becoming harder and harder for many patients. Many of the programs take into account potential difficulty and scale back in various ways the intensity of treatment, which may be more intensive during the first 6 to 8 cycles, then becomes, in an extended phase, either once or twice a month in many of the current regimens, which is more doable.

Still, it is probably the most common challenge for both patient and physician to continue treatment for an extended time without problems, with this need for frequent visits and disruption of their normal life, especially if there are long waiting times, if there is a long drive to the clinic, especially on a clinical trial. So it is no question that this is a challenge.

Sagar Lonial, MD: As the survival of patients has improved markedly in the last decade, going from a survival of 2½ to 3 years, to at least in our data set, median survival has not been reached with 10-year follow-up. I think management of patients in the long term does become a bigger issue now. Clearly the use of bisphosphonates indefinitely is starting to fall out of favor. And so going with a frequency of every 3 months after a year or 2 and potentially stopping for patients who have long-term CR complete response is an important thing to consider to reduce the risk of ONJ [osteonecrosis of the jaw] and other complications of bisphosphonates.

The long-term use of maintenance therapy also becomes an issue. We have patients who have been on maintenance lenalidomide, I’d say, for 10-plus years. And at what point can you stop maintenance lenalidomide? The use of MRD [minimal residual disease] testing may help us to understand that, but right now we don’t have good data to help guide that decision.

Transcript Edited for Clarity
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