Multiple Myeloma - Episode 6

Case 2: Determining Risk in Myeloma

December 23, 2019


Ola Landgren, MD, PhD:How would you deal with the topic of prognosis in the current era, Ajai? How would you discuss that with this patient?

Ajai Chari, MD:I always remember that I had a medical school class many years ago. The title of this elective was, Is it Cancer, and Can I Still Have Sex? The 2 questions that patients had but were afraid to ask. The point of that class was that 50% of what we tell patients, especially in the first visit, goes in 1 ear and out the other. Especially when you get to prognostication, it’s very important to use the right terms and frame the question. First of all, prognosis always applies to large populations, not an individual.

We can say that on average, this is what might happen for a high-risk or standard-risk patient, but there’s no guarantee. To that point, whatever we prognosticate, I always tell patients what’s more important than what we prognosticate at their first visit is what actually happens. And that’s functional risk. If you’re predicted to be high risk and your remission is lasting for a long time, you’re not as high risk as we thought you were. Conversely, if you were a low-risk patient and you relapse within a year of starting your induction therapy, that’s high risk regardless of what you were classified as. That said, I think this patient, by ISS [International Staging System], LDH [lactate acid dehydrogenase], FISH [fluorescence in situ hybridization] is showing not only t(4;14) but the deletion 17p in a high percentage. I think that’s another important topic: clonal burden and allele burden matters for 17p. Is it monoallelic or biallelic deletion? How many cells have that loss of 17p? These are all important concepts. But this patient would be a high-risk patient, I think, by whatever methodology. Hopefully we would all agree to treat this person aggressively.

Ola Landgren, MD, PhD:But you still kind of give this perspective that these are probabilities. We know there are patients with t(4;14) who are stage III in terms of burden. We know with all the new drugs, and we have the new combinations, that we can deplete the burden of disease in a few cycles with the modern therapies. But maybe the 17p deletion, or 1 allele, if there is a mutation on the other allele—that would be the biallelic inactivation of p53—that would probably be a bad prognosis. But we don’t know that patient data here. It’s just a probability.

Ajai Chari, MD:That’s correct.

Ola Landgren, MD, PhD:I agree. Do you have any other way of communicating risk?

Alfred Garfall, MD:No, I agree with everything Ajai said. I think for patients who want to know about their prognosis, it’s appropriate to tell them that you’re worried that you may not be able to keep their disease under control for as long as some other patients. But you should also emphasize that in 2019, we can make this patient feel better and treat them and have every expectation that they’ll respond to therapy. And as you said, we all have these patients who have very bad prognostic features, who nonetheless do better than we would expect. We always want to hold out hope for them.

Ola Landgren, MD, PhD:I’m sure we have had, Nina, patients come in 5 years later saying, “Do I still have high-risk disease? The doctor told me that the first time, but the disease has never really been bad.”

Nina Shah, MD:Right. By definition, clinically, they don’t have high-risk disease if they have made it 5 years. But I do think that [we] see a lot of myeloma patients, and a lot of times the patients have been referred—even from their primary doctor or primary oncologist—and no one had the result of the FISH. Now, with twenty-twenty hindsight, it is our job to tell this patient about the risk. The reason for that is they may never hear it if they don’t hear it from us. It’s a hard conversation to have, but if I was sitting in that chair, I wouldn’t want to have not been told this information. I always want to give as much information as I can. I agree with you, Ajai, that it’s really, really hard to process Kaplan-Meier curves and statistics in that first appointment when they’re just like a deer in the headlights. It’s really tough. It’s on us to communicate this effectively and repeatedly. And clinical trials. Al and I like this population for up-front CAR T [chimeric antigen receptor T-cell therapy], for example. We hope that clinical trials address this population.

Ola Landgren, MD, PhD:All these prognostic tests are not pregnancy tests. They are not determining pregnant or not pregnant. There’s like a little pregnant or a little less pregnant.

Nina Shah, MD:Which definitely does not exist.

Ola Landgren, MD, PhD:It would not really work in an OB-GYN situation. That would not be a really good test to have.

Transcript edited for clarity.