When R-CHOP Might Not Be Enough
- Most people with diffuse large B-cell lymphoma start out with a drug combination called R-CHOP
- People with certain genetic mutations may need more aggressive treatment
- One of the regimens used to treat these cancers is called R-EPOCH, which includes one additional chemotherapy drug
But for a small subset of people with double-hit and triple-hit lymphomas, that regimen may not be enough to control the cancer. In these patients, either two (double-hit) or three (triple-hit) genes have swapped places on the chromosome. These mutations make the cancer more aggressive and harder to treat.
Read MoreAlternatives to R-CHOP
In people with the more aggressive double- and triple-hit lymphomas, doctors may switch to a more aggressive treatment approach. One of these regimens is called dose adjusted R-EPOCH. It adds one more chemotherapy drug to R-CHOP — etoposide. R-EPOCH is given as an infusion over a four-day period. “It often requires a hospital stay or an infusion pump. It’s a more cumbersome regimen than R-CHOP,” Dr. Friedberg says.Adding another drug potentially increases the number of side effects people on this treatment develop. And, because doctors gradually raise the dose with each cycle, eventually everyone who is on this treatment will reach the point where they experience some toxicity.
Although he says there aren’t good randomized studies showing that R-EPOCH is better than R-CHOP, many doctors feel that it is a better strategy. A new clinical trial plans to investigate whether R-EPOCH truly offers an advantage.
Other intensive drug combinations have also been studied for double- and triple-hit lymphomas, including hyper-CVAD — a combination of the chemotherapy drugs cyclophosphamide, vincristine sulfate, and doxorubicin, plus the steroid dexamethasone, along with methotrexate and cytarabine. The “hyper” stands for hyperfractionated. The drugs are given in smaller but more frequent doses.
There might also be a role for high-dose chemotherapy and autologous stem cells transplant in the treatment of double- and triple-hit lymphomas, although it “does not appear to have a significant role, particularly after R-EPOCH,” Dr. Friedberg says.
Another promising approach is CAR T-cell therapy. This treatment, which re-engineers immune cells to help them find and attack the cancer more effectively, is already approved for people whose lymphoma has relapsed. “There’s some enthusiasm to potentially look at CAR T-cells earlier in the course of the disease in people with high-risk disease,” Dr. Friedberg says.
Future research studies will hopefully shed light on the reasons why double- and triple-hit lymphomas are more resistant to standard treatments, and identify which therapies might be more effective against these cancers.
Learning Your Genetic Status
Large cancer centers like the Wilmot Cancer Institute routinely perform genetic tests on each patient who is diagnosed with lymphoma. However, that may not be the case at smaller or rural hospitals. “There are probably many patients who don’t know their tumor is double-hit,” Dr. Friedberg tells SurvivorNet.
One of the most important steps in any lymphoma journey is to get an accurate diagnosis, he says. For that to happen, a specialist called a hematopathologist needs to review a sample of the cancer removed during a biopsy to determine its genetic status.
Dr. Friedberg stresses that being diagnosed with a double- or triple-hit lymphoma does not always portend a dire outlook. “There are subsets of patients who do very well, and are cured,” he says. “R-CHOP does do relatively worse in this type of cancer, but it doesn’t mean that this is a death sentence.”
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