Academic Focus: CAR-T Therapy for Relapsed/Refractory NHL - Episode 1
Matthew Lunning, DO: You have to begin with diffused large B-cell lymphoma at its diagnosis. We treat diffused large B-cell lymphoma, in the majority of cases, with curative intent, which means that the goal of the initial line of therapy is to take this lymphoma away and never have it come back.
In 2018 we continue to use an R [rituximab]-chemotherapy—based induction strategy for those who can get curative intent therapy. R-CHOP is, I believe, the standard of care that has been challenged in multiple clinical trials in a randomized fashion. At least in the United States, this continues to be the frontline therapy. In those patients who have advanced stage disease who get 6 cycles of R-CHOP, there is about a 50% chance that we have a long-term disease-free survival complete solubility.
The other 50% is what we’re talking about here today from the relapsed/refractory—diffused large B-cell lymphoma standpoint. When this occurs, with a severe relapse that shows on a biopsy, the first question that you have to ask yourself is: “Could I potentially transplant this patient?” If the answer is yes and they fall into the transplant-eligible category, then the standard of care is second-line, high-intensity therapy with the intent to consolidate with high-dose therapy and autologous stem-cell rescue/transplant.
Now, in those patients who are transplant ineligible, the goals of care changes to focus more on disease control and quality of life as a premium. In that case we may change the intensity of our therapies or choose different options than we would in intensive therapy of transplant-eligible arm.
Speaking to directly the transplant-eligible arm, second-line therapies like RICE [rituximab, ifosfamide, carboplatin, etoposide phosphate], DHAP [dexamethasone, high-dose Ara C (cytarabine), cisplatin], or GDP [gemcitabine, dexamethasone, cisplatin] with or without rituximab-containing regiments—depending upon whether they were coming off R-CHOP chemotherapy and were refractory to frontline therapy or experienced a sizeable remission duration—those response rate are well within the 60% range. It’s important that there’re data to show the potential of PET-negative remission at that point, which may help with long-term improvement post autologous transplant. Those people in a partial remission need to be analyzed for the exact extent of their remission. Depending on these data, you would want to consider radiation after transplants if it’s a localized, focused area versus other options, to try and get a third therapy to potentially improve their remissions prior to transplantation.
The transplant-eligible demographic would use RICE, R-DHAP [rituximab + dexamethasone, high-dose Ara C (cytarabine), cisplatin], or RGDP [rituximab, gemcitabine, dexamethasone, cisplatin], all of which have been extensively studied. In the CORAL study the R-DHAP versus R-I [rituximab, ifosfamide] study was performed to show equivalence. Additionally, the Canadian Study, RGDP versus R-DHAP, showed equivalences as well. You can’t compare RICE to R-GDP, but you could argue that all 3 of those chemotherapy regimens are equivalent in the second-line setting.
It is important that those patients who achieve good remission prior to going into a high-dose autologous stem-cell rescue therapy, or auto transplant, maintain long-term disease control or perhaps yield complete cure. Unfortunately, about half of those patients will not achieve a long-term disease-free state.
I should also mention that there is a population that is at higher risk when their disease recurs: people who have relapsed very quickly or those individuals who never have a disease remission at all. That’s a category that, when we’re thinking about taking them through second-line therapy, have to make sure they’re truly responding to second-line therapy. If not, they probably should not receive a consolidated transplant.
Transcript Edited for Clarity