Treatment gaps
Few treatments options currently exist for patients with MDS, beyond erythropoiesis-stimulating agents for low-risk MDS and chemotherapy or transplant for high-risk MDS, as well as lenalidomide and luspatercept for specific subpopulations. With few breakthroughs occurring, Dr. Halpern expects that progress will only happen gradually, with new treatments coming primarily in the form of AML therapies.
“The biggest gap in our MDS regimen is treatment that can successfully treat or alter the natural history of TP53-mutated disease,” said Dr. Halpern, referring to an adverse risk mutation that can occur spontaneously or as a result of exposure to chemotherapy or radiation. “TP53-mutated MDS is very challenging to treat, and we have not had any successful therapy, so that is the biggest area of need.”
The most promising possibility in that area is an anti-CD47 drug called magrolimab, a drug being tested in a trial of which Dr. Halpern is a principal investigator. Not yet approved, magrolimab has been showing promise for AML when given with azacitidine (Vidaza) and venetoclax (Venclexta).
Venetoclax, currently used for AML, is another drug that Dr. Halpern expects to be approved for MDS soon. A phase 1b trial presented at the 2021 annual meeting of the American Hematology Society found that more than three-quarters of patients with high-risk MDS responded to the combination of venetoclax and azacitidine.
Unlike so many other cancers, MDS has seen little success with immunotherapy, which tends to have too much toxicity for patients with MDS. While Dr. Halpern sees potential for more exploration in this realm, she doesn’t anticipate immunotherapy or chimeric antigen receptor T-cell therapy becoming treatments for MDS in the near future.
“What I do think is, hopefully, we will have better treatment for TP53-mutated disease,” she said, while adding that there are currently no standard options for patients who stopped responding or don’t respond to hypomethylating agents.
Similarly, few new treatments have emerged for low-risk MDS, but there a couple of possibilities on the horizon.
“For a while, low-risk, transfusion-dependent MDS was an area that was being overlooked, and we are starting to see more activity in that area as well, with more drugs being developed,” Dr. Koprivnikar said. Drugs showing promise include imetelstat – an investigative telomerase inhibitor – and IRAK inhibitors. A phase 3 trial of imetelstat recently met its primary endpoint of 8 weeks of transfusion independence in low-risk MDS patients who aren’t responding to or cannot take erythropoiesis-stimulating agents, like Ms. Trueman. If effective and approved, a drug like imetelstat may allow patients like Ms. Trueman to resume some activities that she misses now.
“I have so much energy in my head, and I want to do so much, but I can’t,” Ms. Trueman said. “Now I think I’m getting lazy and I don’t like it because I’m not that kind of person. It’s pretty hard.”
Dr. Raza disclosed relationships with Epizyme, Grail, Vor, Taiho, RareCells, and TFC Therapeutics. Dr Ritchie reported ties with Jazz Pharmaceuticals, Novartis, Takeda, Incyte, AbbVie, Astellas, and Imago Biosciences. Dr. Halpern disclosed relationships with AbbVie, Notable Labs, Imago, Bayer, Gilead, Jazz, Incyte, Karyopharm, and Disc Medicine.