Kami J. Maddocks, MD, talks CAR T-cell therapy approvals for the treatment of relapsed/refractory diffuse large B-cell lymphoma and follicular lymphoma plus a new treatment supplanting R-CHOP.
There were 2 big breakthroughs in the treatment of lymphoma this past year. One is ready for treatment and hopefully will be ready to bring to patients. [There were] 2 randomized trials [NCT03391466; NCT03575351] looking at the use of chimeric antigen receptor T-cell, or CAR T-cell, therapy in the second-line setting for patients with diffuse large B-cell lymphoma [DLBCL] who either don’t respond to initial therapy or relapse within 1 year of receiving their initial treatment. [These trials] showed a benefit to CAR T-cell therapy in the second-line setting vs our previous standard treatment, which was further chemoimmunotherapy followed by autologous stem cell transplant. So, now there are FDA-approved indications for 2 products, and this has had the biggest impact on patient care.
The second exciting thing was that we saw, for the first time, a positive trial in front-line DLBCL [NCT03274492]. We saw phase 3 trial results evaluating R-CHOP [rituximab (Rituxan) plus cyclophosphamide, doxorubicin, vincristine, and prednisone] vs R-CHP [rituximab (Rituxan) plus cyclophosphamide, doxorubicin, and prednisone] plus polatuzumab [Polivy]. This trial was positive in that it showed a 2-year progression-free survival [PFS] advantage to using polatuzumab in the front-line setting. That’s not yet been FDA approved, but just the results of that trial and the hope that [this new potential treatment] will be available in the future is the second exciting update.
[As for] CAR T-cell therapy in the second-line setting, this has [probably provided] the biggest benefit [to patients]. While it’s a smaller population of patients who are refractory, you do see patients that relapse within a year of completing therapy, and the ability to give them this CAR T-cell therapy earlier [improves outcomes] compared with further chemoimmunotherapy, which frequently doesn’t work. We’ve also seen the approval of a second CAR T-cell product for relapsed/refractory follicular [lymphoma; NCT03568461]. CAR T-cell therapy has also been effective for mantle cell lymphoma in the relapsed/refractory setting and, while that’s not necessarily a new approval, we’ve seen updated results for patients from the original phase 2 trial. CAR T-cell therapy across diseases has had one of the biggest impacts in our patient population.