What is induction therapy?

What is induction therapy? How long is induction therapy? Should induction therapy be a set number of cycles or based on treatment response?

So induction therapy is the initial multi-agent therapy used to get the disease under control.

We sort of have stolen the language from AML or acute leukemia. When you talk about remission induction.

The goal is to induce a remission.

So induction therapy in this case and do some response as deep as possible.

I mean, again, it tends to be the more intensive period of time both for side effects and for disease response.

And it tends to be the time when you're going to see your doctor the most frequently—me or the nurse practitioner or, you know, the nurses in the clinic.

In an attempt to really make sure that we've got the patient locked in, knowing what treatment they should be getting, make sure we're managing and jumping all over toxicity so that we don't harm patients.

And so that it's that period of time that is the most intensive.

But that's sort of the general idea about what is induction.

So induction therapy is pretty much the first round of therapy that you get for newly diagnosed myeloma patients.

The goal of induction therapy is to reduce the tumor burden, improve your symptoms and hopefully induce some kind of deeper remission.

So we have increasing data that you see it. If you are able to attain a deeper response with induction therapy, the outcome is better.

So when a patient is newly diagnosed, induction therapy is how you're going to get rid of those myeloma symptoms and reduce the level of the cancer.

So the goal is first and foremost, what brought this patient to diagnosis? Hypercalcemia, increased calcium, kidney problems, anemia or bone disease.

The so-called CRAB symptoms, which have a devastating impact on a patient's quality of life.

So we have to reverse those promptly.

And the way we know we're doing that is obviously those symptoms should improve.

But luckily in myeloma, it's a disease where we have easy lab tests to tell us we don't need to do imaging every so often.

Imaging is part of the evaluation, but we don't have to wait for that every month. We should be. And then sometimes even more frequently.

But at a monthly level, you can measure the myeloma markers. All the proteins that manifest with the diagnosis.

And we can see that we're chipping away at it.

And of course keeping in mind the side effects.

But the goal of induction therapy is to really get rid of those symptoms and knock the myeloma down as low as you can get it.

Induction therapy refers to the initial therapy of multiple myeloma, and it's usually a combination regimen with either 2 or 3 or, more recently, four drug regimens.

The therapies are usually a combination of oral medications and other medications that are either given intravenously or subcutaneously.

Regimens are given in repeating cycles that range in length from 3 to 4 weeks.

For younger or more fit patients after 3 or 4 cycles of induction therapy, typically, a patient will proceed to high dose chemotherapy with autologous stem cell transplants. For less fit patients who aren't headed to transplant, induction therapy may consist of 6 to 8 cycles of the initial regimen before moving on to maintenance therapy.

The different induction therapy that is used in the United States includes the following.

The first one is a standard regimen of Velcade or a proteasome inhibitor, Revlimid or immunomodulatory agent, and dexamethasone. It's called VRd.

That is the most commonly adopted induction regimen in the United States.

Then we have modifications of it where we can add a CD38 monoclonal antibody like daratumumab or Isatuximab to the combination of VRd.

The idea is that if you can use four drugs, it will help our patients go into deeper remission and hopefully improve survival.

The other induction regimens that are also used in our setting is Velcade, Cytoxan, and Dex.

It is used in selected patients who cannot get Revlimid, such as patients who have renal failure.

The induction therapy in patients who are frail or otherwise ineligible for transplant is a bit different.

Again, VRd is the very acceptable regimen for patients who don't.

There is no intention for often transplant and VRd stands for Velcade, R for Revlimid, and D for dexamethasone. Frail patients where they cannot take VRd.

There is a modification of the regimen called VRd-lite whereby the dose of Revlimid is actually reduced from the conventional standard VRd regimen.

Patients who are frailer where a triplet regimen of VRd is not feasible, a doublet regimen of a lenalidomide and dexamethasone is another acceptable regimen.

We know that CD38 monoclonal antibody is kind of revolutionized the field of multiple myeloma.

So there are daratumumab along with the amide and dexamethasone was studied in the setting of patients who are frail and who could not go into an upfront transplant.

And that regimen is what we call the Dara RD or DRd. That's also another acceptable regimen in the setting of transplant ineligible patients.

Should induction therapy be a set number of cycles or based on treatment response?

The duration of induction therapy is guided by several factors. First is, is this person somebody that might be looking at transplant in their future?

Because we know that with some of the agents that we use, prolonged therapy can impact the collection.

So in particular, lenalidomide or Revlimid has been historically one such issue.

So more than 4 to 6 months. And we're now learning that the CD38 monoclonal antibody such as Dara may also affect it, perhaps not to the same extent.

But I think as a general rule, you want to try to collect cells within 4 to 6 cycles.

But beyond that, you can do additional cycles after you've collected to kind of get maximal reduction and then make that decision about transplant or not.

And I think that the transplant non-eligible or the non-transplant population, that's a little bit difficult to answer because it's not divided in that induction transplant consolidation, maintenance.

There's not that segmentation of the therapy in that same way.

So whatever you're starting, you kind of keep going with that and then try to reduce the intensity.

Once you've had a maximal remission.

But usually that duration of induction is more applicable to the transplant population.

Induction therapy is variably given for four to 6 to 9 cycles. This is or months depending on the regimen.

And there's no great research at this point telling us that you should get six cycles of induction therapy or nine cycles of induction therapy.

The old practice had been to treat to maximal plateaued response and then back down.

I think that's a reasonable approach. Depending on how aggressive the patient wants to be in their life circumstances.

Sometimes if we say we've had an inadequate response, that would alter therapy or intensify therapy before cutting the induction down to maintenance therapy.

And, and again, prior to stem cell transplant, that's also a point of debate, with some research showing that you do not need extended courses of induction therapy.

But some early data coming out of some UK studies implying that altering therapy for patients who've had an inadequate response to induction therapy actually leads to longer periods after the stem cell transplant of disease remission or progression-free survival.

And I think that this is an ongoing point of research.

So we don't know for certain.

But again, I think the standard approach is you're going to treat for somewhere around 4 to 9 cycles of therapy, depending on the clinical situation, followed either by a consolidation course and then maintenance therapy or backing down to maintenance therapy.