Myeloma Treatment Research Updates: Highlights From the 2018 ASCO and EHA Meetings

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Jack Aiello:

Doctors Krishnan and Richter, let me ask you another question.  In June it's always a big month, ASCO happens, the clinical oncology conference in Europe they have something similar, EHA.  Can you give us some insights?  I'll start with Dr. Krishnan.  What were some of the highlights that came out of those large cancer conferences for myeloma patients?   

Dr. Krishnan:

Sure.  So I had the honor of giving the ASCO highlights actually at ASCO and surprisingly we had a full house, which tells you the interest in myeloma. So the highlights in that session were really focused around relapsed myeloma, not surprisingly.  So combinations of venetoclax (Venclexta), the drug approved for CLL, using it combination with carfilzomib (Kyprolis), proteasome inhibitor, so we know venetoclax work the best when it is combined with proteasome inhibitor.  Most of the data we've had so far has been with bortezomib, so this was the first trial presenting the data with carfilzomib, and that included patients who have had prior bortezomib or who were bortezomib refractory.  So that was exciting.  

Jack Aiello:

Just to clarify, if patients aren't aware, bortezomib (Velcade) is the same thing as bortezomib.  

Dr. Krishnan:

Thank you.  

Jack Aiello:

Yep.  

Dr. Krishnan:

You know, the caveat in that trial was that patients had to be carfilzomib naive, so, you know, we clearly don't know when patients have had prior carfilzomib exposure if they received the same degree of response, but the response rates were very high, and patients who had a particular translocation that venetoclax targets, the (11;14) translocation, the response rate was 100 percent.  Again, these are small numbers of patients, but it is interesting data both in regards to the targeted therapy as well as in the idea that we can combine venetoclax with different agents.  

The other thing I would highlight was the CAR T?cell data, which I think of huge interest to patients. This is now an expansion cohort. So the initial data we saw was in about 20 patients.  Now we have data—it's still not huge numbers, 40 patients, but what we did see was that the response rates remain very high, about an 80 percent response rate.   

We learned some interesting things that previous trials and the CAR?T in this construct, the Bluebird trial, targeted BCMA.  And the initial phase of the trial required that the patient have a certain amount of BCMA expression on their plasma cells.  And that was actually a hard target to get.  Some patients were excluded.  What we learned in the expansion phase is that the percent of BCMA expression on the myeloma cells really didn't matter in terms of response. And that as an (?) Inaudible criteria is no longer an issue moving forward.   

We learned that the cell dose of T cells infused matters in terms of response, that there is a certain minimal threshold of T cells needed.  And we also did learn in terms of toxicity signals that we do see cytokine release.  Fortunately in the majority of patients it's been mild.  I would think those are the two biggest highlights.   

And the other one I wanted to briefly touch upon was the study looking at weekly carfilzomib.  So it looked at weekly compared to a traditional carfilzomib schedule, and showed that a weekly higher dose was tolerated well. Interestingly, we actually saw a better progression?free survival in the patients receiving weekly compared to the twice a week.  I haven't drilled down enough yet in that trial to know is that because of toxicity, or what are the reasons, but it just shows us that you can give weekly higher dose carfilzomib.   

Jack Aiello:

And, Dr. Richter, do you want to follow?up on any of those?   

Dr. Richter:

So those were absolutely the big highlights.  Everyone is very excited about the potential for CAR?Ts and myeloma.  

The other studies that I would high rights that came out of EHA and ASCO this year focused on combination therapies.  It is still a goal if we can in patients to put them on multi?drug combinations using multiple different mechanisms of action to treat the different types of subclones within the disease.  So there has been data recently on three? and four?drug combinations and how they may benefit patients.  

So the combination of elotuzumab (Empliciti), pomalidomide (Pomalyst) and dexamethasone (Decadron), the data was presented at EHA and was very encouraging as a really great option for patients with relapsed myeloma as well as that same combination, elotuzumab, pomalidomide and dexamethasone with bortezomib added to that.  A four?drug combination, but again in the right population this can be both tolerated and efficacious, as well as the three?drug combination of Velcade, pomalidomide and dexamethasone.  

And I know a lot of this may seem like, you know, they used to call it word salad where you're just mixing up different letters and combination and it doesn't all make sense, but that's part of what our collective job here is to look at all the different options and all the data and drill that on what the exact correct regimen is for an individual patient.  For some patients four or three drugs may be too many and two drugs may be appropriate, but in the right patients we may need to combine three or even four drugs to get the response needed.   

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.