| | | |  | Hello! Adam Feuerstein, Angus Chen, and Damian Garde here with our final dispatch from the annual meeting of the American Society of Hematology, live from New Orleans. Don't forget to sign up for our live ASH recap, scheduled for Wednesday. | | | 
Heaux heaux heaux (Adam Feuerstein) A second-generation BTK inhibitor takes the crown for treating CLL For years, a drug called ibrutinib, sold by Johnson & Johnson, was the mainstay for frontline treatment in chronic lymphocytic leukemia. It was far and away a better treatment than the chemotherapies that it replaced. “It’s the king on the block,” said Catherine Diefenbach, medical director of the lymphoma program at NYU Langone’s Perlmutter Cancer Center. “But it’s not the best drug anymore.”
The crown seems to be passing to another drug called zanubrutinib, made by BeiGene. At ASH today, researchers presented data that showed zanubrutinib has superior progression free survival over ibrutinib for patients with relapsed or refractory CLL. That, plus data showing that zanubrutinib has fewer toxicities and more patients were able to tolerate the drug for longer, suggested that doctors should eschew ibrutinib, made by AbbVie, in favor of zanubrutinib.
“I am not aware of a patient population in which I would select ibrutinib as compared to zanubrutinib,” Jennifer Brown, the lead author on the study and the director of the CLL center at the Dana-Farber Cancer Institute, said at a meeting with journalists.
Both drugs are known as Bruton’s tyrosine kinase inhibitors, drugs that hit a key B cell signaling pathway that leukemia cells need to grow and proliferate. Ibrutinib does more than just that, however, inhibiting over a dozen other proteins and causing a notorious toxicity profile that includes some cardiac toxicity. Second-generation BTK inhibitors like zanubrutinib or acalabrutinib, made by AstraZeneca, tend to be more precise.
Many doctors still use ibrutinib for CLL, and the FDA has not yet approved zanubrutinib for CLL. Some physicians are already prescribing zanubrutinib or acalabrutinib for the disease, though. “Occasionally, physicians may use it off label for CLL,” Brown said. “It depends on whether you can get it from insurance, and hopefully this data will help.”
Read more. | The value of real-world evidence in patient care Janssen Oncology is focused on using real-world evidence to complement clinical trial information to improve health outcomes for patients. Imran Khan, MD, PhD, US Vice President, Hematology Medical Affairs, and multiple myeloma patient advocate, Cindy Chmielewski, connected ahead of ASH 2022 to discuss the value of real-world evidence, the latest data that will be presented at the meeting across hematologic malignancies, and how the data allows us to bring needed options to patients. Learn more about the value of real-world evidence and Janssen Oncology’s data that will be presented at ASH. | With the addition of immunotherapy, ALL patients may be able to avoid transplant At the late-breaking abstract session today, Mark Litzow, a hematologist at the Mayo Clinic, presented data that suggested treating acute lymphoblastic leukemia patients with the bispecific antibody drug blinatumomab, sold by Amgen as Blincyto, might help patients dodge the need for allogeneic stem cell transplant. This usually happens once a patient’s ALL has been put into remission, but doctors suspect the leukemia is laying low in the bone marrow — even if the leukemia is not detected.
“They can still relapse,” Litzow said. “We know that there’s leukemia hiding in there.”
Transplants, at this point, can offer patients the chance to obliterate the last remaining vestiges of leukemia in their bodies. But it comes with risks like graft-versus-host disease, a condition in which transplanted cells attack the patient’s body. “Transplant is known to have long-term effects on quality of life, and there’s a mortality risk any time you send someone to transplant,” said Laura Michaelis, a hematologist-oncologist at the Medical College of Wisconsin who did not work on the study.
Litzow and his colleagues randomized 224 patients who had no minimal residual disease, meaning leukemia cells could not be measured in their body, to receive either blinatumomab and chemotherapy or chemotherapy alone. Those who received the chemo and the blinatumomab had a far greater chance of surviving, with an overall survival of 83% at three-month follow-up analysis, compared to 65% for those who only received chemo. That overall survival for the patients who got blinatumomab also plateaued at this level. “That means we hope the patients will continue to remain in remission and be cured,” Litzow said.
That also means the patients who responded might be able to avoid transplants. “One of my best friend’s son’s had this particular disease. He was MRD negative and died of graft-versus-host disease,” said Cynthia Dunbar, a hematologist at the National Institutes of Health who did not work on the study. “So, seeing this study is personally very meaningful for me. Unfortunately, it’s about two years too late.” | Novartis’ rare-disease drug beats Alexion blockbusters An investigative treatment from Novartis outperformed the standard of care, two top-selling medicines from Alexion Pharmaceuticals, in a pivotal trial enrolling patients with a rare blood disorder.
The drug, an oral treatment called iptacopan, dramatically increased hemoglobin levels and reduced the need for transfusions for patients with paroxysmal nocturnal hemoglobinuria, or PNH, a rare disorder in which the body produces defective blood cells that get attacked by the immune system, leading to severe anemia. The Phase 3 study enrolled about 100 patients, randomizing them to receive either iptacopan or one of Soliris and Ultomiris, two approved antibodies marketed by Alexion, now a division of AstraZeneca.
In data presented Tuesday, Novartis’ drug proved superior to the older medicines on its primary endpoints of increasing hemoglobin. Iptacopan also showed a statistically significant improvement on secondary goals of preventing transfusions, reducing fatigue, and lowering the number of defective blood cells.
The data suggest Novartis’ drug “could be practice-changing for PNH and could essentially allow patients to live a normal life with just one pill each morning and night,” said Régis Peffault de Latour, a hematologist at Université Paris Cité who presented the results at ASH.
Novartis expects to file iptacopan for global approvals next year, submitting data from the head-to-head Phase 3 and a second, single-arm study in which the drug met its primary. | Costly tests and burdensome blood thinners had no effect on preventing miscarriage In a challenge to common medical practice, a large study found that administering blood thinners to women at risk for blood clots had no effect on the rate of miscarriage, according to the first international, randomized study of its kind.
For years, doctors have prescribed daily self-injections of blood thinners to women with thrombophilia, an inherited clotting disorder, who had experienced miscarriage in the past, a practice based largely on observational studies suggesting a correlation between the two.
To test that notion, researchers in the U.S. and Europe enrolled more than 400 women with thrombophilia and a history of miscarriage who were trying to conceive, randomizing them to receive either standard pregnancy care or daily doses of blood thinners. In the end, the rates of live birth were nearly identical: 71.6% in the blood thinner group compared with 70.9% in the standard-care group. Adverse events, including bleeding and low platelet counts, were significantly higher among those taking blood thinners: 44% versus 27%.
The data suggest that testing for thrombophilia, which is costly, and self-injecting blood thinners, which is burdensome, might be unnecessary for women with a history of miscarriage, said Saskia Middeldorp, head of internal medicine at the Netherlands’ Radboud University Medical Center, who presented the results at ASH. | Farewell from New Orleans! That’s it from us! If you still haven’t had enough or want to learn more about some of the key research coming out of ASH this year, join us tomorrow for the ASH Recap. Damian Garde will be speaking with Michael Sekeres on work that challenged the dogma in hematology, and Angus Chen will talk with Laura Michaelis on practice-changing research this year. Register for the virtual event here.
Hope you all have a safe trip home! | | | |
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