A 76-Year-Old Woman With High Risk Mantle Cell Lymphoma - Episode 4
Kami Maddocks, MD: The NCCN [National Comprehensive Cancer Network] Guidelines for relapsed/refractory mantle cell lymphoma divide the approach in looking at how good of a remission patients got with their initial therapy. If patients got what they identify as a good remission with their initial therapy, the median PFS, progression-free survival, is expected with that therapy, then they list more options than a patient who had a poor response or a poor remission duration to their initial therapy.
In the patients who relapsed earlier or have a poor remission, they really recommend approach with 1 of the targeted therapies and not reusing chemotherapy. There are several targeted therapies, including 3 oral BTK inhibitors approved: ibrutinib, acalabrutinib, and most recently zanubrutinib was approved in November 2019 for relapsed/refractory mantle cell lymphoma.
Rituximab and lenalidomide, which is an oral immunomodulatory agent; rituximab; and a proteasome inhibitor, bortezomib. Also listed in the NCCN Guidelines is venetoclax, which is an oral BCL2 inhibitor with high response rates in progression-free survival, similar to the BTK inhibitors. Although this is in the guidelines, it is not FDA approved at this time as a treatment for mantle cell lymphoma.
For a patient who achieved prolonged remission durations to their initial therapy, for any chemotherapy approach, it is recommended to repeat chemotherapy depending on the initial treatment. If somebody has received R-CHOP [rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, prednisone] or a more aggressive and intensive regimen, bendamustine-rituximab is a reasonable option if they achieved a prolonged remission duration with that therapy. The same is true for using R-CHOP [rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, prednisone] in a patient who has received previous bendamustine-rituximab. Again, all those oral nonchemotherapy approaches, with those targeted agents, are also listed in the NCCN Guidelines for patients with prolonged remission duration.
When trying to decide second-line treatment for our patient, currently I think an oral BTK inhibitor is an appropriate approach to any patient. They have high overall response rates, they have reasonable complete remissions, and they have good progression-free survival. It’s most especially good when it’s used as the initial therapy at first relapse. In the majority of patients my choice is going to be an oral BTK inhibitor regardless of remission duration.
Although I will say that these therapies at this time, once they’re started, are continued if a patient is tolerating and responding, so they are somewhat indefinite in that situation. There is a handful of patients who have had a prolonged remission duration to chemotherapy, where I’m looking at not wanting them to have to be on a therapy forever. Or if cough is an issue, then maybe the patient who also had to repeat a less intensive chemotherapy approach there. But for a large number of patients a single-agent BTK inhibitor, or a trial with a BTK inhibitor in combination, is the preferred treatment of choice.
Transcript edited for clarity.
Case: A 76-Year-Old Woman with High Risk Mantle Cell Lymphoma