Talking about the results as Christine mentioned, the response base was actually very appealing; it was 61% of all treated patients and 74% were for [per protocol set]….. Those are the patients who received 4 weeks or more on protocols; 74% had a response. We did see improvement in hemoglobin, a decrease in LDH [lactate dehydrogenase], and an increase in platelets as well. All the laboratory criteria showed improvement on those populations.

In terms of survival, for all patients at the 100% or 60% survival rate and for patients who received 4 weeks or more of treatment on the trial, there was an 83% survival grade. Patients who had response among those patients exhibit a 94% survival rate.

The overall survival for patients who had for the full-set analysis was 274 days, and…set population was 361, and responders was not reached at the time of analysis. This is really compelling data for this molecule; I don't know whether Jeff or Hari have any comments on the results.

I agree, they're very encouraging. We have very little to treat these patients with, and as Christine said, the more of the better. It's great to see that this study was run.

Same thing. I think the availability of pathophysiologically targeted agent addresses what really is at the bottom of the problem, and it is a much better safety profile than some of the other agents that we have; that's the attraction. Plus we are talking about a situation very similar to second or third line treatment of GVHD [graft versus host disease] where everything is a 20% to 30% drug and suddenly we have a high response rate in the 60% to 90% range, depending on how it was used. That's actually a really good move. How often is it administered?

 It is being administered on a weekly basis; these patients usually are very sick and are in the hospital. The first dose or couple of doses are administered in hospital, however I have patients who were discharged and started receiving the treatment as outpatient without any problem.

Jeff, do any other comments on the treatment?

No; just in general we need more information on defibrotide that was mentioned. In terms of other therapies, there are several other experimental anticomplement therapies that are out there being tested on other complement mediated disorders. As far as I know, there is nothing else that is being specifically looked at in the TA-TMA [transplant-associated thrombotic microangiopathy] setting, and it looks really good for narsoplimab.

The defibrotide trial was, as Hari alluded to, a very small patient population. I discussed with the company about this trial and there was about a 50% response rate, but it's a small number of patients. In some of the patients they had a combination of defibrotide with other agents; that makes it very hard to have a solid conclusion on defibrotide use. I think that that would be a good agent to test in the future prospective study.

I would like to thank all of you for this really nice and rich informative discussion. Before we conclude I would like to get some final thoughts from each of you on the exciting new development and emerging agents. We'll start with Dr Duncan.

I think I get the easy choice; I get to go first. The emerging agents’ discussions have been really rich, but I were to ask or hope that people take away one thing from this discussion is to think about TA-TMA; think about your labs, look at your LDH…. If we're not thinking about it, as Dr Hari said, we can't treat it. The most important thing is to really have awareness and think about this as a significant complication of transplant.

Yes; I agree with what Dr Duncan just said, but I'm excited that now we have agents that are targeted at the pathophysiological mechanism of the disease. We also have other complement (inaudible) antibodies (inaudible), all of which bode well for this complication.

I agree; think about this disorder more and you're going to save people that way. Think about the pathophysiology; don't just tread water doing things like plasma exchange or Rituxan [rituximab] unless there's a specific indication for an auto-antibody present. Think about trials of these newer experimental agents which look very promising.

Once again, thank you very much for participating in this rich discussion. To our viewing audience, we hope you found this 

 discussion to be useful and informative. Thank you.

Videos

The panel of transplant experts discuss the results of the phase 2 trial of narsoplimab and the pending FDA approval of this agent for treatment of transplant-associated of thrombotic microangiopathy.

Narsoplimab Trial Results 

Christine N. Duncan, MD, a senior physician at Dana-Farber Cancer Institute, and assistant professor of pediatrics, Harvard Medical School, discusses the expansion of CAR T-cell therapy in oncology.

Since its inception in B-cell acute lymphoblastic leukemia (ALL), it is exciting to see CAR T-cell therapy expand to other malignancies and patient populations, says Duncan. It is also encouraging to see products being developed that target more than CD19, as patients with CD19-targeted disease treated with CD19-directed CAR T-cell therapy ultimately relapse with CD19-negative disease. Now, there are data showing that CAR T cells can be used to target both CD19 and CD22.

Beyond that, there's a population of patients who have relapsed T-cell ALL, who until recently, were unable to receive CAR T-cell therapy, says Duncan. Those patients have a poor survival rate after relapse of approximately 28% or less. It's exciting to see CAR T-cell studies developing and expanding to include very high-risk patient populations. In keeping with the current pace of progress, investigators are hopeful that CAR T-cell therapy will expand to entirely new populations.

Dr. Duncan on the Expansion of CAR T-Cell Therapy

Christine N. Duncan, MD, senior physician, Dana-Farber Cancer Institute, assistant professor of pediatrics, Harvard Medical School, discusses the use of CAR T-cell therapy in the treatment of pediatric patients with acute lymphocytic leukemia (ALL).

The FDA label for the use of CAR T-cell therapy in pediatric oncology is indicated for patients with relapsed/refractory high-risk ALL. With the FDA approval of CAR T-cell therapy, physicians continue to compound the success of treatment for pediatric patients, says Duncan. In the early 1970s, the overall survival (OS) rate was 58%. Now, the OS rate is approximately 90%.

Although the survival rate is high, a percentage of patients will relapse or become refractory to their initial therapy, says Duncan. These patients have a poor prognosis with a survival rate closer to 20%, she adds. Notably, a lot of the work regarding CAR T-cell therapy stemmed from initial research targeting CD19 in pediatric oncology. Since its expansion to adult patients and other tumor types, investigators are learning more about obstacles with the therapy as well as patient selection, Duncan concludes.

Christine N. Duncan, MD

Articles

Narsoplimab Trial Results

Dr. Duncan on the Expansion of CAR T-Cell Therapy

Dr. Duncan on the Use of CAR T-Cell Therapy in Pediatric ALL