Autologous transplant improves survival vs. CAR-T for certain patients with lymphoma
Click Here to Manage Email Alerts
Key takeaways:
- Auto-HCT linked to improved PFS and reduced relapse rate for patients achieving a complete remission.
- Researchers noted no significant difference in 2-year OS rates between treatment types.
SAN DIEGO — Patients with relapsed large B-cell lymphoma who achieved a complete remission had a reduced relapse rate and improved PFS with autologous transplant, according to study findings presented at ASH Annual Meeting and Exposition.
The results are similar to previously reported data on autologous hematopoietic cell transplantation (auto-HCT) in comparison to chimeric antigen receptor T-cell therapy in patients in partial remission, according to researchers.
“This does not disagree or contradict the randomized clinical trials that compare CAR-T to salvage therapy, followed by auto-HCT in the relapse setting,” Mazyar Shadman, MD, MPH, an associate professor in the clinical research division at Fred Hutchinson Cancer Center, told Healio. “We are asking a slightly different question here than clinical trials have asked. We’re not trying to say that auto-HCT is better than CAR-T, but in some patients in the relapse setting who show chemo-sensitive sensitivity, you could consider auto-ACT as another way of potentially curing this disease.”
Background and methodology
Researchers compared the outcome of patients with large B-cell lymphoma (LBCL) who received either CAR-T or auto-HCT while in complete remission.
Study investigators identified 360 patients with LBCL in complete remission prior to receiving CAR-T (n = 79) or auto-HCT (n = 281), with a median follow-up of 24.7 months (range, 3.3–49.4) among patients in the CAR-T cohort and 49.7 months (range, 3–95.4) in the auto-HCT cohort.
Among the 79 patients who had previously received CAR-T, 53% received tisagenlecleucel (also called tisa-cel; Kymriah, Novartis), 46% received axicabtagene ciloleucel (also called axi-cel; Yescarta, Kite Pharma/Gilead Sciences) and 1% received lisocabtagene maraleucel (also called liso-cel; Breyanzi, Bristol Myers Squibb).
PFS and OS served as the study’s primary endpoints, with secondary endpoints comprising treatment-related mortality and relapse rate.
Results, next steps
Univariate analysis showed an association between CAR-T and a higher rate of relapse at 2 years (48% vs. 27.8%), a lower rate of 2-year PFS (47.8% vs. 66.2%) and lower 2-year OS (65.6% vs. 78.9%) compared with patients who received auto-HCT; researchers noted no statistically significant difference in rates of 2-year treatment-related mortality between the two treatments (4.1% vs. 5.9%).
Among patients with early treatment failure (CAR-T = 57 patients; auto-HCT = 163 patients), CAR-T had a higher 2-year relapse rate (45.9% vs. 22.8%) and an inferior 2-year PFS rate (48.3% vs. 70.9%) compared with auto-HCT, with no notable difference in 2-year OS or treatment-related mortality.
Upon multivariate analysis of outcomes, researchers noted CAR-T’s association with a higher risk for relapse (HR = 2.18; P < .0001) and an inferior PFS (HR = 1.83; P = .0011) when compared with auto-HCT, with no difference in risk for treatment-related mortality (HR = 0.59) or OS (HR = 1.44).
Moving forward, Shadman said a similar analysis may be possible within the next 12 to 24 months while factoring for a different CAR-T drug, thus potentially finding more interesting results.
“One of the limitations of this analysis is that a percentage of the patients who received CAR-T received tisa-cel, which isn’t necessarily the best CAR-T product,” Shadman said. “I think a good question is, what if in a year or two, you look at the same question and only include patients who received lisa-cel or axi-cel and then compare the outcomes of CAR-T to auto-HCT. Because in that case, you’re looking at what are probably better CAR-T products and you may find a different answer.”
Perspective
Back to Top
Tycel Phillips, MD
This study is very much the opposite of what we’ve seen in randomized phase 3 studies. I don’t think it invalidates the data. However, we now have two prospective studies that have demonstrated that CAR-T is beneficial over autologous stem cell transplantation in patients with relapsed or refractory large cell lymphoma, yet we also have this retrospective database that looked at outcomes in patients with complete response, comparing those who went on to autologous transplant vs. CAR-T. I wouldn’t say these data are surprising, because a lot of us who haven’t necessarily fully switched over to CAR-T probably feel that there is still some role for autologous stem cell transplantation in those who are sensitive to chemotherapy. However, I’m sure Shadman and colleagues will get some pushback on these results from those who are very much believers in CAR-T in this patient population.
Still, I think this study brings up some key questions that the randomized trials were not designed to answer. If you look at those trials, they report out on patients who actually received the CAR T-cell product, not necessarily every patient who was enrolled into the study but did not make it to CAR-T. That is an important distinction because a fair number of us in clinical practice have patients who we’d like to take to CAR-T but for various reasons — such as logistics, lack of caregiver support, or not enough time from collection to receipt of cells — do not get there. These are issues that we don’t necessarily have to deal with in autologous stem cell transplantation. I think the safest takeaway from this study is that autologous transplant probably shouldn’t be something we completely exclude in patients with relapse, or for large T-cell lymphoma, as second-line CAR-T is a bit of a misnomer. If these patients are responding to chemotherapy, maybe they should just be taken to an autologous transplant and CAR-T should be saved for later.
I think we just need to be a bit more open-minded and not so dogmatic, especially if the patient has a complete response to chemotherapy.
Perspective
Back to Top
Mikkael A. Sekeres, MD
This study really intrigued a lot of us because the findings were counterintuitive. CAR T-cell therapy is biologically and technologically fascinating, and there are patients who really benefit from it. But when you look at longer-term follow-up, most patients will relapse after the first year, so it isn’t a panacea for most patients.
Also, there are some untoward consequences emerging for CAR T-cell therapy. It might not be a high absolute risk, but you don’t want to look a patient in the eye and tell them there’s a chance they can get another cancer from the treatment we’re giving them.
CAR T-cell therapy is not going away, so I think this begs for a prospective randomized trial of autologous transplant vs. CAR-T to see which one really is the winner. And for patients who receive autologous transplant and then have relapsed or refractory lymphoma, there still will be a role for CAR T cells.
Collapse
Shadman M, et al. Abstract 781. Presented at: ASH Annual Meeting and Exhibition; Dec. 9-12, 2023; San Diego.
Read more about
Click Here to Manage Email Alerts