Treatment Options Are Expanding for Benign Hematologic Disorders

Kanwarpal S. Kahlon, MD

The treatment paradigms of aplastic anemia, immune thrombocytopenic purpura (ITP), and thrombotic thrombocytopenic purpura (TTP) have seen progress within the last year with the approval of eltrombopag (Promacta), avatrombopag (Doptelet), and caplacizumab-yhdp (Cablivi), in these indications, respectively. However, questions still remain and research is needed to develop more effective therapies for patients with these benign hematologic diseases, explained Kanwarpal S. Kahlon, MD.

"Aplastic anemia and transplant [need to be researched more], especially in people who may not have a matched sibling donor or even a matched unrelated donor," said Kahlon, an assistant clinical professor at the University of California, Los Angeles. "That is an area where there is an unmet need. Transplant can be very effective and seems to be better when given earlier, before donor specific antibodies develop."

In an interview during the 2019 OncLive^® State of the Science Summit^TM on Hematologic Malignancies, Kahlon discussed current treatment options for patients with aplastic anemia, ITP, and TTP, as well as future research for the field.

OncLive: With the agents available in aplastic anemia, what factors do you take into consideration when choosing which drug to give?

Kahlon: One of the big questions in aplastic anemia is whether you do transplant upfront. I'm sure some of my colleagues have an opinion about this, but part of it depends on how old someone is, how fit they are, whether they have a sibling donor, and if you can do testing quickly enough. That is a little difficult if someone is not in a transplant center where you can do human leukocyte antigen typing because that is often a very effective treatment upfront.

If that is not available, we give immunosuppressive therapy. What seems to be even better is immunosuppressive therapy plus eltrombopag because the response rates are higher than immunosuppression alone; relapses are also fewer. That's one of the big things that's difficult to determine whether someone should be transplanted immediately or not.

Additionally, depending on how well someone responds to immunosuppression, or say they don't respond, what are the options for transplant? If someone doesn't have a sibling donor, do you look for an unrelated donor or an alternative donor transplant? Those are some of the challenges. Not everyone with aplastic anemia responds well to transplant. There are people who don't engraft or their graft is rejected, which is also a very difficult situation.

Caplacizumab-yhdp has shown to be effective in treating TTP. Could you discuss your real-world experience with the drug?

It's a drug that, in acute TTP, prevents the interaction between the von Willebrand factor and platelets. It is effective at allowing platelet counts to come up, which is important if you're worried about bleeding, especially in someone who is not responding to standard treatment, plasma exchange, steroid, or something else. It's approved for frontline use.

When people with TTP come to the hospital, you start them on their treatment. You can use caplacizumab-yhdp upfront. It seems to be very effective in preventing relapse—especially early relapse—and it gives you time to adjust your immunosuppression so you can get their ADAMTS13 levels up. Hopefully, they do well for an extended period of time.

The patient that I used [caplacizumab-yhdp] in was in a similar situation. He wasn't newly diagnosed, but he was relapsing. He was basically not able to stay out of the hospital for any period of time. It was difficult to adjust his immunosuppression to get his ADAMTS13 level. We started [caplacizumab-yhdp]. It's a daily treatment of subcutaneous shots and is very well-tolerated. I don't think he had any real adverse events (AEs) because it interferes with the interactions between von Willebrand factor and platelets. A potential AE is bleeding, much like von Willebrand factor. The patient I treated had bleeding, but because his platelets stayed up, it gave us time to play around to get his immunosuppression right, so his ADAMTS13 levels came up and we could stop the caplacizumab-yhdp daily.

Now, he is doing very well; [caplacizumab-yhdp] will be particularly useful. [If a patient] is not responding to all the treatments that are being given, [caplacizumab-yhdp] is a very good and promising option.

Could you discuss the indications for eltrombopag and avatrombopag?

Eltrombopag is approved in chronic ITP and aplastic anemia treatment. Avatrombopag can be used in patients as a pre-procedure for patients with chronic ITP or chronic liver disease. If someone has one of those diagnoses, and they have low platelets and require surgery, [avatrombopag] can be used. It's effective, similar to eltrombopag, in bringing the platelets up.