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Case Study 2: Options for Biochemically Relapsed MM

Insights From: Rafael Fonseca, MD, Mayo Clinic; Gareth Morgan, MD, PhD, UAMS Myeloma Institute; Thomas G. Martin, MD, UCSF Helen Diller Family Comprehensive Cancer Center
Published: Wednesday, Mar 07, 2018



Transcript: 

Gareth Morgan, MD, PhD: When you choose a treatment for an older patient, it’s very, very important to consider that patient’s life, their frailty, and their side effect profile. This patient has been on a relatively low dose of lenalidomide, so it would be possible to increase the dose of that in the first instance and expect to get 6 to 8 months’ better disease control. That’s one option. You could swap to a drug with a different mode of action. Adding in a proteasome inhibitor would be expected to work. Depending on the rate of progression, and this is an indolent progression, you could add in an oral proteasome inhibitor like ixazomib. If the disease was more explosive, then using the most effective proteasome inhibitor would be the best strategy, using carfilzomib.

The other thing you could do now would be to add daratumumab into the regimen that they’re on. What you really don’t want to do is beat up somebody of that age. What you’re trying to do is give them good quality of life as well as duration of life. So, you should always enter into a discussion with the patient and harmonize your therapeutic choice with what they want. Sometimes, they want to come into the hospital for injections because they get a companionship from nurses and people in the hospital; sometimes they want to be at home. They may live 100 miles away and want to continue doing gardening, and so the therapeutic choice becomes very clinical.

It’s difficult to recommend any specific regimen for this indolent type of progression. I’ll take any of the options I outlined based on discussion with the patient. There are some clearly important things though. You shouldn’t aim for the maximum dose in an older patient. It’s important to choose a dose that they tolerate because they get the benefit of being on it for a prolonged time. If you maximize the dose and they only stay on it for 3 months, they can’t possibly benefit from it. There are also important lessons about doublets versus triplets. An effective triplet in this age group is well tolerated. Even though they’re older, aiming for a triplet is probably a better strategy than just a doublet. So, you have a whole variety of clinical options in this setting.

Rafael Fonseca, MD: In the patient who presented here, we’re going to consider everything. We’ll consider the biology of the disease, including the genetic factors that we mentioned previously. We’ll consider comorbidities. We’ll also consider tolerance to prior therapy and patient wishes and try to incorporate all of that information together. One thing we might do in 2017 that we would not have done 3 years ago for someone who has a t(11;14) is actually use off-label venetoclax in these patients. Venetoclax turns out to have some very interesting activity in patients who have a more lymphoid morphology. They are enriched among those who have t(11;14).

We actually have done that in our practice quite successfully. If someone is 81, you would be able to do that. That could be an option to be considered. Now, traditionally, this is reserved for farther down the line after a person has exhausted therapy. Normally, you would think this person could get a carfilzomib-based combination or they could get daratumumab in combination, perhaps with pomalidomide. But I would say the wild card there would be that a lot of people are starting to consider the use of venetoclax in situations like this.

Thomas G. Martin, MD: In this patient who is older, received standard lenalidomide and dexamethasone as her primary therapy and lenalidomide maintenance, and now has relapsed, there are a few things that we need to consider when choosing her next therapy. First is the drug dose of lenalidomide at maintenance. I’d bet that she was on 10 mg of lenalidomide maintenance, and then I would probably not use lenalidomide as my next therapy. I would consider her refractory to lenalidomide.

I like to use an IMiD-based therapy and then, when they relapse, I would choose a proteasome inhibitor–based therapy. For this woman with some renal insufficiency, I think a great option for therapy would be bortezomib, cyclophosphamide, and dexamethasone, or VCd. I think that’s a great regimen at relapse. She also would be a candidate for oral pomalidomide if we were looking for an oral regimen. Of all the preferred regimens from the NCCN guidelines, including daratumumab/Revlimid/dexamethasone; elotuzumab/Revlimid/dexamethasone; and daratumumab/Velcade/dexamethasone, all of those are potential therapies for this patient. But I would probably go with either VCd or pomalidomide as the next therapy.

In an older patient, you really need to consider supportive care measures. I think there are 4 supportive care measures that she needs. First, she needs bone health. For her bone health, she needs calcium and vitamin D. If she hasn’t had bisphosphonates, I certainly would give her a year of bisphosphonates at monthly dosing or consider 2 years of every-3-month-based dosing. That’s my personal practice.

The second thing is that she needs infectious disease prophylaxis. Any time patients are on a proteasome inhibitor or on any dexamethasone, shingles can recur. Around 10% of patients develop shingles if you don’t put them on prophylaxis. So, they need acyclovir for prophylaxis.

The third thing is to improve their blood counts, especially in a patient who has renal insufficiency. She has baseline renal insufficiency. She may be anemic due to low EPO levels. I would have no problems putting this patient on erythropoietin to try to stimulate the growth of her red cells and to try to keep her hemoglobin above 10 g/dL. I think patients, especially 80-year-olds, feel much better if their hemoglobin is between 10 g/dL and 12 g/dL rather than less than 10 g/dL.

Lastly, if I am going to put them on an IMiD-based therapy, I do want to make sure that I’m preventing blood clots. There are a variety of strategies that can be used. Most commonly, I use aspirin alone as a single agent. But we can use Lovenox (enoxaparin sodium) as prophylaxis. There are some studies that are going to evaluate the factor Xa inhibitors, or other next-generation anticoagulants, in this patient population, which I think would be a big success in these types of patients.

