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Led by Dr. Roger G. Owen, St. James’ University Hospital, Leeds, UK, and colleagues recently concluded that for those patients with treatment-naïve or relapsed/refractory  a type of non-Hodgkin lymphoma, single-agent acalabrutinib is safe and active. Dr. Owen pointed out that although the standard of care with WM is chemoimmunotherapy, the infectious and hematologic toxic impact can be too great. Controversy attached to the drug as the commercial sponsor falsified some data in the past.

What is Waldrenstrom macroglobulinemia (WM)?

乐动体育 is a rare cancer with only about 1,500 cases in America per year. It affects two types of B cells: lymphoplasmacytic cells and plasma cells. Both cell types are white blood cell types. WM is characterized by having high levels of a circulating antibody known as immunoglobulin M (IgM), which is made and secreted by the cells involved in the disease. WM is an “indolent lymphoma” (it tends to grow and spread slowly) and a type of lymphoproliferative disease which shares clinical characteristics with the indolent non-Hodgkin lymphomas. It occurs more frequently in older adults. It is incurable but treatable.

What is Acalabrutinib?

With a trade name of , it is a medication used to treat a type of non-Hodgkin lymphoma known as mantle cell lymphoma. It is specifically used for patients who had previously been treated with another therapy. It is unclear if it results in improved outcomes as of 2019, according to . A second-generation Bruton’s tyrosine kinase inhibitor, an important therapeutic class represents a paradigm-changing advance in precision oncology. Approved for medical use in America in , the wholesale cost in the U.S. is $14,064 . Developed by , Anglo/Swedish AstraZeneca acquired a 55% stake in the company for $4 billion in 2015 with an option to acquire the remaining 45% stake for $3 billion more—conditional on first approval in both the U.S. and Europe and the establishment of .

The Controversy

AstraZeneca bought a majority stake in Acerta, a blood cancer biotech for $4 billion. Back in 2017, it was reported that Acerta acknowledged some of the early data concerning the drug acalabrutinib was . While AZ invested in this promising burton tyrosine kinase (BTK) inhibitor—and the drug was being tested in multiple clinical trials for blood cancers (e.g., CLL, mantle cell lymphoma) it is similar in class to AbbVie and Johnson & Johnson’s Imbruvica. However, Acerta had to retract an abstract, published in medical journal Cancer Research two years ago—right before an AstraZeneca cash injection—the data showed the drug as effective in treating solid tumors in mice reported Fiercebiotech.

Apparently, a former Acerta employee, the culprit, acted alone. And AstraZeneca stated this fact had “no impact on the integrity of acalabrutinib data in any clinical trials, and there was no risk to patient health.” 

TrialSite New乐动体育 observes these incidents occur more often than anyone would like. They are typically blamed on a rogue employee(s), but we have a saying—“the fish often can stink from the head.” Often some of these companies generate so much pressure on their employees to produce nearly impossible results that the employs, or the weak-willed and value-challenged ones, succumb to fear, uncertainty, and doubt and take actions to improve outcomes. This is why transparency is so unbelievably important. Health and powerful drugs are a national interest for any nation. The health consumers of that nation demand to understand what has gone into a drug, what has transpired to produce the drug, and what are the true risks associated with the drug.

The Study

乐动体育Dr. Owen and a team from St. James University Hospital evaluated the activity and safety of acalabrutinib in patients with WM in a single-arm, multi-center, Phase II trial. Eligible patients were 18 or over, treatment-naïve or had relapsed/refractory disease with no prior BTK inhibitor therapy and an Eastern Cooperative Oncology Group performance status of ≤2.  appears to be sponsored by Acerta Pharma BV. As reported, they treated 106 patients (14 treatment naïve and 92 relapsed/refractory) were selected for study inclusion. As reported by Janelle Bradley of Oncology Learning Network, the primary endpoint of the trial was an investigator-assessed overall response (OR) based on the 6th International Workshop for Waldrenstrom macroglobulinemia (IWWM) and the modified 3rd IWWM workshop criteria. The OR rate and safety were assessed in all patients who received ≥1 of the study drug.

乐动体育The drug was administered twice a day in 28-day cycles until profession or unacceptable toxicity occurred.

Results

As reported by Ms. Bradley, with a median follow-up of 27.4 months, 93% of the 14 treatment-naïve patients and 93% of the relapsed/refractory patients achieved an OR. Treatment discontinuation occurred in 50% and 25% of the patients, respectively. Documented adverse events (grade 3-4) were neutropenia (16%), pneumonia (7%), atrial fibrillation(1%), and bleeding (3%). Common serious AEs included lower respiratory tract infection (7%), pneumonia (7%), pyrexia (4%), cellulitis (3%), falls (3%), and sepsis (3%).

乐动体育Treatment-related cases of pneumonia were 5% and lower respiratory infection (4%)—1 death was reported, which occurred from an .

Investigator Comment

Dr. Owen and colleagues concluded, “This study provides evidence that acalabrutinib is active as a single-agent therapy with a manageable safety profile in patients with treatment-naïve or relapsed or refractory WM.” They rightly noted, “Further studies are needed to establish its efficacy against current standard treatments and to investigate whether outcomes can be improved with combination therapies. This means, frankly, that more studies need to be done to determine A) the true efficacy of this treatment B) whether better outcomes (e.g., factoring in safety) can be had using combined therapies.

Lead Investigator/Researcher

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