“dramatically” changing the way CLL is treated, says Greenberger, potentially leaving chemotherapy behind for some patients. At ASH, investigators will detail ibrutinib’s clear superiority over the standard of care for patients 65 and older; its superiority, with the drug rituximab (Rituxan), over chemotherapy plus rituximab for previously untreated younger patients, which has “immediate practice-changing implications,” according to the study authors; and its increased power in combination with another approved CLL drug, venetoclax (Venclexta).
Ibrutinib targets the protein Bruton’s tyrosine kinase (BTK), which plays a key role in the expansion of CLL. “Imbruvica, in its various regimens and combinations, has won every time, and the only risk it faces is the host of other BTK inhibitors coming over the horizon with slightly different safety and tolerability profiles,” Leerink analyst Geoffrey Porges wrote in a note to investors last week.
Over time, CAR-T could become a factor in CLL, especially for people who aren’t helped by ibrutinib or venetoclax; results at ASH are from early CLL trials at the Fred Hutchinson Cancer Research Center, City of Hope (using Juno Therapeutics’ experimental JCAR017), and at Memorial Sloan Kettering Cancer Center.
For acute myeloid leukemia (AML), we’ll highlight a few studies. The first isn’t technically AML, it’s the rare blood disorder myelodysplastic syndrome, or MDS, in which mutations arise in the patient’s blood stem cells. It can be a precursor to AML, with about 30 percent of MDS patients converting, typically those whose cells have a higher number of mutations. (AML is a tough cancer to treat because of its wide range of genetic subtypes.)
But MDS can be deadly without converting to AML, leading to severe, even deadly anemia. Partners Celgene (NASDAQ: [[ticker:CELG]]) and Acceleron Pharmaceuticals (NASDAQ: [[ticker:XLRN]]) have brought the drug luspatercept—also in development for beta-thalassemia—through Phase 3 for MDS, with results that indicate the drug can significantly reduce the number of blood transfusions that MDS patients require to avoid anemia. Celgene and Acceleron will discuss the details of that study, MEDALIST, at ASH.
There are also promising data for newly diagnosed AML patients who aren’t eligible for chemotherapy, and a multi-arm trial, sponsored by the Leukemia & Lymphoma Society, which assigns patients with various genotypes to different arms and get them on treatment within seven days.
For the roughly 20 percent of AML patients with IDH mutations, two drugs from Agios Therapeutics (NASDAQ: [[ticker:AGIO]]) will produce updates at ASH. Ivosidenib (Tibsovo) alone has promise in previously untreated IDH1-mutation patients, based on interim Phase 1 data;
and, when combined with chemotherapy, ivosidenib and enasidenib (Idhifa, for IDH2 mutations) have shown enough in newly diagnosed patients to warrant moving into Phase 3, according to investigators.
Acute lymphoblastic leukemia, or ALL, is a rare leukemia, with less than 6,000 estimated new U.S. cases in 2018. But it’s a nasty disease and a difficult proving ground for new therapies. The first-ever CAR-T approval was for kids and young adults with ALL based on data that showed that 36 percent of patients who initially did well relapsed after 12 months. (These are patients who had already failed to respond to many other treatments, including bone marrow transplant.)
Another CAR-T, from Juno Therapeutics, was pulled from ALL trials after several patients died during the course of treatment. Juno, now owned by Celgene, is now working on pediatric ALL with a different experimental CAR-T product (no ASH update, however), and Gilead’s Kite division hopes that updated Phase 1 data at ASH builds momentum for its Yescarta to gain approval in ALL.
Efforts to broaden the attack on ALL by hitting the cancer from two directions are advancing as well. The first generation of CAR-Ts all go after the common protein CD19; at least three groups are reporting progress at ASH—here, here, and here—in going after a second protein, CD22, also often present on ALL cells.
Meanwhile, researchers at the University of Pennsylvania are working on CAR-T plus a checkpoint inhibitor.
All of those CAR-T programs require engineering a patient’s own cells, a complicated and expensive proposition. Another technique, using “off the shelf” cells, could prove cheaper and more straightforward, but it’s not as far along in development. Updated Phase 1 data for the most advanced of these treatments, called UCART19 and developed by Allogene Therapeutics (NASDAQ: [[ticker:ALLO]]) and Servier, will be discussed at ASH.
It’s not all CAR-T all the time for ALL, to be sure. Amgen (NASDAQ: [[ticker:AMGN]]) first received approval to treat one genetic type of ALL with its antibody drug blinantumumab (Blincyto) in 2014 and has since been cleared to treat a broader group of patients.
At ASH, European investigators will discuss the survival rates of adults receiving blinatumumab, and clinicians in the U.S. will step through a Phase 1 study of the drug combined with two checkpoint inhibitors.
BETA-THALASSEMIA
Next year is shaping up as a big one for patients with beta-thalassemia, a rare, crippling blood disease that affects about 15,000 people in the U.S. and Europe. Two new medicines could be approved, and both would upend current treatments.
“It’s very exciting,” says Craig Butler, the executive director of the nonprofit Cooley’s Anemia Foundation. (Cooley’s is another name for beta-thalassemia.)
Patients with beta-thalassemia have inherited a faulty gene that codes for hemoglobin, the protein in red blood cells that carries oxygen. The effects depend upon the amount of normal hemoglobin the body manages to produce. Patients with “mild” thalassemia might not need help at all. The more severe beta-thalassemia major is potentially deadly because of severe anemia that requires a lifetime of blood transfusions, often every two to four weeks. Repeated transfusions have their own risk: a dangerous buildup of iron that, in turn, requires iron chelation therapy to prevent organ damage, heart failure, or death. (Bone marrow transplants are a potential cure, but they’re not available to everyone and carry their own risks as well.)
Transfusions and iron chelation can help people with beta-thalassemia major live until their 50s or beyond, Butler says. But there is room for improvement for patient health and for reducing healthcare costs. Transfusions are all-day affairs; patients frequently miss school or work. It’s hard to tell which iron chelation drugs will work for each patient. And the cost is daunting: a study in the 2017 journal Blood estimated the average cost at $75,000 per patient, per year. Butler estimates it typically costs the system $200,000 to $300,000 per person, per year, for all the associated costs.
Therapies with key updates at ASH could