Transcript Edited for Clarity 
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Transcript: 

Gareth Morgan, MD, PhD: When you choose a treatment for an older patient, it’s very, very important to consider that patient’s life, their frailty, and their side effect profile. This patient has been on a relatively low dose of lenalidomide, so it would be possible to increase the dose of that in the first instance and expect to get 6 to 8 months’ better disease control. That’s one option. You could swap to a drug with a different mode of action. Adding in a proteasome inhibitor would be expected to work. Depending on the rate of progression, and this is an indolent progression, you could add in an oral proteasome inhibitor like ixazomib. If the disease was more explosive, then using the most effective proteasome inhibitor would be the best strategy, using carfilzomib.

The other thing you could do now would be to add daratumumab into the regimen that they’re on. What you really don’t want to do is beat up somebody of that age. What you’re trying to do is give them good quality of life as well as duration of life. So, you should always enter into a discussion with the patient and harmonize your therapeutic choice with what they want. Sometimes, they want to come into the hospital for injections because they get a companionship from nurses and people in the hospital; sometimes they want to be at home. They may live 100 miles away and want to continue doing gardening, and so the therapeutic choice becomes very clinical.

It’s difficult to recommend any specific regimen for this indolent type of progression. I’ll take any of the options I outlined based on discussion with the patient. There are some clearly important things though. You shouldn’t aim for the maximum dose in an older patient. It’s important to choose a dose that they tolerate because they get the benefit of being on it for a prolonged time. If you maximize the dose and they only stay on it for 3 months, they can’t possibly benefit from it. There are also important lessons about doublets versus triplets. An effective triplet in this age group is well tolerated. Even though they’re older, aiming for a triplet is probably a better strategy than just a doublet. So, you have a whole variety of clinical options in this setting.

Rafael Fonseca, MD: In the patient who presented here, we’re going to consider everything. We’ll consider the biology of the disease, including the genetic factors that we mentioned previously. We’ll consider comorbidities. We’ll also consider tolerance to prior therapy and patient wishes and try to incorporate all of that information together. One thing we might do in 2017 that we would not have done 3 years ago for someone who has a t(11;14) is actually use off-label venetoclax in these patients. Venetoclax turns out to have some very interesting activity in patients who have a more lymphoid morphology. They are enriched among those who have t(11;14).

We actually have done that in our practice quite successfully. If someone is 81, you would be able to do that. That could be an option to be considered. Now, traditionally, this is reserved for farther down the line after a person has exhausted therapy. Normally, you would think this person could get a carfilzomib-based combination or they could get daratumumab in combination, perhaps with pomalidomide. But I would say the wild card there would be that a lot of people are starting to consider the use of venetoclax in situations like this.

Thomas G. Martin, MD: In this patient who is older, received standard lenalidomide and dexamethasone as her primary therapy and lenalidomide maintenance, and now has relapsed, there are a few things that we need to consider when choosing her next therapy. First is the drug dose of lenalidomide at maintenance. I’d bet that she was on 10 mg of lenalidomide maintenance, and then I would probably not use lenalidomide as my next therapy. I would consider her refractory to lenalidomide.

I like to use an IMiD-based therapy and then, when they relapse, I would choose a proteasome inhibitor–based therapy. For this woman with some renal insufficiency, I think a great option for therapy would be bortezomib, cyclophosphamide, and dexamethasone, or VCd. I think that’s a great regimen at relapse. She also would be a candidate for oral pomalidomide if we were looking for an oral regimen. Of all the preferred regimens from the NCCN guidelines, including daratumumab/Revlimid/dexamethasone; elotuzumab/Revlimid/dexamethasone; and daratumumab/Velcade/dexamethasone, all of those are potential therapies for this patient. But I would probably go with either VCd or pomalidomide as the next therapy.

In an older patient, you really need to consider supportive care measures. I think there are 4 supportive care measures that she needs. First, she needs bone health. For her bone health, she needs calcium and vitamin D. If she hasn’t had bisphosphonates, I certainly would give her a year of bisphosphonates at monthly dosing or consider 2 years of every-3-month-based dosing. That’s my personal practice.

The second thing is that she needs infectious disease prophylaxis. Any time patients are on a proteasome inhibitor or on any dexamethasone, shingles can recur. Around 10% of patients develop shingles if you don’t put them on prophylaxis. So, they need acyclovir for prophylaxis.

The third thing is to improve their blood counts, especially in a patient who has renal insufficiency. She has baseline renal insufficiency. She may be anemic due to low EPO levels. I would have no problems putting this patient on erythropoietin to try to stimulate the growth of her red cells and to try to keep her hemoglobin above 10 g/dL. I think patients, especially 80-year-olds, feel much better if their hemoglobin is between 10 g/dL and 12 g/dL rather than less than 10 g/dL.

Lastly, if I am going to put them on an IMiD-based therapy, I do want to make sure that I’m preventing blood clots. There are a variety of strategies that can be used. Most commonly, I use aspirin alone as a single agent. But we can use Lovenox (enoxaparin sodium) as prophylaxis. There are some studies that are going to evaluate the factor Xa inhibitors, or other next-generation anticoagulants, in this patient population, which I think would be a big success in these types of patients.

Transcript Edited for Clarity 
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