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Sickle cell community reacts to FDA approvals, advocating for equity in multiple myeloma, and more

December 10, 2023

Hello again. This is Jonathan Wosen, Angus Chen, and Meghana Keshavan with a guest spotlight on a patient for today's newsletter. Here are some highlights from the second day of ASH, which kicked off with the 10th annual ASH Foundation run/walk. Fun fact — participants passed what appeared to be the largest ketch in the world — the superyacht Aquijo docked here in San Diego. Check back in tomorrow for our last newsletter of the meeting!

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sickle cell

Sickle cell experts cautiously optimistic after historic FDA approvals

The timing of ASH couldn't have been better for sickle cell experts, with the meeting kicking off a day after the Food and Drug Administration's historic approval of two gene therapies for the devastating disease. Their reaction to the moment can be best summed up in two words: measured optimism.

Doctors and researchers celebrated the advent of cutting-edge therapies for a disease that has long gone ignored and underfunded. But they also called for perspective, noting that these new drugs are pricey, complex to administer, and won't immediately be accessible to everyone who needs them.

"From a clinician, from a scientist's perspective, I think that it's just groundbreaking. Medicine has changed forever," said Akshay Sharma, a physician who treats children with sickle cell at St. Jude Children's Research Hospital. "Is this really going to transform the care for patients with sickle cell disease in the next five years? I remain skeptical."

The price tags of these therapies have been a constant talking point during the meeting, as has the gap between them. Vertex Pharmaceuticals and CRISPR Therapeutics have priced their drug, Casgevy, at $2.2 million, while Bluebird Bio has set the price for Lyfgenia at $3.1 million. And while the therapies use different approaches, CRISPR/Cas9 gene editing for Casgevy and viral gene delivery for Lyfgenia, experts were baffled by how much more Bluebird's drug costs. They also wondered whether the novelty of these therapies was distracting everyone from an existing (and less expensive) approach that can cure patients: bone marrow transplants.

No one was surprised by the approvals given that clinical trials show both drugs help prevent the debilitating pain crises seen in patients with severe disease. The question is no longer whether these drugs work, experts say, but instead how to get them to patients.

Read more.


Multiple myeloma

Advocating for equity in multiple myeloma

For two years, Oya Gilbert was shuffled from "ologist" to "ologist," who deemed his episodes of extreme fatigue, body pain, and shortness of breath as hypochondria — or opioid abuse. They were wrong. It was multiple myeloma, the most common blood cancer among Black Americans. But since Gilbert lives in rural, predominantly white Waynesboro, Penn., physicians simply weren't clued into the signs of his increasingly debilitating disease: "I don't think my doctors understood the nuances of treating African Americans," he said.

Six years ago, Gilbert was finally diagnosed correctly, and began a journey to better understand his disease — and why there was such a lag in his diagnosis. He is now working with the International Myeloma Foundation to find ways to spread awareness about the disease in underserved communities, using technology to bridge the geographical and educational gaps he's faced. He's here at ASH to learn, and to advocate for his community.

"I still don't have access to the best therapies, but through my work with the IMF, I am learning that they do exist," Gilbert said. "I've never been offered access to a clinical trial, through my whole journey. And I've never been in remission." 

One in five patients with multiple myeloma is Black, yet they account for only 4% of clinical trial participants in this space.

"There's a delay or an inherent bias in not referring these patients to transplant centers," said Saad Usmani, a myeloma specialist at Memorial Sloan Kettering, who spoke on a panel at ASH about racial disparities in cancer care. "But if they get transplants, minority patients did better than white populations."

Treatments like CAR-T and bispecifics are being highlighted here at ASH, but the reality is that they continue to be out of reach for most patients. Gilbert's aim with the IMF, and here at ASH, is to help move that needle. 

"To me, education about this disease is just as important as the treatments themselves," he said. "It empowers us to make the right decisions for ourselves."


leukemia

Minimal residual disease guides duration of treatment in CLL

Using a combination of the targeted therapies ibrutinib and venetoclax is becoming standard of care in previously untreated chronic lymphocytic leukemia, but one question that has remained is how long patients should be on treatment. In some patients, longer treatment may increase the chances of a cure, but it can also raise the risk of the cancer evolving resistance to the drugs. Peter Hillmen from the Leeds Institute of Medical Research presented data at ASH today that suggest clinicians could tailor that duration of treatment to how quickly the patient responds to the drug combination by measuring minimal residual disease.

Hillmen ran a randomized study comparing patients on chemotherapies fludarabine and cyclophosphamide plus rituximab versus patients on ibrutinib plus venetoclax. In the ibrutinib and venetoclax arm, Hillmen measured how quickly patients became MRD negative to guide how long they would be on the drugs. If patients became MRD negative after one year, for example, they would receive venetoclax and ibrutinib for two years, and MRD negativity after two years would mean treatment for four years. He found this method showed 97.2% progression-free survival at three years compared to 76.8% PFS in the chemotherapy and rituximab arm.

"For CLL, duration of therapy can be very long and associated potentially with resistance," Hillmen said. This study, he added, is "about how we give time limited therapy or try to cure patients with the combination we have. Now we have therapies that really do probably stop people from dying or even cure them."



car-t

Study: Some patients waiting for CAR-T benefit more from an infusion of their own blood stem cells

CAR-T cell therapy can be transformative for cancer patients, but those in need of these treatments sometimes have to wait months to get them, forcing doctors to use other therapies in the meantime to keep their disease at bay. Sometimes, these so-called bridging therapies can send patients into complete remission, with no trace of cancer detectable by medical imaging. New research presented at ASH suggests that, in these cases, an infusion of a patient's own blood stem cells may work better than the CAR-T therapy they'd been waiting to receive.

The analysis, presented during a morning press briefing, was based on looking back on data from 2018 to 2021 from 360 patients with large B-cell lymphoma (LBCL) who had relapsed after first-line therapy but who went into complete remission while on bridging therapy. Patients who went on to receive CAR-T had a 48% relapse rate two years later compared to 28% among those who were infused with their own blood stem cells. CAR-T recipients also had a higher rate of disease worsening, with a progression-free survival rate of 48% compared to 66% for patients given a blood stem cell transplant. Those results were reinforced when researchers crunched the numbers in a way that accounted for a variety of clinical variables.

The results aren't a knock on CAR-T, cautioned Mazyar Shadman, an oncologist at the University of Washington and the study's lead author, adding that clinical trials have proven that CAR-T therapy should be the standard of care among relapsed patients with LBCL. Instead, this study offers data that can inform the treatment of a subset of these patients: those who show complete response to bridging treatment. And if a blood stem cell transplant fails in these cases, Shadman adds CAR-T can still be an effective back-up option.

"We should do our best to get patients to CAR-T therapy as soon as possible," he said. "But in the meantime, this is  data that in some situations could be helpful in decision making."


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Thanks for reading! Until tomorrow - Jonathan & Angus

Jonathan Wosen is STAT's West Coast biotech & life sciences reporter, based in his hometown of San Diego. Jonathan holds a doctorate in immunology from Stanford and a master's in science communication from the University of California, Santa Cruz. Yes, that is a lot of school. In his spare time, he enjoys jogging and following all things NBA-related.

Angus Chen is a cancer reporter at STAT. Before journalism, Angus was a geology research grunt where his primary job was smashing rocks with a very large hammer. He lives in Oakland, Calif., and enjoys surfing at gnarly Ocean Beach, San Francisco.


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