On Jan. 17, the Food and Drug Administration (FDA) granted traditional approval to treatment with Calquence (acalabrutinib) plus bendamustine and Rituxan (rituximab) for patients with previously untreated mantle cell lymphoma (MCL) who are ineligible for autologous hematopoietic stem cell transplantation (HSCT), according to a news release from AstraZeneca. Importantly, Calquence is now the first and only Bruton tyrosine kinase (BTK) inhibitor approved for the first-line treatment of MCL in the country.
How This Brings a New Option Earlier In The Treatment Paradigm
BTK inhibitors, such as Calquence, work by targeting and blocking the BTK-specific protein, sending out growth and survival signals instead, according to calquence.com. Because MCL is a rare and typically aggressive form of non-Hodgkin lymphoma (NHL), which is often diagnosed at an advanced stage, it is vital that this new treatment approach will target the cancer earlier in the therapeutic process. MCL, which affects the body’s B-cells, may benefit from the targeted treatment approach of Calquence, as it directly targets how cancer cells grow, divide, and spread.
“[The FDA approval] provides another option for this patient population,” Dr. Tycel Phillips, an expert in the MCL treatment space, stated on the importance of the FDA approval in an exclusive interview with CURE®. “Given the [common] knowledge of these two drugs with the physician and in the community space, it allows a bit easier of an uptake to [providing this treatment] in this setting."
Phillips currently serves as an Associate Professor in the Division of Lymphoma, Department of Hematology and Hematopoietic Cell Transplantation, at City of Hope in Duarte, California.
As the first BTK inhibitor approved for the front line MCL treatment, this is a much-needed advancement as patients can have severe symptoms at the time of diagnosis, according to the news release, making the early use of an effective therapy which can improve outcomes for patients vital.
“In this patient population, there weren't a ton of options," Phillips explained, saying, “The fact that this combination had progression-free survival [PFS] benefit, meaning the disease state of remission was undetectable longer with the experimental combination versus the standard of care, positions [the treatment] very well in this space.”
More on the FDA Approval
The January regulatory approval of the Calquence combination came following a data read-out of the ECHO trial, according to the FDA website. The randomized, double-blind, placebo-controlled, multicenter study evaluated the efficacy of the treatment combination in 598 patients with MCL who were at least 65 years of age and were not eligible for HSCT. Eligible trial participants were treated with Calquence plus bendamustine and Rituxan or placebo plus bendamustine and Rituxan.
At a median follow-up of 49.8 months, the PFS was statistically significantly longer for patients treated with the Calquence combination, with a median PFS of 66.4 months versus 49.6 months in the investigative versus placebo combination arms, respectively.
“This was a study looking at patients who were considered to be transplanted ineligible. At the time of onset, these were patients 65 [years of age] and older with newly diagnosed MCL, so these patients could not have received any treatment prior for their disease,” Phillips continued. “The key takeaway is that it did meet the primary end point, [meaning] there was a PFS benefit with Calquence plus bendamustine and Rituxan over bendamustine and Rituxan. There was no overall survival [OS], though there was a trend toward OS, but it did not meet statistical significance in this patient population.”
Regarding safety, the news release stated that the safety and tolerability of Calquence treatment was consistent with its previously known safety profile, and no new safety signals were identified. It was noted on the FDA website that serious side effects occurred in 69% of patients who received the Calquence combination, and fatal side effects occurred in 12%. Serious effects reported include pneumonia, COVID-19, pyrexia, second primary malignancy, rash, febrile neutropenia, atrial fibrillation, sepsis and anemia.
Phillips said that, "A key point, unlike what we saw with the SHINE [trial] — was that there was no unexpected deaths, unexplained or increase in toxicities in the experimental arm, so safety was not a concern with this combination, which was what likely doomed the SHINE study.”
SHINE is a phase 3 clinical trial which investigated the addition of Imbruvica (ibrutinib) to bendamustine and Rituxan treatment in older patients with newly diagnosed MCL. Although this trial showed favorable outcomes, there was a significant increase in grade 3/4 toxicity, according to information published in “The New England Journal of Medicine”.
Phillips ended his conversation with CURE by imparting a message of hope for patients with MCL. He said, “My key takeaway is optimism. There are more and more treatments being approved for MCL, and the more treatments that are being approved in this patient space, the longer patients will generally be expected to live with [their] cancer. Hopefully, this gets us closer to one day saying that we have a cure for [MCL], which is our ultimate goal.”
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