For people whose lymphoma has recurred, there were encouraging findings about a new drug combination featured at the American Association for Cancer Research’s annual meeting. Matthew Matasar, a Memorial Sloan Kettering medical oncologist and hematologist, presented the trial results of a new treatment for indolent B cell lymphoma. The study was also published online in The Lancet Oncology.
Dr. Matasar, who is Regional Care Network Medical Site Director at MSK Bergen, discussed the promising study.
Several other researchers from MSK also presented at the 2021 AACR Annual Meeting.
What does this study mean for patients?
We found it can be effective to add another drug to the standard therapy for people whose lymphoma has returned after other treatments. We learned that this new drug combination is safe and extends the time the disease is controlled by more than 50% — from 13.8 months to 21.5 months.
It’s too soon to know whether this drug combination improves overall survival because patients with these types of lymphoma live a long time. But I expect this to become an available standard treatment for patients.
What drugs were studied in the trial?
The first drug was rituximab (Rituxan®), which is a monoclonal antibody that’s used to treat many types of cancer and also some autoimmune diseases. The second drug is called copanlisib (AliqopaTM). It’s a newer targeted therapy that’s currently approved to treat follicular lymphoma. It targets a pathway called PI3K, which is involved in many cancers.
Both drugs are given through IV infusion, but neither of them is chemotherapy.
What kind of lymphoma was included in this study?
All of the patients had indolent B cell lymphomas that had returned after other treatments. Indolent lymphomas are slow-growing types of blood cancer. They can affect both men and women of any age, but they’re more common in older adults. We have a lot of treatments for these diseases, and each of them works well for a while. But the diseases are usually not curable, and every time one comes back, it’s harder to treat.
Because these cancers happen more frequently in older people who may have other illnesses or health problems, there’s an especially great need to find more treatments that are effective but don’t have the side effects of chemotherapy.
This study included patients with four subtypes of lymphoma — follicular lymphoma, marginal zone lymphoma, small lymphocytic lymphoma, and lymphoplasmacytic lymphoma, which is sometimes known as Waldenström macroglobulinemia. We saw improvements in all of these subtypes.
How was the trial conducted?
This study, called CHRONOS-3, was a randomized, controlled phase III trial. It was a global effort, with investigators and patients participating from all over the world.
In the study, 307 patients received rituximab and copanlisib, and 151 received rituximab and a placebo. The patients have so far been followed for an average of 19.2 months. Our analysis so far shows there was a 48% reduction in the risk of disease progression or death in patients who got the drug combination.
What side effects did the patients have?
The side effects of using these drugs separately were already well known. Rituximab can suppress the immune system and make people more likely to get infections. The side effects of copanlisib include high blood pressure and high blood sugar, related to the drug’s effect on the PI3K pathway.
Thankfully, the results of this trial showed no unexpected safety concerns from combining the drugs. One thing we were concerned about was organ inflammation, but only 6% of patients had inflammation of the lungs and that inflammation was severe in only 2% of cases.
What are the next steps for this treatment?
In the short term, I believe this study establishes that the combination of rituximab and copanlisib is a safe and effective treatment for patients with relapsed indolent B cell lymphoma.
The more important long-term impact is that for the first time we have the ability to combine a drug that targets the PI3K pathway with other medicines without leading to unacceptably high complications and risks. This paves the way forward for studying copanlisib in other combinations, including with chemotherapy, immunotherapy, and other targeted drugs. We are continuing to work toward developing treatments that maximize effectiveness and minimize risks.
